Endogenous gene regulation to treat neurological disorders and diseases

Technical Field

The present invention relates generally to methods and materials involving regulation of endogenous gene regulation to treat neurological disorders and diseases. In some particular cases, the invention relates to CRISPRa-mediated gene therapy for neurological disorders, such as epilepsy.

Background Art

Epilepsy remains one of the most common serious neurological diseases, affecting 1% of the world’s population. Of these sufferers, 30% are refractory to pharmacological treatment. New anti-epileptic drugs have had little impact on refractory epilepsy and people with uncontrolled seizures continue to experience co-morbidities, social exclusion, and a substantial risk of sudden unexpected death in epilepsy (SUDEP). Refractory epilepsy is mostly focal but primary generalized epilepsy can also be resistant to pharmacotherapy.

Although surgical resection of the epileptogenic zone can result in seizure freedom, it is unsuitable for 90% of people with refractory epilepsy. Furthermore, surgery is limited by risk of damage to eloquent regions of the cortex involved in functions such as memory, language, vision or motor control. However, such surgery is unsuitable for many due to risk of damage to eloquent regions of the cortex involved in functions such as memory, language, vision or motor control.

Minimally invasive ablation procedures using lasers have a role in targeting inaccessible deep structures in the brain but are also limited by risk of damage to neighbouring structures. Deep brain stimulation and other neuromodulatory treatments are of limited effectiveness.

Gene therapy is a promising candidate as a rational replacement for surgical treatment of pharmaco-resistant focal epilepsy. However, current experimental gene therapies are based on either the permanent modification of neuronal excitability using exogenous gene delivery (neurotransmitter, ion channel or receptor overexpression) or the exogenous delivery of light or chemicals to achieve on-demand modulation of neuronal activity (optogenetics and chemogenetics). These approaches have several limitations. In particular they are limited by the size of the promoter and transgene that can fit into a viral vector (AAV or lentivector) meaning that only the coding sequence of a single exogenous gene can be included. In the case of some large genes, it is even impossible to include the entire coding sequence. Furthermore, because introns are typically excluded, conventional gene transfer technology does not ensure that the normal splicing of mRNA occurs.

An alternative approach is to use gene therapy to upregulate endogenous genes for a therapeutic effect. There are many endogenous genes that could in principle be harnessed to reduce circuit hyperexcitability in the brain in order to achieve an anti-epileptic effect. Although such an approach would have an application to epilepsy it can be extended to other neurological and psychiatric diseases where the ability to modifying the expression of any desired gene or genes in the genome would represent a game-changing strategy.

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) allow manipulation of endogenous genes and is based on using a nuclease-defective Cas9 protein in combination with one or more synthetic guide RNAs to recruit transcriptional enhancers or suppressors to their regulatory sequences.

This CRISPR-activation (CRISPRa) strategy has been used to decrease neuronal excitability and suppress seizures in a mouse model of acquired focal epilepsy (Colasante, Qiu et al., 2020; doi:10.1093/brain/awaa045). The CRISPRa technology was applied to increase the expression of the endogenous potassium channel gene KCNA1 (encoding Kv1.1) in hippocampal neurons.

CRISPRa can also be used to increase gene expression to rescue haploinsufficiency because it leads to a more graded upregulation than conventional transgene delivery. CRISPRa has been applied to treat a mouse model of severe childhood epilepsy (Dravet syndrome) caused by Senia haploinsufficiency (Colasante, Lignani et al.2019; https://doi.orq/10.1016/i.ymthe.2O19.08.018.)

However, these approaches have thus far only been designed and validated in mice, and effective sgRNAs are poorly conserved between species.

Gene therapy is a promising candidate as a rational replacement for surgical treatment of pharmacoresistant focal epilepsy. Examples include overexpression of neuropeptide Y and Y2 receptors (Woldbye et al, 2010), Kv1.1 overexpression (Wykes et al, 2012; WO2018/229254); chemogenetics using designer receptors exclusively activated by designer drugs (DREADDs), e.g. hM4Di (WO2015/136247). Typically such gene therapies are based on delivery of single genes to modify neuronal excitability. These approaches are limited by the size of the transgene that can fit into the viral vector (AAV or lentivirus) and usually this means that only the coding sequence of a single gene can be included.

WO2021/191474 describes expression vectors or vector systems comprising a polynucleotide sequence encoding a polypeptide, wherein the gene is operably linked to a particular neuronal activity-dependent promoter suitable to drive expression of the gene product in a subject's neural cells. The features of the expression vectors combine to advantageously improve the treatment of a neurological disorder associated with neuronal hyperexcitability in a subject.

Nevertheless it can be seen that providing novel gene therapy approaches that address one or more of the drawbacks of these previous approaches would provide a useful contribution to the art.

Disclosure of the invention

The invention is based on the provision of novel single guide RNAs (“sgRNAs”) comprising RNA targeting one or more endogenous human genes, that are capable of increasing the expression of endogenous human genes involved in neurological diseases and disorders. In some applications these sgRNAs, in combination with a nuclease-defective Cas9 or related enzymes such as Cas12, and a transcriptional activator, offer a novel approach to improved treatment of epilepsy and other neurological diseases, using CRISPRa.

Accordingly, in one aspect, the invention provides a targeting RNA for use in a method of treating a neurological disorder or disease in a human subject, wherein:

(i) the targeting RNA comprises a first targeting nucleic acid sequence with a specificity for a regulatory sequence of a first endogenous human gene associated with the neurological disorder; and

(ii) the method comprises administering to the subject:

(a) single guide RNA (“sgRNA”), the sgRNA comprising the targeting RNA and a CRISPR nuclease binding region (“tracrRNA”); or

(b) tracrRNA and crisprRNA (“crRNA”), the crRNA comprising the targeting RNA and a binding region for the tracrRNA;

(c) a deactivated CRISPR nuclease (“dCas”); and

(d) a transcriptional activator, wherein the (i) sgRNA or (ii) crRNA and tracrRNA form a complex with the dCas and transcriptional activator in a cell of the subject, and increase expression of the first endogenous human gene.

The invention is also based on the provision of a combinatorial gene therapy approach using CRISPRa, to simultaneously increase the expression of multiple endogenous human genes in human subjects, in order to achieve a greater rescue of seizures and behavioural deficits. It is believed that targeting endogenous human genes that act through a different mechanism will further improve the ability to restore physiological brain function. The potential utility of combinatorial gene therapy is further based on several lines of evidence. Firstly, single-gene therapies have not been shown to completely stop seizures in rodent studies. Secondly, gene therapy approaches that have shown partial efficacy in rodents in our group and in others, have targeted several different signalling cascades including neuropeptide signalling, ion channels, chemogenetics and optogenetics. Current experimental gene therapies are typically based on delivery of single genes to modify neuronal excitability.

Accordingly, in another aspect of the invention:

(i) the targeting RNA comprises a second targeting nucleic acid sequence with a specificity for a regulatory sequence of a second endogenous human gene associated with the neurological disorder; and

(ii) the method comprises administering to the subject:

(a) single guide RNA (“sgRNA”), the sgRNA comprising the targeting RNA and a CRISPR nuclease binding region (“tracrRNA”) for each targeting nucleic acid sequence; or

(b) tracrRNA for each targeting nucleic acid sequence and crisprRNA (“crRNA”), the crRNA comprising the targeting RNA and a binding region for a tracrRNA;

(c) a deactivated CRISPR nuclease (“dCas”) for complexing with the targeting nucleic acid sequences; and

(d) a transcriptional activator for complexing with the targeting nucleic acid sequences, wherein the targeting nucleic acid sequences of the (i) sgRNA or (ii) crRNA and tracrRNA form a complex with a dCas and a transcriptional activator in a cell of the subject, and increase expression of the first and second endogenous human genes.

In other aspects, the targeting RNA may further comprise a third, fourth, fifth or higher targeting nucleic acid with a specificity for a regulatory sequences of a third, fourth, fifth or higher endogenous human gene associated with the neurological disorder.

These aspects can finely regulate endogenous gene expression and allow graded upregulation of the potassium channel to reduce seizures.

In some particular cases, the method is a CRISPRa method.

The targeting RNA comprises a targeting nucleic acid sequence with a specificity for a target endogenous human gene. In some cases the targeting RNA, as part of a sgRNA/dCas/activator or crRNA/tracrRNA/dCas/activator complex, binds to the target endogenous human gene and not to off-target endogenous human genes, leading to the preferential alteration of expression of the target endogenous human gene. This may result from direct binding of the complex to the target endogenous human gene, but may also result from binding to a regulatory sequence. Thus, in some particularly preferred cases, the first targeting RNA sequence and second targeting RNA sequence, when present, target a regulatory sequence of the first endogenous human gene and second endogenous human gene respectively, optionally wherein the regulatory sequence is a promoter sequence. The targeting RNA sequences may also target at or near to the proximal promoter of the target human gene, or an enhancer at, near to or far from the target human gene.

The invention also provides a human regulatory sequence for the design of a targeting RNA as disclosed herein, the regulatory sequence consisting of a sequence of any one of SEQ ID NOs: 14-46. The regulatory sequence may be isolated. The invention also provides a targeting RNA comprising a targeting nucleic acid sequence with a specificity for a human regulatory sequence as disclosed herein. In some embodiments, the targeting nucleic acid sequence comprises or consists of a sequence selected from SEQ ID NOs: 1-3, 13, 49-55, 63-65, 69-71 , 75-80, 87-89, 93-95, 99-101 , 105-107, 111-113, and 117-119. In some embodiments, the targeting nucleic acid sequence comprises or consists of (i) a sequence selected from SEQ ID NOs: 1-3, 13, 49-55, 63-65, 69-71 , 75-80, 87-89, 93-95, 99-101 , 105-107, 111-113, and 117-119 and/or (ii) comprises or consists of SEQ ID NO: 1-3, 13, 49-55, 63-65, 69-71 , 75-80, 87-89, 93-95, 99-101 , 105-107, 111-113, and 117-119.

The invention also provides, in other aspects:

• A targeting RNA comprising a first targeting nucleic acid sequence with a specificity for a first endogenous human gene associated with the neurological disorder, wherein the first targeting nucleic acid sequence is encoded by a sequence as disclosed herein.

• A targeting RNA comprising a first targeting nucleic acid sequence with a specificity for a first endogenous human gene associated with the neurological disorder, and a second targeting nucleic acid sequence with a specificity for a second endogenous human gene associated with the neurological disorder, wherein the first and second targeting nucleic acid sequence are separately encoded by a sequence as disclosed herein.

• A crRNA for use in a method of treating a neurological disorder in a human subject, or a crRNA, comprising a targeting RNA as disclosed herein, and a region for complexing to a CRISPR nuclease binding region (“tracrRNA”).

• A guide RNA system for use in a method of treating a neurological disorder in a human subject, or a guide RNA system, comprising a crRNA as disclosed herein.

• A single guide RNA (“sgRNA”) for use in a method of treating a neurological disorder in a human subject, or a sgRNA, comprising a targeting RNA or crRNA as defined herein, and a tracrRNA.

• A composition for use in a method of treating a neurological disorder in a human subject, or a composition, comprising a sgRNA as disclosed herein, a deactivated CRISPR nuclease as disclosed herein, and a transcriptional activator as defined herein, optionally wherein the dCas is fused to the transcriptional activator.

• An expression vector system for use in a method of treating a neurological disorder in a human subject, comprising:

(i) a first vector comprising a polynucleotide sequence encoding a sgRNA as disclosed herein; and either

(ii) a second vector comprising a polynucleotide sequence encoding a deactivated CRISPR nuclease fused to a transcriptional activator as defined herein; or

(iii) a second vector comprising a polynucleotide sequence encoding a deactivated CRISPR nuclease as defined herein, and a third vector comprising a polynucleotide sequence encoding a transcriptional activator as defined herein.

• An expression vector system for use in a method of treating a neurological disorder in a human subject, comprising:

(i) a first vector comprising a polynucleotide sequence encoding a crRNA as disclosed herein;

(i) a second vector comprising a polynucleotide sequence encoding a tracrRNA as defined herein; and either

(iii) a third vector comprising a polynucleotide sequence encoding a deactivated CRISPR nuclease as defined herein fused to a transcriptional activator as defined herein; or

(iv) a third vector comprising a polynucleotide sequence encoding a deactivated CRISPR nuclease as defined herein, and a fourth vector comprising a polynucleotide sequence encoding a transcriptional activator as defined herein.

• An expression vector for use in a method of treating a neurological disorder in a human subject, or an expression vector, comprising:

(i) a polynucleotide sequence encoding a crRNA as defined herein;

(ii) a polynucleotide sequence encoding a tracrRNA as defined herein; and either

(iii) a polynucleotide sequence encoding a deactivated CRISPR nuclease as defined in any one of the above claims fused to a transcriptional activator as defined in any one of the above claims; or

(iv) a polynucleotide sequence encoding a deactivated CRISPR nuclease as defined in any one of the above claims and a polynucleotide sequence encoding a transcriptional activator as defined in any one of the above claims.

• An expression vector system for use in a method of treating a neurological disorder in a human subject, or an expression vector system, comprising:

(i) a first vector comprising a polynucleotide sequence encoding a first sgRNA as defined herein, wherein the targeting RNA only targets a first endogenous human gene;

(ii) a second vector comprising a polynucleotide sequence encoding a second sgRNA as defined herein, wherein the targeting RNA only targets a second endogenous human gene; and either

(iii) a third vector comprising a polynucleotide sequence encoding a deactivated CRISPR nuclease as defined in any one of the above claims fused to a transcriptional activator as defined in any one of the above claims; or

(iv) a third vector comprising a polynucleotide sequence encoding a deactivated CRISPR nuclease as defined in any one of the above claims and a fourth vector comprising a polynucleotide sequence encoding to a transcriptional activator as defined in any one of the above claims.

• An in vitro method of making viral particles comprising (i) transducing mammalian cells with an expression vector or expression vector system as defined herein and expressing viral packaging and envelope proteins necessary for particle formation in the cells; and culturing the transduced cells in a culture medium, such that the cells produce viral particles that are released into the medium.

A kit comprising an expression vector or expression vector system as defined herein and one or more viral packaging and envelope expression vectors that encode viral packaging and envelope proteins necessary for particle formation when expressed in a cell.

A method of treatment of a neurological disorder as defined herein, comprising administering to an individual with the neurological disorder an expression vector or vector system as defined herein.

A method of determining the expression of a first and/or second endogenous human gene as defined herein, comprising (i) transducing a cell with an expression vector or expression vector system as defined herein or administering a viral particle as defined herein to a cell under conditions that permit expression of the first human gene and/or second gene; and (ii) measuring the amount of the expression product of the first human gene and/or second gene, and comparing it to the amount of the expression product of the first human gene and/or second gene in a cell not transduced with expression vector, expression vector system or viral particle.

A cell comprising the expression vector or expression vector system as defined herein.

A targeting RNA system for use in a method of treating a neurological disorder or disease in a human subject as defined herein, wherein:

(i) the targeting RNA system comprises:

(a) a first targeting RNA comprising a first targeting nucleic acid sequence with a specificity for a regulatory sequence of a first endogenous human gene associated with the neurological disorder; and

(b) a second targeting RNA comprising a second targeting nucleic acid sequence with a specificity for a regulatory sequence of a second endogenous human gene associated with the neurological disorder; and

(ii) the method comprises administering to the subject:

(a) a first single guide RNA (“sgRNA”) comprising the first targeting RNA and a CRISPR nuclease binding region (“tracrRNA”) and a second single guide RNA (“sgRNA”), comprising the second targeting RNA and a CRISPR nuclease binding region (“tracrRNA”) or

(b) first tracrRNA and first crisprRNA (“crRNA”), the first crRNA comprising the first targeting RNA and a binding region for a tracrRNA, and second tracrRNA and second crisprRNA (“crRNA”), the second crRNA comprising the second targeting RNA and a binding region for a tracrRNA; and

(c) a deactivated CRISPR nuclease (“dCas”) for complexing with each targeting nucleic acid sequence; and

(d) a transcriptional activator for complexing with each targeting nucleic acid sequence, wherein each sgRNA or crRNA forms a complex with a dCas and a transcriptional activator in a cell of the subject, and increase expression of the first and second endogenous human genes.

Some further aspects and embodiments of the invention will now be discussed in more detail. The following embodiments may be applied in combination with the various targeting RNA, crRNA, sgRNA, guide RNA systems, compositions, expression vectors, expression vector systems, human regulatory sequences, kits, particles and methods of the invention, even if those embodiments are disclosed in the context of particular aspects. CRISPR activation (“CRISPRa”)

As used herein, the term "CRISPR" refers to Clustered Regularly Interspaced Short Palindromic Repeat systems or loci, or a derivative thereof. CRISPR loci can be found in the genomes of many bacteria and archaea. There are four types of CRISPR systems (e.g. , Type I, Type II, Type III, and Type U).

The DNA editor/regulator CRISPR/Cas9 (Konermann et al., 2015; Dominguez et al., 2016; Adli, 2018) represents a powerful tool to modify endogenous genes, not only in somatic cells but also in mammalian neurons (Heidenreich and Zhang, 2016; Suzuki et al., 2016). In addition to permanently altering endogenous gene sequences, CRISPR/Cas9 can regulate the activity of genes through promoter modulation, an approach known as CRISPR activation (CRISPRa) (Dominguez et al., 2016; Liao et al., 2017; Matharu et al., 2019).

The CRISPRa system consists of a nuclease-defective Cas9 (dCas9) fused to a transcription activator and a single guide RNA (sgRNA) that targets dCas9 to the promoter of the target human endogenous gene (Dominguez et al., 2016). The sgRNA comprises targeting RNA of the invention.

There are multiple advantages of this system. First, it is versatile because the targeted gene can be switched by changing the sgRNA. Second, CRISPRa preserves the full range of native splice variants and protein biogenesis mechanisms (Liao et al., 2017). Third, CRISPRa is, in principle, safe because it only alters the promoter activity of genes that are already transcribed in targeted neurons. Finally, CRISPRa can be targeted to specific neurons in the epileptic focus using established viral vectors (La Russa and Qi, 2015).

Targeting nucleic acid sequences

As already mentioned, the targeting RNA comprises a targeting nucleic acid sequence with a specificity for a target endogenous human gene. In some cases this means that the targeting RNA, as part of a sgRNA/cas or crRNA/tracrRNA/cas complex, binds to the target endogenous human gene and not off-target endogenous human genes, leading to the preferential alteration of expression of the target endogenous human gene. This may result from direct binding of the complex to the target endogenous human gene, but may also result from binding to a regulatory sequence. Thus, in some particularly preferred cases, the first targeting RNA sequence and second targeting RNA sequence, when present, target a regulatory sequence of the first endogenous human gene and second endogenous human gene respectively, optionally wherein the regulatory sequence is a promoter sequence. In some preferred embodiments, the first and second targeting RNA sequence are different.

In some embodiments, (i) the first targeting nucleic acid sequence has at least 70, 75, 80, 85, 90, 91 , 92, 93, 94, 95, 96, 97, 98 or 99% sequence identity to a sequence selected from SEQ ID NOs: 1-3, 13, 49-55, 63-65, 69-71 , 75-80, 87-89, 93-95, 99-101 , 105-107, 111-113, and 117-119; and/or (ii) the second targeting nucleic acid sequence, when present, has at least 70, 75, 80, 85, 90, 91 , 92, 93, 94, 95, 96, 97, 98 or 99% sequence identity to SEQ ID NO: 1-3, 13, 49-55, 63-65, 69-71 , 75-80, 87-89, 93-95, 99-101 , 105-107, 111-113, and 117-119. In some embodiments, (i) the first targeting nucleic acid sequence comprises or consists of a sequence selected from SEQ ID NOs: 1-3, 13, 49-55, 63-65, 69-71, 75-80, 87-89, 93-95, 99-101 , 105-107, 111-113, and 117-119; and/or (ii) the second targeting nucleic acid sequence, when present, comprises or consists of SEQ ID NO: 1-3, 13, 49-55, 63-65, 69-71 , 75-80, 87-89, 93- 95, 99-101 , 105-107, 111-113, and 117-119. In some particularly preferred embodiments, the first targeting nucleic acid sequence and second targeting nucleic acid sequence are different.

In some embodiments, (i) the first targeting nucleic acid sequence is encoded by or specifically hybridizes to a nucleic acid sequence that has at least 70, 75, 80, 85, 90, 91 , 92, 93, 94, 95, 96, 97, 98 or 99% sequence identity to a sequence selected from SEQ ID NOs: 1-3, 13-46, 49-122, 124-129, or 131-38; and/or (ii) the second targeting nucleic acid sequence, when present, is encoded by or specifically hybridizes to a nucleic acid sequence that has at least 70, 75, 80, 85, 90, 91 , 92, 93, 94, 95, 96, 97, 98 or 99% sequence identity to a sequence selected from SEQ ID NOs: 1-3, 13-46, 49-122, 124-129, or 131-38. In some embodiments, (i) the first targeting nucleic acid sequence is encoded by or specifically hybridizes to a nucleic acid sequence that comprises or consists of a sequence selected from SEQ ID NOs: 1-3, 13-46, 49-122, 124-129, or 131-38; and/or (ii) the second targeting nucleic acid sequence, when present, is encoded by or specifically hybridizes to a nucleic acid sequence that comprises or consists of a sequence selected from SEQ ID NOs: 1-3, 13-46, 49-122, 124-129, or 131-38.

Alignment and calculation of percentage amino acid or nucleotide sequence identity can be achieved in various ways known to a person of skill in the art, for example, using publicly available computer software such as ClustalW 1.82, T-coffee or Megalign (DNASTAR) software. When using such software, the default parameters, e.g. for gap penalty and extension penalty, are preferably used. The default parameters of ClustalW 1.82 are: Protein Gap Open Penalty = 10.0, Protein Gap Extension Penalty = 0.2, Protein matrix = Gonnet, Protein/DNA ENDGAP = -1 , Protein/DNA GAPDIST = 4.

The percentage identity can then be calculated from the multiple alignment as (N/T)*100, where N is the number of positions at which the two sequences share an identical residue, and T is the total number of positions compared. Alternatively, percentage identity can be calculated as (N/S)*100 where S is the length of the shorter sequence being compared. The amino acid/polypeptide/nucleic acid sequences may be synthesised de novo, or may be native amino acid/polypeptide/nucleic acid sequence, or a derivative thereof.

In general, due to the degeneracy of the genetic code, it is clear that any nucleic acid sequence could be varied or changed without substantially affecting the sequence of a protein encoded thereby, to provide a functional variant thereof. Suitable nucleotide variants are those having a sequence altered by the substitution of different codons that encode the same amino acid within the sequence, thus producing a silent change. Other suitable variants are those having homologous nucleotide sequences but comprising all, or portions of, sequence which are altered by the substitution of different codons that encode an amino acid with a side chain of similar biophysical properties to the amino acid it substitutes, to produce a conservative change.

In some embodiments, the targeting RNA may be generated from a human regulatory sequence as defined herein. Such targeting RNA may be generated by bioinformatic analysis as described in e.g. Colasante 2020. Encyclopedia of DNA Elements (ENCODE) and the Functional ANnoTation of the Mammalian genome (FANTOM) (Carninci et al., 2006) databases may be used to download transcriptomics and epigenetics NGS data for a target endogenous human gene. Tracks can be visualized along the human reference genome with the Integrative Genome Viewer (IGV) (Thorvaldsdottir et al., 2013). Relevant promoter sequences 600bp before the estimated Transcription Starting Site (TSS) can be used to design the sgRNAs with CHOPCHOP (http://chopchop.cbu.uib.no/).

In some embodiments, the targeting RNA comprises a sequence according to any one of the Figures, for Example Figures 16-78. In some aspects, the invention provides a nucleotide comprising or consisting of a sequence that has at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to a sequence selected from SEQ ID NOs: 1-138. sgRNA, guide RNA systems, crRNA and tracrRNA

In some aspects the invention provides sgRNA, guide RNA systems, crRNA that comprise targeting RNA of the invention.

Single guide RNA (“sgRNA”) comprises crRNA (“CRISPR RNA”) and tracrRNA (“trans-activating CRISPR RNA”), and is able to complex with CRISPR nucleases via the tracrRNA region. Guide RNA systems comprise crRNA (“CRISPR RNA”) and tracrRNA (“trans-activating CRISPR RNA”), wherein the crRNA and tracrRNA are not covalently bonded, and is able to complex with CRISPR nucleases via the tracrRNA region. crRNA may comprise targeting RNA of the invention, which may be separated by palindromic repeat sequences. tracrRNA, or “scaffold regions”, enable complexation of crRNA and sgRNA to a CRISPR nuclease. In some embodiments, the scaffold region comprises an ms2, f6, PP7, com, or L7a ligand sequence. In some embodiments, the scaffold region of the guide RNA in a cas complex is bound to a transcriptional activation domain fused to an MCP polypeptide, a COM polypeptide, a PCP polypeptide, or an L7a polypeptide. The tracrRNA can pair with crRNA to form a functional guide RNA, which can complex with a CRISPR nuclease.

The sgRNA may be synthetic sgRNA.

In some cases, the targeting RNA as part of a sgRNA/cas or crRNA/tracrRNA/cas complex targets a target human endogenous gene with 100% efficiency. In some cases, the targeting RNA has at least 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or has 100%, sequence identity to promoter sequence of the target human endogenous gene sequence. The sgRNA or crRNA may be constitutively expressed and operably linked to a separate promoter, such as RNA polymerase III (e.g. U6). The separate promoter may also be any promoter suitable to express sgRNA or crRNA, such as an RNA polymerase, for example RNA polymerase II. The sgRNA and separate promoter may also be comprised by, or separate to, the expression vectors and vector systems disclosed herein. In some cases, the sgRNA or crRNA may also be operably linked to an activity-dependent promoter as disclosed herein, such as cfos, or to an inducible promoter such as Tet-On.

In some cases, the targeting RNA as part of a sgRNA/cas or crRNA/tracrRNA/cas complex targets a target human endogenous gene and causes upregulation of the target human endogenous gene. Upregulation may lead to 2x, 3x, 4x, 5x, 6x, 7x, 8x, 9x or 10x increase in normalised mRNA expression of the target endogenous gene, e.g. as measured by quantitative RT-PCR. In some embodiments, upregulation of the target human endogenous gene is measured as an increase relative to an sgRNA Lac Z control, e.g. SEQ ID NO: 4 or 47. The increase may also be measured relative to SEQ ID NO: 11 , 48, 123 or 130. Other functional activities may be measured as changes relative to these sequences. In some embodiments, this measurement can be performed as follows:

RNA is extracted from primary neurons and cells using TRI ReagentVR (Sigma) according to the manufacturer’s instructions. For quantitative RT-PCR (RT-qPCR), cDNA synthesis is obtained using the ImProm-IITM Reverse Transcription System (Promega) and RT-qPCR is carried out with custom designed oligonucleotides using the Titan HotTaq EvaGreenVR qPCR Mix (BIOATLAS). Analysis of relative expression is performed using the DDCT method, relative to the Ctrl-dCas9A condition. To determine Kenai expression in vivo and for RNA-Seq, RNA is extracted from frozen tissues. For qPCR, DDCT was determined in Ctrl-dCas9A or in Kcna1-dCas9A injected hippocampi relative to contralateral hippocampi in epileptic animals at the end of the recordings.

Upregulation may also be quantified via amount of endogenous human gene product. This may be measured by western blot. In some embodiments, this may be performed as follows: Total neuronal protein extracts are obtained from the lysis of primary neurons by RIPA lysis buffer (150 mM NaCI,

1 %Triton, 0.5% sodium deoxycholate, 0.1% sodium dodecyl sulphate, Tris pH 8.0 50 mM, protease inhibitor cocktail)

2 weeks after infection with the CRISPRa-Kcnal system. Lysates are kept on ice for 30 min by vortexing every 10 min and then centrifuged at 4_C for 5 min at 5000 rpm. Supernatants with solubilized proteins are collected in new tubes and stored at -80°C until use. Western blot analysis is performed using primary antibodies against the endogenous human gene products.

Measurement of off-targets may also be performed by the same methods. Putative off-targets may be predicted as follows:

Using the Galaxy web-tool (https://usegalaxy.org/) two datasets are generated: one containing sgRNA off-target sequences predicted by the CRISPOR web tool (http://crispor.tefor.net) and one containing all the 500-bp genomic regions (NCBI37/mm9) upstream to transcription start sites of annotated transcripts. Intersecting the two datasets, all sgRNA off-target sequences in putative gene promoters are derived. To identify genes regulated by putative promoters, the sequence of the predicted off-targets are aligned by IGV to the reference genome and to transcripts annotated in ENSEMBL database. Validation of expression levels of putative off-target genes was performed by RT- qPCR.

RNA sequencing of targeting RNA and mRNA can be performed as follows:

RNA libraries for both in vitro and in vivo experiments are generated starting from 1 Ig of total RNA extracted from control and sgRNA-dCas9A neurons at 10 DIV. RNA quality is assessed using a TapeStation instrument (Agilent) and only RNA samples with integrity number (RIN) 58 are analysed. For in vitro experiments, RNA is processed according to the Lexogen QuantSeq 3’ mRNA-Seq Library Prep Kit protocol and the libraries are sequenced on an Illumina NextSeq 500 with 75-bp stranded reads at CTGB, Ospedale San Raffaele. Fastq files are aligned to the mouse genome (NCBI37/mm9) with Bowtie2. For in vivo experiments, RNA is processed according to the TruSeq Stranded mRNA Library Prep Kit protocol. The libraries are sequenced on an Illumina HiSeq 3000 with 76 bp stranded reads using Illumina TruSeq technology at Genewiz. Image processing and base calling are performed using the Illumina Real Time Analysis Software. Fastq files are mapped to the mm10 mouse reference genome with the STAR aligner v2.7. Differential gene expression and functional enrichment analyses are performed with DESeq2 and GSEA, respectively. Statistical and downstream bioinformatics analyses are performed within the R environment. Gene expression heat maps are produced with GENE-E (Broad Institute). Data of in vitro and in vivo experiments are deposited in the NCBI Gene Expression Omnibus repository with a GEO ID.

The transcriptional activator

As defined herein, transcriptional activators are protein domains or whole proteins that may be linked to the dCas (e.g. dCas9) or sgRNAs, and that assist in the recruitment of important co-factors as well as RNA Polymerase for transcription of the gene(s) targeted by the system. In order for a protein to be made from the gene that encodes it, RNA polymerase must make RNA from the DNA template of the gene during a process called transcription. Transcriptional activators have a DNA binding domain and a domain for activation of transcription. The activation domain can recruit general transcription factors or RNA polymerase to the gene sequence. Activation domains can also function by facilitating transcription by stalled RNA polymerases, and in eukaryotes can act to move nucleosomes on the DNA or modify histones to increase gene expression. In some embodiments, the transcriptional activator is for complexing with the dCas. In some embodiments, the transcriptional activator is fused to dCas. In other embodiments, the transcriptional activator is bound to the sgRNA, targeting RNA, tracrRNA or crRNA. The transcriptional activator may be any defined herein.

The transcriptional activator, along with dCas, may complex both targeting nucleic acid sequences simultaneously, randomly, or at different times.

The CRISPR nuclease

In some embodiments, the CRISPR nuclease comprises (i) a nuclease domain that has been modified to eliminate nuclease and nicking activity and (ii) a transcriptional activation domain. In some embodiments, the CRISPR nuclease comprises a D10A, H840A S. pyogenes dCas9 ("spdCas9"). In some embodiments, the CRISPR nuclease comprises a S. aureus dCas9 ("sadCas9"). In some embodiments the S. aureus dCas9 comprises one or more mutations in one of the following residues: E782, K929, N968, R1015. In some cases, use of sadCAS9 is advantageous as it can permit all gene elements to be comprised by a single expression vector.

In some cases, the CRISPR nuclease is dCas9 or dCas12.

As used herein, the terms "Cas9," "Cas9 molecule," and the like, refers to a Cas9 polypeptide or a nucleic acid encoding a Cas9 polypeptide. A "Cas9 polypeptide" is a polypeptide that can form a complex with a guide RNA (gRNA) and bind to a nucleic acid target containing a target domain and, in certain embodiments, a PAM sequence. Cas9 molecules include those having a naturally occurring Cas9 polypeptide sequence and engineered, altered, or modified Cas9 polypeptides that differ, e.g., by at least one amino acid residue, from a reference sequence, e.g., the most similar naturally occurring Cas9 molecule. A Cas9 molecule may be a Cas9 polypeptide or a nucleic acid encoding a Cas9 polypeptide. A Cas9 molecule may be a nuclease (an enzyme that cleaves both strands of a double-stranded nucleic acid), a nickase (an enzyme that cleaves one strand of a double-stranded nucleic acid), or a catalytically inactive (or dead) Cas9 molecule. A Cas9 molecule having nuclease or nickase activity is referred to as a "catalytically active Cas9 molecule" (a "caCas9" molecule). A Cas9 molecule lacking the ability to cleave or nick target nucleic acid is referred to as a "catalytically inactive Cas9 molecule" (a "ciCas9" molecule) or a "dead Cas9" ("dCas9").

In certain embodiments, the dCas9 molecule is a S. pyogenes dCas9 variant. In certain embodiments, the dCas9 variant is the EQR variant. In certain embodiments, the dCas9 variant is the VRER variant. In certain embodiments, a dCas9 system comprises a dCas9 molecule, e.g., a dCas9 molecule described herein, e.g., the dCas9 EQR variant or the dCas9 VRER variant. In certain embodiments, the dCas9 molecule is a S. aureus dCas9 variant.

In some embodiments, the dCas comprises a transcriptional activation binding domain, wherein the transcriptional activation binding domain specifically binds a composition comprising one or more transcriptional activation domains. In some embodiments, the dCas is fused to a transcriptional activation domain.

The dCas, along with the transcriptional activator, may complex both targeting nucleic acid sequences simultaneously, randomly, or at different times. The dCas, when fused with the transcriptional activator, may complex both targeting nucleic acid sequences simultaneously, randomly, or at different times.

In some embodiments, the transcriptional activation domain is VP16, VP64 or VP160. The transcriptional activation domain may also be selected from the group consisting of HSFI, VP16, VP64, p65, MyoDI, RTA, SET7/9, VPR, histone acetyltransferase p300, an hydroxylase catalytic domain of a TET family protein (e g., TET1 hydroxylase catalytic domain), LSD1 , CIB1, AD2, CR3, EKLF1 , GATA4, PRVIE, p53, SPI, MEF2C, TAX, and PPARy.

In some embodiments, the dCas is a dCas -VP64 fusion polypeptide. In some embodiments, the dCas is a dCas - VP160 fusion polypeptide. In some embodiments, the dCas is a dCas-VP16 fusion polypeptide.

In some cases, the dCas or dCas-VP64 fusion polypeptide further comprises aptamers that bind to MS2 proteins, which may recruit additional activations domains, e.g. HS1 and p65. In some cases, the transcriptional activator is HS1 or p65. In some cases, the dCas is fused to a repeating peptide array fused with multiple copies of VP64. In some cases, the dCas-VP64 fusion polypeptide further comprises p65 and/or Rta, which work in tandem to recruit transcription factors. In some cases, the dCas is fused to CBP, a histone acetyltransferase domain capable of rearranging chromatin structure. In some cases, any of the fusion polypeptides disclosed herein are further fused to the P65-HSF activation domain.

In certain embodiments, a CRISPR nuclease contains (i.e. , is covalently or non- covalently linked to) one or more additional polypeptides or nucleic acids. For example, the CRISPR nuclease can be fused at an amino or carboxy - terminus to one or more transcriptional activation domain polypeptides, one or more DNA-binding polypeptides, one or more affinity tags (e.g., in complex with one or more affinity tag ligands, such as affinity tag ligand- transcriptional activation domain fusion protein(s)), nuclear localization sequences, or a combination thereof.

In some cases, the CRISPR nuclease is fused to one or more affinity tags. For example, the CRISPR nuclease may be a component of a SunTag. Exemplary SunTags or SunTag components include, without limitation, one or more of the affinity tagged CRISPR nucleases or affinity tag ligands, and fusion proteins thereof, described in WO 2016/011070. In one embodiment, the CRISPR nuclease contains one or more affinity tags that are non-covalently bound to one or more ligand-transcriptional activation domain fusion proteins. In such embodiments, the transcriptional activation domain fused to the affinity tag ligand can be, e.g., one or more of the transcriptional activation domains described herein.

Figure 12 shows a schematic of one embodiment of the invention, whereby a dCas9 is fused to a VP160 transcriptional activation domain, and is complexed to a sgRNA. Complexation to the promoter region of the target endogenous gene leads to increased expression of the target endogenous gene.

Preferred qenes and qene products

In some preferred embodiments, the first endogenous human gene and second endogenous human gene, when present, are selected from the group consisting of: GABRA5, KCNA1, KCNA2, LGI1, KCNC1, KCNMA1, KCNK2, KCNQ2, KCNQ3, KCNJ6, GRM2, GDNF, NPY, NPY2R, GALP, GALR1, PDYN, BDNF, FGF2, GABBR1, GABBR2, GRM3, GRM4, GRM7, GABRR1, GABRR3, OPRK1, OPRM1, OPRD1, OPRL1, KCNJ2, GABRA1, and GABRA2.

In some other preferred embodiments, the first endogenous human gene and second endogenous human gene, when present, are selected from the group consisting of: BDNF, FGF2, GABBR1, GABBR2, GABRA1, GABRA2, GABRA5, GALP, GALR1, GDNF, GRM2, KCNA1, KCNA2, KCNC1, KCNJ2, KCNJ6, KCNK2, KCNMA1, KCNQ2, KCNQ3, LGI1, NPY, NPY2R, OPRD1, OPRK1, OPRL1, OPRM1, and PDYN.

All aspects of the invention encompass use of all combinations of genes disclosed herein as the first endogenous human gene and second endogenous human gene. All aspects of the invention also encompass all combinations of genes disclosed in the preceding two paragraphs as the first endogenous human gene and second endogenous human gene. For example, the first and second endogenous human genes may be, respectively: GABRA5 and KCNA1, GABRA5 and KCNA2, GABRA5 and LGI1 ... KCNA1 and GABRA5, KCNA1 and KCNA2, KCNA2 and LGI1 ... PDYN and OPRL1 or P DY N and OPRM1.

In some preferred embodiments, the first human gene is GABRA5, and optionally the second gene is KCNA1. In some preferred embodiments, the first human gene is KCNQ2, and optionally the second gene is KCNQ3. In some preferred embodiments, the first human gene is KCNA2, and optionally the second gene is LGI1. In some preferred embodiments, the first human gene is KCNQ3, and optionally the second gene is LGI1. In some preferred embodiments, the first human gene is KCNA2, and optionally the second gene is KCNJ2.

In some preferred embodiments, the first endogenous human gene and second endogenous human gene are associated with different mechanisms of action of control of neural activity. By mechanism of action of control of neural activity, it is meant a particular molecular pathway that the gene is implicated in, whose dysfunction may lead to neurological disorders or diseases.

In some preferred embodiments, the first endogenous human gene is associated with action potential inhibition and synaptic vesicle release, and the second endogenous human gene is associated with tonic inhibition. In some particularly preferred embodiments, the first endogenous human gene is GABRA5 and the second endogenous human gene is KCNA1.

In some preferred embodiments, the first endogenous human gene is a subunit of a channel or receptor associated with neuronal excitability or synaptic transmission, and the second endogenous human gene is another subunit of the same channel receptor. In some particularly preferred embodiments, the first endogenous human gene is KCNQ2 and the second endogenous human gene is KCNQ3.

In some preferred embodiments, the first endogenous human gene is associated with decreasing neuronal excitability, and the second endogenous human gene is associated with action potential and vesicle release inhibition. In some particularly preferred embodiments, the first endogenous human gene is KCNJ2 and the second endogenous human gene is KCNA2.

In some preferred embodiments, the first endogenous human gene is a subunit of a channel or receptor associated with decreasing neuronal excitability, and the second endogenous human gene is associated with decreasing synaptic transmission. In some particularly preferred embodiments, the first endogenous human gene is KCNQ3 and the second endogenous human gene is LGI1.

GABRA5 encodes the alpha5 subunit of GABAA receptors that contribute to tonic inhibition, which are downregulated in epileptic animals both before and after the therapy. Loss of function GABRA5 mutations have been associated with severe epileptic encephalopathies (Butler et al 2018; Hernandez et al. 2019). Targeting of GABRA5 in combination with KCNA1 is particularly preferred because Gabra5 was found to be downregulated in a rodent model of epilepsy and not rescued by a first-pass CRISPRa approach targeting Kenai alone. alpha5 GABAA receptors have a different mechanism of action than Kv1.1 , encoded by KCNA1, which regulates action potential initiation and synaptic vesicle release (Vivekananda et al 2017).

KCNA1 encodes the Kv1.1 potassium channel which is a voltage-gated delayed-rectifier potassium channel that is phylogenetically related to the Drosophila Shaker channel. Voltage-dependent potassium channels modulate excitability by opening and closing a potassium-selective pore in response to voltage. In many cases, potassium ion flow can be interrupted when an intracellular particle occludes the pore, a process known as fast inactivation. Kv1 potassium channel subunits have six putative transmembrane segments, and the loop between the fifth and sixth segment of each of the four Kv1 subunits that make up a complete channel forms the pore.

In other embodiments, the gene encodes another protein that affects neuronal excitability or neurotransmitter release, including other potassium channels such as Kv1.2, or neurotransmitter receptors such as GABAA or GABAB receptors, adenosine A1 receptors, and NPY Y2 or Y5 receptors, or neuropeptides such as galanin, NPY or dynorphin.

In some preferred embodiments, the gene is defined in the claims as KCNJ2. KCNJ2 encodes the inward-rectifying potassium chancel Kir2.1 , which is normally expressed in skeletal muscle. Kir2.1 contributes to maintaining a negative resting membrane potential, thus reducing intrinsic excitability.

In some preferred embodiments, the gene is defined in the claims as KCNQ2 or KCNQ3. They encode subunits of the voltage-gated potassium channel Kv7. Heterodimers of these subunits showed an 11-fold greater potassium current than either homomeric channel (Barrese et al. 2018). Kv7 is activated at subthreshold potentials and therefore contributes to maintaining the membrane potential of neurons near the resting value, and consequently reducing intrinsic neuronal excitability (Shah et al. 2008).

KCNA2 encodes the Kv1 .2 potassium channel, which is a delayed rectifier voltage-gated potassium channel. Kv1 .2 maintains the resting membrane potential and, consequently, reduces neuronal excitability. Kv1.2 subunits can co- assemble with other Kv1 subunits.

LGI1 encodes LG11 , a secreted synaptic protein which reduces network excitability (Lugara et al. 2019). Loss-of- function mutations cause human partial epilepsy. LGI1 regulates the activity of voltage-gated potassium channels including those consisting of Kv1.1 and Kv1.2 subunits.

In some embodiments, the first and/or second human endogenous gene is implicated in diseases associated with haploinsufficiency, such as SIM1 , Leptin, Leptin receptor, MC4R, SCN2A, SETD5, PAX6, PKD1 , MC3R, POMC, STAT 3, STAT5, SOCS3, GHR, NPY, NPY1 R, NPY2R, NPY5R, PYY, AMPK (PRKAAI, PRKAA2, PRKAB1, PRKAB2, PRKAG1, PRKAG2, PRKAG3), OXT, JAK2, SHP2, NOS3, NROB2, BRS3, CARTPT, FABP4, HTR2C, IL6, NHLH2, NMU, NPB, NPBWRI, PNPLA2, UCP3, ADIPOQ, APOA5, ARNT2, ASIP, C1QTNF2, C3AR1 , CCK, CPT1 B, CSF2, DGAT1 , DGAT2, GHRL, GHSR, HSDIIBI, HTR7, INSIGI, INSIG2, LIPC, NMURI, NMUR2, NPBWR2, NTS, PPARGCIA, PPY, RETN, SIRT1 , TGFBR2, WDTC1 , or FOXOI.

In some embodiments, the regulatory sequence of said genes is a regulatory sequence consisting of a sequence of any one of SEQ ID NOs: 14-46. Expression vectors and vector

In some aspects the invention provides expression vectors and expression vector systems that comprise targeting RNA of the invention.

An expression vector as used herein is a DNA molecule used to transfer and express foreign genetic material in a cell. Such vectors include a promoter sequence operably linked to the gene encoding the protein to be expressed. "Promoter" means a minimal DNA sequence sufficient to direct transcription of a DNA sequence to which it is operably linked. "Promoter" is also meant to encompass those promoter elements sufficient for promoter-dependent gene expression controllable for cell type specific expression; such elements may be located in the 5' or 3' regions of the native gene. Alternatively, an expression vector may be an RNA molecule that undergoes reverse transcription to DNA as a result of the reverse transcriptase enzyme. In some cases, the promoter is modified to allow for incorporation of the first and second targeting RNA sequences, and optionally the deactivated CRISPR nuclease, into a single expression vector. The promoter may be CaMKII, CMV, or any other promoter suitable to drive expression of one or more genes comprised by the expression vector. Each gene comprised by the expression vector may be operably linked to a suitable promoter, or all genes comprised by the expression vector may be operably linked to a single suitable promoter.

An expression vector may also include a termination codon and expression enhancers. Any suitable vectors, enhancers and termination codons may be used to express the gene products. Suitable vectors include plasmids, binary vectors, phages, phagemids, viral vectors and artificial chromosomes (e.g. yeast artificial chromosomes or bacterial artificial chromosomes). As described in more detail below, preferred expression vectors include viral vectors such as AAV vectors.

An expression vector may additionally include a reporter gene encoding a reporter protein. An example of a reporter protein is a green fluorescent protein (“GFP”). A reporter gene may be operably linked to its own promoter or, more preferably, may be operably linked to the same promoter as the gene product as defined in the invention. As an example, the KCNA1 gene and reporter gene may be located either side of a sequence encoding a 2A peptide, such as a T2A peptide. 2A peptides are short (—20 amino acids) sequences that permit multicistronic gene expression from single promoters by impairing peptide bond formation during ribosome-mediated translation (Szymczak and Vignali, 2005). Having the reporter gene operably linked to the same promoter as the gene product, is thought to act as a reliable indicator of gene product expression. An expression vector including a reporter gene may be particularly useful in preclinical applications, for example for use in animal models where it can be used to help assess the localisation of gene expression. The gene encoding GFP may be GFP, dsGFP or dscGFP.

In other embodiments, the expression vector lacks a sequence encoding a reporter protein. This may be preferred for regulatory reasons, for example. In embodiments of the invention, reporting or detecting the gene product of the disclosure may be achieved in different ways - for example based on its engineered sequence. In some embodiments, the expression vector lacks a sequence encoding GFP and/or a sequence encoding a 2A peptide, such as a T2A peptide.

Generally speaking, those skilled in the art are well able to construct vectors and design protocols for recombinant gene expression. Suitable vectors can be chosen or constructed, containing, in addition to the elements of the invention described above, appropriate regulatory sequences, including promoter sequences, terminator fragments, polyadenylation sequences, marker genes and other sequences as appropriate. Molecular biology techniques suitable for the expression of polypeptides in cells are well known in the art. For further details see, for example, Molecular Cloning: a Laboratory Manual: 2nd edition, Sambrook et al, 1989, Cold Spring Harbor Laboratory Press or Current Protocols in Molecular Biology, Second Edition, Ausubel et al. eds., John Wiley & Sons, (1995, and periodic supplements).

The term “operably linked” used herein includes the situation where a selected gene and promoter are covalently linked in such a way as to place the expression of the gene (i.e. polypeptide coding) under the influence or control of the promoter. Thus, a promoter is operably linked to a gene if the promoter is capable of effecting transcription of the gene into RNA in a cell. Where appropriate, the resulting RNA transcript may then be translated into a desired protein or polypeptide. The promoter is suitable to effect expression of the operably linked gene in a mammalian cell. Preferably, the mammalian cell is a human cell.

In some embodiments, the vector or vector system is a viral vector or vector system, optionally wherein the viral vector or vector system is a recombinant adeno-associated virus (AAV) vector or vector system, or a lentiviral vector or vector system, optionally wherein the lentiviral vector or vector system is a non-integrating lentiviral vector or vector system.

In some embodiments, either:

(i) the polynucleotide sequence encoding the crRNA or sgRNA is operably linked to an RNA polymerase III promoter, optionally a U6 promoter; or

(ii) the polynucleotide sequence encoding the first and second sgRNAs are, separately or collectively, operably linked to an RNA polymerase III promoter, optionally a U6 promoter.

In some embodiments, the polynucleotide sequence encoding the CRISPR nuclease is operably linked to an EF-1a promoter or CMV promoter. In some embodiments, the polynucleotide sequence encoding the CRISPR nuclease is operably linked to a CaMKII promoter.

In some embodiments, the expression vector or expression vector system for use comprises a nucleotide sequence having at least 70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% sequence identity to a sequence selected from SEQ ID NOs: 6 and 8-10. In some embodiments, the expression vector or expression vector comprises a nucleotide sequence comprising or consisting of a sequence selected from SEQ ID NOs: 6, 8-10, 56-62, 72-74, 81- 86, 90-92, 96-98, 102-104, 108-110, 114-116, 120-122, 124-129, or 131-138. The expression vector encoding the dCas may comprise or consist of a nucleotide sequence SEQ ID NO: 12.

The elements encoding the sgRNA and CRISPR nuclease may be comprised by the same or different vectors. The elements encoding the crRNA, tracrRNA and the CRISPR nuclease may be comprised by the same or different vectors. The elements encoding the sgRNA for a first target human endogenous gene, the sgRNA for a second target human endogenous gene, and the CRISPR nuclease may be comprised by the same or different vectors. The elements encoding the sgRNA for a first target human endogenous gene and the sgRNA for a second target human endogenous gene may be comprised by the same vector, and the CRISPR nuclease may be comprised by a different vector. The elements encoding the crRNA for a first target human endogenous gene, crRNA for a second target human endogenous gene, tracrRNA, and the CRISPR nuclease may be comprised the same or different vectors. In such cases the promoter may be adapted to allow for the incorporation of the elements into a single vector, such as by modifying its size, e.g. making it smaller.

The promoter may be a neuronal activity-dependent promoter which is a promoter that alters or drives expression of a target gene in response to changes in neuronal activity in neural cells. Such changes in neuronal activity may result from a neural cell that becomes hyperexcited, for example during a seizure. In some preferred embodiments, the neuronal activity-dependent promoter is an immediate early gene (IEG) promoter. In other embodiments, the activity-dependent promoter is cFos, Egr1 (also known as Zif268), Arc, mArc, Homerla, Bdnf, Creb, Srf, Mef2, Fosb, and Npas4 or synthetic activity-dependent promoters such as PRAM (S0rensen et al., eLife 2016) and ESARE (Kawashima et al., Nature Methods 2013 PMID: 23852453), or part of them or combinations of the above. In other embodiments, the activity-dependent promoter is PRAM (Promoter Robust Activity Marker) or parts of this synthetic promoter: NRAM (NPAS4 Robust Activity Marker) or FRAM (Fos Robust Activity Marker).

Expression of a gene product may be achieved via an expression system, such as an inducible expression system. Such expression systems are, in a general sense, known in the art, and may be appropriately selected by the skilled person in order to optimise expression of the intermediate gene or further gene. For example, the expression system may be an inducible expression system such as Tet-On. See e.g. Gaia Colasante et. al (Brain, Volume 143, Issue 3, March 2020, Pages 891-905, https://doi.org/10.1093/brain/awaa045), the contents of which is incorporated herein by reference in its entirety.

Of the currently available inducible gene expression systems, Tet-On is the most widely characterised. In some embodiments, in order to improve brain penetration and reduce side-effects in human subjects, the intermediate inducible gene expression system may be a “GeneSwitch™” system. “GeneSwitch™”, uses a chimeric protein, consisting of a truncated human progesterone receptor that does not respond to endogenous steroids, along with a Gal4 DNA binding domain and a P65 activation domain. The receptor is activated by mifepristone, which frees the complex from co-repressors and allows it to initiate transcription of the desired gene in the nucleus by binding to an upstream activating sequence (UAS).

The expression system can also comprise expression of a modified ecdysone receptor that regulates an optimized ecdysone responsive promoter. The expression systems can also be based on cumate-induced binding of the cumate repressor to the cumate operator, rapamycin-induced interaction between FKBP12 and FRAP, FKCsA- induced interaction between FKBP and cyclophilin, ABA induced interaction between PYL1 and AB11 , and the “riboswitch” system. (Kallunki et al PMC6721553).

Expression vectors may be generated in the following exemplary protocols (as well as those provided in the Examples below):

Small guide RNAs are cloned into a lentiviral vector with a U6 promoter (pU6). Defective Cas9 fused to the VP160 activator domain is cloned into T2A with the Puromucin resistance cassette (PuroR) and under the control of the Eef1a1 (Eflalpha) promoter (Ef1alpha-dCas9VP160-T2APuroR). The dCas9VP160-2A-PuroR assette is obtained from pAC94-pmax-dCas9VP160-2A-PuroR (Addgene plasmid #48226), and subcloned in a the TetO-FUW vector followed by restriction digestion with Hpal/Afel, then blunt cloned into an Ef1alpha-GFP vector after GFP removal by Smal/EcoRV digestion. Ef1alpha-dCas9VP160-T2A-GFP is obtained by restriction digestion of Eflalpha- dCas9VP160-T2APuro R with Ascl/Xbal, which removed VP160-T2A-PuroR; the VP160-T2A fragment is then obtained by Ascl/Xhol digestion from Ef1alpha-dCas9VP160-T2A-PuroR while the GFP fragment is PCR amplified using primers containing Xhol/Xbal restriction sites; the two fragments are then ligated together into the vector.

To obtain a single vector containing both dCas9A and sgRNA, the pU6-sgRNA cassette is Hpal digested and cloned into Ef1alpha-dCas9VP160. To generate an adeno-associated virus (AAV) with activating dCas9 (dCas9-VP64) under a doxycycline-inducible promoter, and tetracycline transactivator responsive element (TRE), AAV-SpCas9 is used as the starting material: the Mecp2 is removed by Xbal/Agel digestion and the TRE promoter was amplified using primers. SpCas9 is removed using Agel/EcoRI and Cas9m4-VP64 is digested with Agel/EcoRI. The VP64 fragment is PCR-amplified using primers. The AAV vector containing the sgRNA cassette is derived from pAAV- U6sgRNA(Sapl)_hSyn-GFP-KASH-bGH. The sgRNA or control are cloned under the U6 promoter and the GFP is removed by Kpnl/Clal digestion and replaced by a DIO-rtTA-T2A-Tomato cassette. Viral vectors

A preferred expression vector for use with the present invention is a viral vector, such as a lentiviral or AAV vector.

In some instances, the vector is a recombinant AAV vector. AAV vectors are DNA viruses of relatively small size that can integrate, in a stable and site-specific manner, into the genome of the cells that they infect. They are able to infect a wide spectrum of cells without inducing significant effects on cellular growth, morphology or differentiation. The AAV genome has been cloned, sequenced and characterized. It encompasses approximately 4700 bases and contains an inverted terminal repeat (ITR) region of approximately 145 bases at each end, which serves as an origin of replication for the virus. The remainder of the genome is divided into two essential regions that carry the encapsidation functions: the left-hand part of the genome, that contains the rep gene involved in viral replication and expression of the viral genes; and the right-hand part of the genome, that contains the cap gene encoding the capsid proteins of the virus.

AAV vectors may be prepared using standard methods in the art. Adeno-associated viruses of any serotype are suitable (see, e.g., Blacklow, pp. 165-174 of "Parvoviruses and Human Disease" J. R. Pattison, ed. (1988); Rose, Comprehensive Virology 3:1 , 1974; P. Tattersall "The Evolution of Parvovirus Taxonomy" in Parvoviruses (J R Kerr, S F Cotmore. M E Bloom, R M Linden, C R Parrish, Eds.) p5-14, Hudder Arnold, London, UK (2006); and D E Bowles, J E Rabinowitz, R J Samulski "The Genus Dependovirus" (J R Kerr, S F Cotmore. M E Bloom, R M Linden, C R Parrish, Eds.) p15-23, Hudder Arnold, London, UK (2006), the disclosures of which are hereby incorporated by reference herein in their entireties). Methods for purifying for vectors may be found in, for example, U.S. Pat. Nos. 6,566, 118, 6,989,264, and 6995006 and International Patent Application Publication No.: W0/1999/011764 titled "Methods for Generating High Titer Helper-free Preparation of Recombinant AAV Vectors", the disclosures of which are herein incorporated by reference in their entirety.

Preparation of hybrid vectors is described in, for example, PCT Application No. PCT/US2005/027091. The use of vectors derived from the AAVs for transferring genes in vitro and in vivo has been described (See e.g., International Patent Application Publication Nos: WO 1/18088 and WO 93/09239; U.S. Pat. Nos. 4,797,368, 6,596,535, and 5,139,941 ; and European Patent No: 0488528). These publications describe various AAV-derived constructs in which the rep and/or cap genes are deleted and replaced by a gene of interest, and the use of these constructs for transferring the gene of interest in vitro (into cultured cells) or in viva (directly into an organism). The replication defective recombinant AAVs according to the invention can be prepared by co-transfecting a plasmid containing the nucleic acid sequence of interest flanked by two AAV inverted terminal repeat (ITR) regions, and a plasmid carrying the AAV encapsidation genes (rep and cap genes), into a cell line that is infected with a human helper virus (for example an adenovirus). The AAV recombinants that are produced are then purified by standard techniques.

In some instances, useful AAV vectors for the expression constructs as described herein include those encapsidated into a virus particle (e.g. AAV virus particle including, but not limited to, AAV1 , AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10, AAV11 , AAV12, AAV13, AAV14, AAV15, AAV16 and AAVrhIO). Accordingly, the instant disclosure includes a recombinant virus particle (recombinant because it contains a recombinant polynucleotide) comprising any of the vectors described herein.

In some embodiments, the viral vector contains a sequence encoding a reporter protein, such as a fluorescent protein. In other embodiments the viral vector lacks a sequence encoding a reporter protein, such as a fluorescent protein. In some embodiments, the viral vector additionally comprises genes encoding viral packaging and envelope proteins.

In some embodiments, the viral vector is a lentiviral vector. In some embodiments, the lentiviral vector is a non- integrating lentiviral vector (NILV). Vector particles produced from these vectors do not integrate their viral genome into the genome of the cells and therefore are useful in applications where transient expression is required or for sustained episomal expression such as in quiescent cells. NILVs can be developed by mutations in the integrase enzyme or by altering the 5’ LTR and/or the 3’ LTR to prevent integrase from attaching these sequences. These modifications eliminate integrase activity without affecting reverse transcription and transport of the pre-integration complex to the nucleus. Without wishing to be bound by any particular theory, when a NILV enters a cell the lentiviral DNA is expected to remain as remains in the nucleus as an episome, leading to sustained expression in non-dividing cells (post-mitotic cells) such as neurons.

In some embodiments, the vector further comprises an AmpR gene, and/or a hGh poly(A) signal gene, and/or one or more origin of replication genes.

In some embodiments, the viral vector comprises a nucleotide sequence having at least 70, 75, 80, 85, 90, 91 , 92, 93, 94, 95, 96, 97, 98 or 99% identity to the nucleotide sequence of SEQ ID NO: 6 and 8-10. In some embodiments, the viral vector is the nucleotide sequence of SEQ ID NO: 6 and 8-10. In some embodiments, the viral vector comprises a nucleotide sequence having at least 70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99% identity to the nucleotide sequence of SEQ ID NO: 6, 8-10, 56-62, 72-74, 81-86, 90-92, 96-98, 102-104, 108-110, 114-116, 120- 122, 124-129, or 131-138. In some embodiments, the viral vector is the nucleotide sequence of SEQ ID NO: 6, 8-10, 56-62, 72-74, 81-86, 90-92, 96-98, 102-104, 108-110, 114-116, 120-122, 124-129, or 131-138.

Viral particles

The invention also includes in vitro methods of making viral particles, such as lentiviral particles or adeno-associated viral particles. In one embodiment, this method involves transducing mammalian cells with a viral vector or expression vector or expression vector system as described herein and expressing viral packaging and envelope proteins necessary for particle formation in the cells and culturing the transduced cells in a culture medium, such that the cells produce viral particles that are released into the medium. An example of a suitable mammalian cell is a human embryonic kidney (HEK) 293 cell.

It is possible to use a single expression vector that encodes all the viral components required for viral particle formation and function. Most often, however, multiple plasmid expression vectors or individual expression cassettes integrated stably into a host cell are utilised to separate the various genetic components that generate the viral vector particles.

In some embodiments, expression cassettes encoding the one or more viral packaging and envelope proteins have been integrated stably into a mammalian cell. In these embodiments, transducing these cells with a viral vector described herein is sufficient to result in the production of viral particles without the addition of further expression vectors.

In other embodiments, the in vitro methods involve using multiple expression vectors. In some embodiments, the method comprises transducing the mammalian cells with one or more expression vectors encoding the viral packaging and envelope proteins that encode the viral packaging and envelope proteins necessary for particle formation. Examples of suitable viral packaging and envelope proteins and expression vectors encoding these proteins are commercially available and well known in the art. In general, the viral packaging expression vector or expression cassette expresses the gag, pol, rev, and tat gene regions of HIV-1 which encode proteins required for vector particle formation and vector processing. In general, the viral envelope expression vector or expression cassette expresses an envelope protein such as VSV-G. In some cases, the packaging proteins are provided on two separate vectors - one encoding Rev and one encoding Gag and Pol. Examples of lentiviral vectors along with their associated packaging and envelope vectors include those of Dull, T. et al., "A Third-generation lentivirus vector with a conditional packaging system" J. V/ra/ 72(11 ):8463-71 (1998).

The ssDNA AAV genome contains two open reading frames, Rep and Cap, flanked by two 145 base inverted terminal repeats (ITRs) fundamental for the synthesis of the complementary DNA strand. Rep and Cap produce multiple proteins (Rep78, Rep68, Rep52, Rep40, which are required for the AAV life cycle; and VP1 , VP2, VP3, which are capsid proteins). The transgene will be inserted between the ITRs and Rep and Cap in trans. An AAV2 backbone is commonly used and is described in Srivastava et al., J. Virol., 45: 555-564 (1983). Cis-acting sequences directing viral DNA replication (ori), packaging (pkg) and host cell chromosome integration (int) are contained within the ITRs. AAVs also require a helper plasmid containing genes from adenovirus. These genes (E4, E2a and VA) mediate AAV replication. An example of a pAAV plasmid is available from Addgene (Cambridge, MA, USA) as plasmid number 112865 or 60958.

Following release of viral particles, the culture medium comprising the viral particles may be collected and, optionally the viral particles may be separated from the culture medium. Optionally, the viral particles may be concentrated.

Following production and optional concentration, the viral particles may be stored, for example by freezing at -80°C ready for use by administering to a cell and/or use in therapy.

The invention also provides viral particles, for example those produced by the methods described herein. As used herein, a viral particle comprises a DNA or RNA genome packaged within the viral envelope that is capable of infecting a cell, e.g. a mammalian cell. A viral particle may be integrase deficient, e.g. it may contain a mutant integrase enzyme or contain alterations in the 5’ and/or 3’ LTRs as described herein.

Virus particles may be prepared as follows: Lentiviruses are produced as previously described with a titre of 10 ⁷ — 10 ⁸ lU/ml (Colasante et al., 2015). AAVs are produced as previously described with a titre 41012 vg/ml (Morabito et al., 2017). The TRE-dCas9-VP64 AAV may be produced by VectorBuilder with a titre of 8x1012 vg/ml.

Virus particles may be transfected into target cells as follows: P19 cells are cultured in alpha-MEM (Sigma-Aldrich) supplemented foetal bovine serum non-essential amino acids, sodium pyruvate, glutamine and penicillin/streptomycin and split every 2-3 days using 0.25% trypsin. For transfection, LipofectamineTM 3000 (Thermo Fisher Scientific) is used according to the manufacturer’s instructions.

Virus particles may also be transfected into target cells as follows: cortical neurons are isolated from postnatal Day 0 C57BI/6J mouse pups as previously described (Beaudoin et al., 2012) and transduced with lentiviruses at 1 day in vitro (DIV). Quantitative RT-PCR, RNA seq, western blot analysis and electrophysiology recordings may be performed 14-16 days after transduction.

Neurological Diseases and Disorders

One aspect the invention provides targeting RNA, crRNA, guide RNA systems, sgRNA, expression vectors and expression vector systems for use in a method of treatment of a neurological disease or disorder in a subject. In certain aspects, the invention also provides the use of the inventive products as described herein for the manufacture of a medicament for the treatment of said neurological diseases or disorders of a subject. The invention also provides methods of treatment of said neurological diseases and disorders which comprise administering the inventive products described herein to an individual in need thereof.

In preferred cases, the subject is a human subject. The subject may also be an animal such as a mouse or a rat.

The disorder may be associated with neuronal hyperexcitability in a subject. Said methods of treatment may be prophylactic.

The neurological disorders as described herein may be associated with neuronal hyperexcitability. As used herein, “hyperexcitability” is a characteristic feature of epilepsy in which the likelihood that neural networks become hypersynchronized, with excessive neuronal firing, is increased. The underlying mechanisms are incompletely understood and may include loss of inhibitory neurons, such as GABAergic interneurons, that would normally balance out the excitability of other neurons, or changes in the intrinsic properties of excitatory neurons that make them more likely to fire abnormally. Among other possible mechanisms are that the levels of GABA and the sensitivity of GABAA receptors to the neurotransmitter may decrease, resulting in less inhibition.

The neurological disorders as described herein may also be associated with haploinsufficiency, and methods may rescue haploinsufficiency in a subject.

Non-limiting examples of neurological disorders associated with neuronal hyperexcitability include seizure disorders (such as epilepsy), Alzheimer's disease, multiple sclerosis, Parkinson's disease, tremor and other movement disorders, chronic pain, migraine, major depression, bipolar disorder, anxiety, and schizophrenia. In particularly preferred embodiments, the treatment is for epilepsy, for example idiopathic, symptomatic, and cryptogenic epilepsy. In particularly preferred embodiments, the epilepsy is neocortical epilepsy or temporal lobe epilepsy, especially if it is resistant to drugs used at therapeutic concentrations (pharmacoresistant or refractory epilepsy). In some embodiments, the epilepsy is acquired focal epilepsy.

In some particularly preferred embodiments, KCNQ2 and KCNQ3, LGI1 and KCNA1, and combinations thereof, are useful in treating epilepsy. In some particularly preferred embodiments, KCNA1 and KCNJ2, KCNQ2 and KCNQ3, and combinations thereof, are useful in treating pain, such as chronic neuropathic pain or primary cephalalgia.

In some preferred embodiments, the neurological disorder is a disorder characterized by episodes of abnormal cellular activity, such as migraine, cluster headache, trigeminal neuralgia, post-herpetic neuralgia, paroxysmal movement disorders, uni- or bipolar affective disorders, anxiety and phobias. In some such disorders (migraine in particular), the abnormal activity may result in neuronal depolarization and electrical silence known as cortical spreading depolarization or cortical spreading depression, and this phenomenon has been implicated in sudden unexpected death in epilepsy (SUDEP).

The treatments described herein may be used to quench or block epileptic activity. The treatments may be used to reduce the frequency of seizures.

In some embodiments, the vector does not affect spontaneous locomotion or memory in a subject, optionally wherein spontaneous locomotion or memory is measured using an open field test, object localisation test, or T maze test. In some embodiments, the expression vectors are only locally active in the seizure focus of the brain of a subject. In some cases, the expression vectors are only locally active in neurons capable of driving a seizure and/ generating sustained firing. In some cases, the expression vectors are only locally active in over-depolarised neurons. In such cases, expression of the sgRNA and/or CRISPR nuclease may be controlled by an activity-dependent promoter.

In some embodiments, the vector or vector system can cause a reduction in the spike frequency of a neuron of the subject by more than 75%. The reduction in the spike frequency of the neuron can be measured using multi- electrode arrays on or after 21 DIV (days in vitro). The reduction in the spike frequency may also be measured using calcium imaging or extracellular field potential recordings on or after 21 DIV. The reduction in the spike frequency of the neuron is measured relative to a control vector. In some cases, the neuron is a primary cortical neuron.

In some embodiments, the vector or vector system can cause fewer than 10 action potentials per second, or fewer than 5 action potentials per second, or fewer than 4 action potentials per second, or fewer than 3 action potentials per second, or fewer than 2 action potentials per second, or no action potentials per second, in a neuron. In some embodiments, the vector or vector system can cause a greater than 50%, greater that 55%, greater that 60%, greater that 65%, greater that 70%, greater that 75%, greater that 80%, greater that 85%, greater that 90%, greater that 95%, or 100% reduction in action potentials per second. The number of action potentials may be measured using ex vivo acute hippocampal slice electrophysiology.

In some embodiments, the vector or vector system can cause a resting membrane potential in a neuron of less than - 50 mV, or less than -60 mV, or less than -70 mV, or less than -80 mV, or less than -90 mV, or less than -100 mV. In some embodiments, the vector or vector system can increase the threshold for action potentials in a neuron to more than 50 pA, or more than 75 pA, or more than 100 pA, or more than 150 pA, or more than 200 pA, or more than 250 pA, or more than 300 pA, or more than 350 pA, or more than 400 pA, or more than 450 pA, or more than 500 pA, or more than 550 pA, or more than 600 pA, or more than 700 pA, or more than 800 pA, or more than 900 pA, or more than 1000 pA, wherein the threshold is the sum of current threshold and holding current.

In some embodiments, the vector or vector system can cause less than 5 spikes/second in a primary neuronal culture grown on multi-electrode arrays (MEAs), as described in the examples. Spike is defined as aggregate neuronal activity. In some embodiments, the vector or vector system can cause less than 10, or less than 5 bursts /minute in a primary neuronal culture grown on MEAs, as described in the examples. In some embodiments, the vector or vector system can cause burst durations of less than 200 msec in a primary neuronal culture grown on MEAs, as described in the examples. In some embodiments, the vector or vector system can cause a mean number of spikes per burst of less than 20, or less than 15 in a primary neuronal culture grown on MEAs, as described in the examples.

In some embodiments, the number of action potentials, resting membrane potential, or threshold for action potentials is measured in an acute hippocampal slice from a subject. In some embodiments, the number of action potentials, resting membrane potential, or threshold for action potentials is measured using acute hippocampal slice electrophysiology and/or patch clamp electrophysiology.

In some cases, the vector or vector system can cause a change as described above, that is improved relative to a reference sequence comprising SEQ ID NO: 4, 11, 47, 48, 123 or 130. In some cases, the vector or vector system can cause a change as described above, that is improved relative to a reference sequence comprising any of SEQ ID NO: 1-138.

To determine efficacy of treatment in model systems, the following exemplary protocols may be used. Slice preparation: Camk2a-Cre mice of either sex (2-3 months old) are sacrificed by cervical dislocation under isoflurane. Brains are quickly dissected into ice-cold oxygenated slicing solution (in mM: 75 sucrose, 2.5 KCI, 25 NaHCO3, 25 glucose, 7 MgCI2, 0.5 CaCI2) and cut into 300 mm coronal slices using a Leica VT1200S vibratome (Leica). Slices are stored submerged in oxygenated recording artificial CSF (in mM: 25 glucose, 125 NaCI, 2.5 KCI, 25 NaHCO3, 1 MgCI2 , 1 .25 NaH2PO4.H2O and 2 CaCI2) at 32_C for 30 min and at room temperature for a further 30 min before recording.

Electrophysiology (In vitro): For current-clamp recordings, the internal solution contains (in mM): 126 K-gluconate, 4 NaCI, 1 MgSO4, 0.02 CaCI2, 0.1 BAPTA, 15 glucose, 5 HEPES, 3 ATP-Na2, 0.1 GTP-Na, pH 7.3. The extracellular (bath) solution contains (in mM): 2 CaCI2, 140 NaCI, 1 MgCI2, 10 HEPES, 4 KCI, 10 glucose, pH 7.3. D-(-)-2-amino- 5-phosphonopentanoic acid (D-AP5; 50 IM), 6-cyano-7-nitroquinoxaline-2, 3-dione (CNQX; 10 IM) and picrotoxin (PTX; 30 IM) are added to block synaptic transmission. T ransduced excitatory neurons are identified with EGFP fluorescence and from a pyramidal somatic shape. Neurons with unstable resting potential (or 4-50 mV), access resistance (Ra) 415 MX and/or holding current 4200 pA at -70 mV are discarded. Bridge balance compensation is applied and the resting membrane potential is held at -70 mV. A current step protocol is used to evoke action potentials by injecting 250-ms long depolarizing current steps of increasing amplitude from -20 pA (D10 pA). Recordings are acquired using a MultiClampTM 700A amplifier (Axon Instruments, Molecular Devices) and a Power3 1401 (CED) interface combined with Signal software (CED), filtered at 10 kHz and digitized at 50 kHz.

Electrophysiology (Ex vivo current clamp recordings): Current clamp recordings are performed in standard external solution in the presence of DL-AP5 (50 IM), CNQX (10 IM) and PTX (30 IM) to block NMDA, AMPA/kainate, and GABAA receptors, respectively. The internal solution is the same as for in vitro patch clamp recordings. Neurons with holding current 4100 pA and Ra 420 MX upon whole-cell breakin in voltage clamp mode and membrane potential less negative than -60 mV in current clamp are not considered for analysis. A 1440 DigidataVR (Molecular Devices) or Power3 1401 (CED) interface and MultiClampTM 700A (Molecular Devices) amplifier is used.

Electrophysiology (In vitro and ex vivo electrophysiology analysis): Electrophysiology analysis is performed with an automated Python script. Passive properties are calculated from the hyperpolarizing steps of the current clamp steps protocol. Input resistance is averaged from three current steps (two negative and one positive). Capacitance is calculated from the hyperpolarizing current step as follows. First, the input resistance is determined as the steady state DV/DI (voltage/current), then the cell time constant (tau) is obtained by fitting the voltage relaxation between the baseline and the hyperpolarizing plateau. Capacitance is then calculated as tau/resistance. Single action potential parameters are calculated as previously described (Pozzi et al., 2013). An event is detected as an action potential if it crossed 0 mV and if the rising slope was 420 mV/ms in a range of injected currents from 0 pA to 500 pA. The experiments are performed at room temperature (22-24°C). All recordings and analyses are carried out blind to vector transduced.

Electrophysiology (Activity clamp): The template simulating the barrage of synaptic conductances during epileptiform bursts is previously described (Morris et al., 2017). Dynamic clamp software (Signal 6.0, Cambridge Electronic Design, Cambridge, UK) and a Power3 1401 (CED) are used to inject both excitatory and inhibitory conductance templates simultaneously in a neuron recorded in current clamp configuration (iteration frequency 15 kHz). Erev is set to 0 mV and -75 mV for excitatory and inhibitory conductances, respectively, and corrected for a liquid junction potential of 14.9 mV. Incrementing synaptic conductances are injected in recorded neurons to establish the conductance threshold for action potential generation. Current clamp recordings for activity clamp are performed with the same external and internal solutions as given above. Surgical procedures: Surgical procedures are performed in anaesthetized adult mice (2-3 months) placed in a stereotaxic frame (Kopf).

Surgical procedures (Epilepsy model): Kainic acid (0.3 mg of 10 mg/ml, Tocris) is injected in a volume of 200 nl (7.14 mM effective concentration) in the right amygdala (antero-posterior: -0.94; medio-lateral: 2.85; dorsoventral: 3.75) at 200 nl/min under isoflurane anaesthesia (surgery time 10-15 min). The mice are allowed to recover from anaesthesia at 32°C for 5 min and then moved back to their cage where they are monitored closely during status epilepticus. Status epilepticus (characterized by stage 5 seizures on the Racine scale) usually begin 10-15 min after complete recovery and end 40 min after kainic acid injection with 10 mg/kg intraperitoneal diazepam. Only animals that exhibit at least one seizure per week are included in the subsequent study.

Surgical procedures (Stereotaxic viral injection): AAV9 viruses (300 nl, 1 :1 ratio) are injected with a 5-ml Hamilton syringe (33-Gauge) at 100 nl/min in three different coordinates of the right ventral hippocampus (Paxinos Mouse Brain Atlas; antero-posterior: -2/3 bregma/lambda distance; medio-lateral: -3; dorso-ventral: 3.5/3/2.5). The needle is kept in place for 10 min after each injection.

Surgical procedures (Transmitter implantation): An electrocorticogram (ECoG) transmitter (A3028C-CC Open Source Instruments, Inc.) is subcutaneously implanted and the recording electrode is placed in the cortex above the viral injection site (antero-posterior: -2/3 bregma/lamda distance; medio-lateral: -3). The ground electrode is placed in the contralateral frontal hemisphere.

Surgical procedures (Doxycycline diet): Animal food is changed to doxycycline ad libitum pellet (TD.120769-BLUE 625 mg/kg) after baseline recordings for the following 2 weeks.

Surgical procedures (Exclusion criteria): Animals recorded for the entire period of the experiment (6 weeks after kainic acid) are used in the analysis. At the end of the experiments some animal tissues are analysed with qRT-PCR and others were verified with immunofluorescence. Some mice injected with kainic acid are excluded because of infections or unexpected death in the first few days before planned implantation. To avoid possible bias, exclusions are made while researchers are blinded to treatment.

Surgical procedures (Pilocarpine acute seizure model): Male wild-type C57BLC/6J mice (3 months old) are anaesthetized with isoflurane and placed in a stereotaxic frame (David Kopf Instruments Ltd.). The animals are injected with 1.5 pl AAV CaMKII-CRISPR-Kcnal or CaMKII-CRISPR-LacZ at 100 nl/min in layer 2/3-5 primary visual cortex (coordinates: antero-posterior -2.8 mm, medio-lateral 2.4 from the bregma, and dorso-ventral 0.7/0.5/0.3 from pia). For ECoG monitoring, the recording electrode of 256 Hz single-channel ECoG transmitter (A3028C-CC, Open Source Instruments Inc.) is placed at the same coordinates. A reference electrode is placed in the contralateral skull. A cannula (Bilaney Consultants Ltd.) is implanted in the same location as the recording electrode for sequential pilocarpine injections. Animals are allowed to recover for 2 weeks before induction of acute seizures by pilocarpine (3.5 M in saline) (Magloire et al., 2019) injected 0.5 mm below the cannula using a microinjection pump (WPI Ltd.), a 5-ml Hamilton syringe (Esslab Ltd.), and a 33-Gauge needle (Esslab Ltd.). The injection volume is incremented on consecutive days (180 nl, 300 nl and 500 nl) until spike-wave discharges are observed, and recorded as the threshold dose. If seizures fail to terminate spontaneously, the animal is excluded from the study. To assess the treatment, the animals are placed on a doxycycline diet for 7 days and only the threshold dose for the animal is repeated. ECoG monitoring is used to assess seizure severity for an hour after the pilocarpine injection. The researcher who acquired and analysed the data is blinded to the virus injected. EEG (or ECoG) recordings: The ECoG is acquired wirelessly using hardware and software from Open Source Instruments, Inc. The ECoG is sampled at a frequency of 256 Hz, band-pass filtered between 1 and 160 Hz, and recorded continuously for the duration of the experiments. The animals are housed independently in a Faraday cage.

EEG analysis: Spontaneous seizures are detected from chronic recordings using a semi-automated supervised learning approach. First, a library containing examples of epileptiform activity is built using seizures identified from visual inspection of ECoG data. The recordings are saved in hour-long files, and for each seizure this full hour is included in the library. Recordings are chunked into 5-s blocks that are labelled as either ‘ictal’ or 'I nterictal ’ if they contained epileptiform-labelled activity or not, respectively. For each 5-s chunk of recording, 15 features are extracted. A random forest discriminative classifier is trained on the features and labels of each of the 5-s examples in the library (Breiman, 2001). In addition, cross-validation generated classifier predictions are used to parameterize a Hidden Markov Model in which the hidden states were the human annotations and the emissions the classifier predictions. For automated detection of epileptiform activity from unlabelled recordings, the discriminative classifier is first used to predict the class of consecutive 5-s chunks. The forward-backward algorithm is then applied to obtain the marginal probability of being in seizure state for each recording chunk given the surrounding classifier predictions. The smoothed predictions are then manually verified, false positives removed from the analysis and start and end locations adjusted. To quantify the performance this approach, four 2-week sets of recordings are randomly selected and visually examined for seizures and compared to classifier predictions (blinded).

Video recordings: IP cameras from Microseven (https://www.microseven.com/index.html) are used and synchronized via the Windows time server to the same machine as used to acquire the ECoG. Continuous video recordings produce six videos per hour.

Immunohistochemistry: Immunostaining is performed on 50-mm mouse brain PFAfixed sections with the following antibodies: mouse anti-GAD67 (MAB5406, Merck), rabbit anti-RFP (600-401-379, Rockland), Alexa FluorVR 555 goat anti-rabbit (A32732,lnvitrogen) and Alexa FluorVR 488 goat anti-mouse (A32723,

Invitrogen). Images are acquired with ZEN software (Zeiss) on a LSM710 confocal microscope (Zeiss) and co- localization analysis of tdTomato and GAD67 is performed with Imaged 1 .51 n (Wayne Rasband, National Institute of Health) plugin ‘JACoP’.

Behaviour tests: Trials started 2 weeks post-virus injection, are carried out between 7 am and 7 pm, during the light phase. Animals (3 months old) are habituated in the designated behaviour room for at least 15 min in home cages prior to the test.

Object Location Test: For the familiarization phase, mice are placed individually in the arena (50 cm > 50 cm _ 40 cm) and for 8 min, and allowed to explore two identical objects placed in the arena at least 5 cm away from the border. After a 6-h retention delay, the animals are returned to the same arena with one of the objects randomly relocated to a new location. The animal is allowed to explore for 8 min with video recordings. The arena and objects are thoroughly cleaned with ethanol between each session.

Novel Object Recognition Test: Twenty-four hours after the Object Location Test, the same animals are subjected to the Novel Object Recognition Test. The familiarization session is the same as for the Object Location Test. After a 6- h retention delay, one of the objects was randomly replaced by a novel object with a different shape and surface texture. The animals are allowed to explore freely for 8 min (Leger et al., 2013). All trials are recorded with a Raspberry Pi 3B + equipped with a V1 camera module (https://www.raspberrypi.org/documentation/hardware/camera/) and using Raspivid version 1.3.12 as 1296 _ 972 pixel, 30 frame/s MP4 video files. Automated analysis is carried out with custom scripts written in Bonsai version 2.4- preview (Lopes et al., 2015). A researcher is blinded to the treatment assessed and scores the exploration time manually after automated analysis. Discrimination index (DI) is calculated using the following formula: (time spent with altered object- time spent with unchanged object) I (total time spent exploring objects).

Statistical analysis: Data are plotted as box and whiskers, representing interquartile range (box), median (horizontal line), and maximum and minimum (whiskers), together with all the points. The mean is further shown as a plus symbol. The statistical analysis performed is shown in each figure legend. Deviation from normal distributions was assessed using D’Agostino-Pearson’s test, and the Ftest is was used to compare variances between two sample groups. Student’s two-tailed t-test (parametric) or the Mann-Whitney test (non-parametric) are used as appropriate to compare means and medians. Fisher’s exact test is used to analyse the contingency table. To compare two groups at different time points two-way repeated measure ANOVA is used, followed by Bonferroni post hoc test for functional analysis. Statistical analysis is carried out using Prism (GraphPad Software, Inc., CA, USA) and SPSS (IBM SPSS statistics, NY, USA).

Data availability: The Python and Bonsai scripts are made freely available. Plasmids are deposited with Addgene, and transcriptomic data are deposited in the NCBI Gene Expression Omnibus repository.

Administration and dosaqe

The inventive products described herein can be delivered to the subject in a variety of ways disclosed below, such as direct injection into the brain. For example, the treatment may involve direct injection of the viral particles into the cerebral cortex, in particular the neocortex or hippocampal formation. Another site of injection is an area of cortical malformation or hamartoma suspected of generating seizures, as occurs in focal cortical dysplasia or tuberous sclerosis. The treatment may involve direct injection of the viral particles into the location in the brain where it is believed to be functionally associated with the disorder. For example, where the treatment is for myoclonic epilepsy this may involve direct injection of the viral particles into the motor cortex; where the treatment is for chronic or episodic pain, this may involve direct injection of the viral particles into the dorsal root ganglia, trigeminal ganglia or sphenopalatine ganglia; and where the treatment is for Parkinson’s disease, this may involve direct injection of the viral particles into the substantia nigra, subthalamic nucleus, globus pallidus or putamen. The particular method and site of administration would be at the discretion of the physician who would also select administration techniques using his/her common general knowledge and those techniques known to a skilled practitioner.

In some embodiments, the therapy can be delivered via a direct injection into the hippocampal region and in the first instance can be trialled by on patients that are scheduled to undergo surgery thereby reducing the risk of this approach.

The invention may also be used to treat multiple epileptic foci simultaneously by injection directly into the multiple identified loci.

The treated neural cell may be a neuron or a glial cell. In particularly preferred embodiments, the neural cell is a neuron. In some embodiments, the neuron is a cortical neuron.

The patient may be one who has been diagnosed as having drug-resistant or medically-refractory epilepsy, by which is meant that epileptic seizures continue despite adequate administration of antiepileptic drugs. The subject may be one who has been diagnosed as having well defined focal epilepsy affecting a single area of the neocortex of the brain. Focal epilepsy can arise, for example, from developmental abnormalities or following strokes, tumours, penetrating brain injuries or infections.

Following administration of the viral particles, the recipient individual may exhibit reduction in symptoms of the disease or disorder being treated. For example, for an individual being treated who has a seizure disorder such as epilepsy, the recipient individual may exhibit a reduction in the frequency or severity of seizures. This may have a beneficial effect on the disease condition in the individual.

The term “treatment,” as used herein in the context of treating a condition, pertains generally to treatment and therapy of a human, in which some desired therapeutic effect is achieved, for example, the inhibition of the progress of the condition, and includes a reduction in the rate of progress, a halt in the rate of progress, regression of the condition, amelioration of the condition, and cure of the condition. Treatment as a prophylactic measure (i.e., prophylaxis, prevention) is also included.

The viral particles, vectors and other products disclosed herein can be delivered in a therapeutically-effective amount.

The term “therapeutically-effective amount” as used herein, pertains to that amount of the viral particles which is effective for producing some desired therapeutic effect, commensurate with a reasonable benefit/risk ratio, when administered in accordance with a desired treatment regimen.

Similarly, the term “prophylactically effective amount,” as used herein pertains to that amount of the viral particle which is effective for producing some desired prophylactic effect, commensurate with a reasonable benefit/risk ratio, when administered in accordance with a desired treatment regimen.

“Prophylaxis” in the context of the present specification should not be understood to describe complete success i.e. complete protection or complete prevention. Rather prophylaxis in the present context refers to a measure which is administered in advance of detection of a symptomatic condition with the aim of preserving health by helping to delay, mitigate or avoid that particular condition.

While it is possible for the vectors to be used (e g., administered) alone, it is often preferable to present it as a composition or formulation e.g. with a pharmaceutically acceptable carrier or diluent.

The term “pharmaceutically acceptable,” as used herein, pertains to compounds, ingredients, materials, compositions, dosage forms, etc., which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of the subject in question (e.g., human) without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit/risk ratio. Each carrier, diluent, excipient, etc. must also be “acceptable” in the sense of being compatible with the other ingredients of the formulation.

In some embodiments, the composition is a pharmaceutical composition (e.g., formulation, preparation, medicament) comprising, or consisting essentially of, or consisting of as a sole active ingredient, viral particle as described herein, and a pharmaceutically acceptable carrier, diluent, or excipient.

As described in W02008096268, in gene therapy embodiments employing delivery of the viral particle, the unit dose may be calculated in terms of the dose of viral particles being administered. Viral doses include a particular number of virus particles or plaque forming units (pfu). For embodiments involving adenovirus, particular unit doses include 10 ³ , 10 ⁴ , 10 ⁵ , 10 ⁶ , 10 ⁷ , 10 ⁸ , 10 ⁹ , 10 ¹⁰ , 10 ¹¹ , 10 ¹² , 10 ¹³ or 10 ¹⁴ pfu. Particle doses may be somewhat higher (10 to 100 fold) due to the presence of infection-defective particles.

In some embodiments the methods or treatments of the present invention may be combined with other therapies, whether symptomatic or disease modifying.

The term “treatment” includes combination treatments and therapies, in which two or more treatments or therapies are combined, for example, sequentially or simultaneously.

For example it may be beneficial to combine treatment with a compound as described herein with one or more other (e.g. , 1 , 2, 3, 4) agents or therapies.

Appropriate examples of co-therapeutics will be known to those skilled in the art on the basis of the disclosure herein. Typically the co-therapeutic may be any known in the art which it is believed may give therapeutic effect in treating the diseases described herein, subject to the diagnosis of the individual being treated. For example epilepsy can sometimes be ameliorated by directly treating the underlying etiology, but anticonvulsant drugs, such as phenytoin, gabapentin, lamotrigine, levetiracetam, carbamazepine, clobazam, topiramate, and others, which suppress the abnormal electrical discharges and seizures, are the mainstay of conventional treatment (Rho & Sankar, 1999, Epilepsia 40: 1471-1483).

The particular combination would be at the discretion of the physician who would also select dosages using his/her common general knowledge and dosing regimens known to a skilled practitioner.

The agents (i.e. viral particle, plus one or more other agents) may be administered simultaneously or sequentially, and may be administered in individually varying dose schedules and via different routes. For example, when administered sequentially, the agents can be administered at closely spaced intervals (e.g., over a period of 5-10 minutes) or at longer intervals (e.g., 1 , 2, 3, 4 or more hours apart, or even longer periods apart where required), the precise dosage regimen being commensurate with the properties of the therapeutic agent(s).

Cells

The invention also provides a cell comprising the vectors described herein. In some embodiments, this cell is a mammalian cell such as a human cell. In some embodiments, the cell is a human embryonic kidney cell (HEK) 293. In some embodiments, the cell is derived from a neuroblastoma cell-line.

Kits

The invention also provides kits that comprise an expression vector or expression vector system as described herein and one or more viral packaging and envelope expression vectors also described herein. In some embodiments the viral packaging expression vector is an integrase-deficient viral packaging expression vector.

Methods of determining expression of genes

The invention also provides methods of determining the expression of a first and/or second endogenous human gene as disclosed herein. One such method comprises:

(i) transducing a cell with an expression vector or expression vector system of any one of the above claims or administering a viral particle of any one of the above claims to a cell under conditions that permit expression of the first human gene and/or second gene; (ii) measuring the amount of the expression product of the first human gene and/or second gene, and comparing it to the amount of the expression product of the first human gene and/or second gene in a cell not transduced with expression vector, expression vector system or viral particle.

Measurement of expression could be determined by hybridisation assay or any other technique known in the art. This method can be carried out in vitro or ex vivo, for example in cell culture or in cells explanted from a human or animal body. Alternatively, the method can be carried out in vivo, for example where the viral particles are administered to a cell in a human or animal subject before extracting the cells or tissues from the human or animal subject in order to detect the expression of the genes.

Hybridisation assays are known in the art and generally involve using complementary nucleic acid probes (such as in situ hybridization using labelled probe, Northern blot and related techniques). In some embodiments, the hybridisation assay is an in situ hybridisation assay using a labelled probe, such as a fluorescently labelled probe.

As used herein, the term "probe" refers to a nucleic acid used to detect a complementary nucleic acid. Typically the probe is an RNA probe.

Suitable selective hybridisation conditions for oligonucleotides of 17 to 30 bases include hybridization overnight at 42°C in 6X SSC and washing in 6X SSC at a series of increasing temperatures from 42 °C to 65 °C. One common formula for calculating the stringency conditions required to achieve hybridization between nucleic acid molecules of a specified sequence homology is (Sambrook et al., 1989): Tm = 81.5 °C + 16.6Log [Na+] + 0.41 (% G+C) - 0.63 (% formamide) - 600/#bp in duplex.

***

Any sub-titles herein are included for convenience only, and are not to be construed as limiting the disclosure in any way. The invention will now be further described with reference to the following non-limiting Figures and Examples. Other embodiments of the invention will occur to those skilled in the art in the light of these. The disclosure of all references cited herein, inasmuch as it may be used by those skilled in the art to carry out the invention, is hereby specifically incorporated herein by cross-reference.

Figures

Figure 1 : GABRA5 CRISPRa in vitro screening. A. Schematic representation of the CRISPRa components: expression vectors containing (1) the different GABRA5 sgRNAs to be tested or control sgRNA targeting LacZ; (2) enzymatically inactivated Cas9 fused with transcription activators VP64 and a schematic representation of the RNA:Protein complex of the CRISPRa system. B. Schematic representation of the workflow to test the sgRNAs’ efficiency by co-transfection of both plasmids into the mouse cell line N2A followed by total mRNA RT-qPCR comparative analysis. C. Normalized GABRA5 mRNA expression relative to LacZ control by three sgRNAs (n=8, ***p=0.0005, One-Way ANOVA with Bonferroni’s post hoc test).

Figure 2: qPCR data for Kcnq2, Kcnq3, Lgi1, Kcna2, Gabral, Gabra2, Npy CRISPRa in vitro screening. A. Normalized Kcnq2 mRNA expression relative to LacZ control by 5 sgRNAs (n=3/4, *p<0.05; **p<0.01 ;***p<0.001 , One-Way ANOVA with Bonferroni’s post hoc test). B. Normalized Kcnq3 mRNA expression relative to LacZ control by three sgRNAs (n=1). C. Normalized Lgi1 mRNA expression relative to LacZ control by three sgRNAs (n=3/4, One- Way ANOVA with Bonferroni’s post hoc test). D. Normalized Kcna2 mRNA expression relative to LacZ control by three sgRNAs (n=4, **p<0.01 , One-Way ANOVA with Bonferroni’s post hoc test). E. Normalized Gabral mRNA expression relative to LacZ control by three sgRNAs (n=3, One-Way ANOVA with Bonferroni’s post hoc test). F. Normalized Gabra2 mRNA expression relative to LacZ control by three sgRNAs (n=1). G. Normalized Npy mRNA expression relative to LacZ control by three sgRNAs (n=4, ** p<0.01, One-Way ANOVA with Bonferroni’s post hoc test).

Figure 3: Design of AAV9 constructs for MEA using dual sgRNAs and sadCAS9 driven by a human CAMK2A (also known as CaMKII) promoter specific for excitatory neurons.

Figure 4: In vivo combinatorial KCNA1 and GABRA5 CRISPRa. A. Schematic representation of the CRISPRa components: AAV9 vectors containing (1) sgRNA:/<CA/A7-19 and sgRNA:GASRA5-3 or control sgRNA targeting LacZ; (2) enzymatically inactivated Cas9 fused with transcription activators VP64 and a schematic representation of the RNA:Protein complex of the multiplexing CRISPRa system. B. Schematic representation of the tri-transfection method of AAV production, where HEK-293T cells are transfected with a transgene, a capsid and a helper plasmid. AAV virions can then be collected from the culture media and cell lysate. C. Schematic representation of the stereotaxic apparatus used for precise location intra-cerebral injections and schematic of the subcutaneous placement of the wireless ECoG transmitter battery and position of electrodes through burr holes. D. Timeline of intra-amygdala model and gene therapy protocol.

Figure 5: In vivo combinatorial KCNA1 and GABRA5 CRISPRa. CRISPRa for Kenai alone (Kcna1-dCAS9A) was compared to the combination of Kenai and Gabra5 (Kcna1-Gabra5-dCAS9A). A. Number of seizures per day normalised to baseline. Left bar per each day refers to Kcna1-dCAS9A; Right bar per each day refers to Kcnal- Gabra5-dCAS9A. Greybox: after treatment. B. Percentage of seizures after treatment compared to baseline recording. C. Number of days seizure free in baseline compared to after the CRISPRa treatment. P=0.006 2-way ANOVA followed by Bonferroni multiple comparison test.

Figure 6: MEA Kcnq2-Kcnq3 combination. MEA recordings were performed at 14 DIV, 7 days after AAV9 transduction with either control (lacz+sadCAS9), single sgRNAs+sadCAS9, or combined sgRNAs+sadCAS9. Different parameters were extracted such as Spike frequency, Burst Frequency, Network Burst frequency, Burst Duration, and Inter-burst Interval. Only the most relevant are shown here. *p<0.05; **p<0.01; ***p<0.001 One-Way ANOVA vs CTRL (LacZ) with Bonferroni’s post hoc test.

Figure 7: MEA Kcna2-Lgi1 combination. MEA recordings were performed at 14 DIV, 7 days after AAV9 transduction with either control (lacz+sadCAS9), single sgRNAs+sadCAS9, or combined sgRNAs+sadCAS9. Different parameters were extracted such as Spike Frequency, Burst Frequency, Network Burst Frequency, Burst Duration, and Inter-burst Interval. Only the most relevant are shown here. *p<0.05; **p<0.01 ; ***p<0.001 ; ****p<0.0001 , One-Way ANOVA vs CTRL (LacZ) with Bonferroni’s post hoc test.

Figure 8: MEA Kcnq3-Lgi1 combination. MEA recordings were performed at 14 DIV, 7 days after AAV9 transduction with either control (lacz+sadCAS9), single sgRNAs+sadCAS9, or combined sgRNAs+sadCAS9. Different parameters were extracted such as Spike Frequency, Burst Frequency, Network Burst Frequency, Burst Duration, and Inter-burst Interval. Only the most relevant are shown here. *p<0.05 One-Way ANOVA vs CTRL (LacZ) with Bonferroni’s post hoc test.

Figure 9: Design AAV9 constructs for DRG recordings using dual sgRNAs and sadCAS9 driven by a CMV promoter. Figure 10: DRG patch clamp - Kcnq2-Kcnq3 combination. Current clamp recordings were performed at 5 DIV after dissociation and AAV9 transduction with either control (lacz+sadCAS9), single sgRNAs+sadCAS9 or combined sgRNAs+sadCAS9. Different parameters were extracted such as Number of Action Potentials, Maximal Firing Rate, and Current Threshold. Only the most relevant are shown here. *p<0.05; two-way ANOVA; *p<0.05, **p<0.01 ; One- Way ANOVA vs CTRL (LacZ) with Bonferroni’s post hoc test.

Figure 11 : DRG patch clamp - Kcna2-Kcnj2 combination. Current clamp recordings were performed at 5 DIV after dissociation and AAV9 transduction with control (lacz+sadCAS9) or combined sgRNAs+sadCAS9. Different parameters were extracted such as Number of Action Potentials, Maximal Firing Rate, and Current Threshold. Only the most relevant are shown here. **p<0.01 ; two-way ANOVA; *p<0.05, Unpaired Student’s t test.

Figure 12: Schematic of a particularly preferred CRISPRa embodiment of the invention.

Figure 13: Bioinformatic analysis of the human KCNA1 promoter, and sgRNA design in the 600bp promoter region before the TSS for human KCNA1. Analysis of the promoter region for sgRNA using sadCas9 is also shown at bottom.

Figure 14: RNAseq data from human KCNA1 experiments. A. Gene expression alterations in epilepsy and rescue after gene therapy with dCas9A driven expression of KCNA1 (NE=non epileptic; E= epileptic). B. Gene expression alterations in epilepsy for selected genes, known to be protective for epilepsy.

Figure 15: Promoter Analysis for human GABRA5

Figure 16: sgRNA design in the 600bp promoter region before the TSS for human GABRA5. Analysis of the promoter region for sgRNA using sadCas9 is also shown at bottom.

Figure 17: Promoter Analysis for human KCNA2

Figure 18: sgRNA design in the 600bp promoter region before the TSS for human KCNA2. Analysis of the promoter region for sgRNA using sadCas9 is also shown at bottom.

Figure 19: Promoter Analysis for human LGI1

Figure 20: sgRNA design in the 600bp promoter region before the TSS for human LGI1. Analysis of the promoter region for sgRNA using sadCas9 is also shown at bottom.

Figure 21 : Promoter Analysis for human KCNC1

Figure 22: sgRNA design in the 600bp promoter region before the TSS for human KCNC1. Analysis of the promoter region for sgRNA using sadCas9 is also shown at bottom.

Figure 23: Promoter Analysis for human KCNMA1

Figure 24: sgRNA design in the 600bp promoter region before the TSS for human KCNMA1. Analysis of the promoter region for sgRNA using sadCas9 is also shown at bottom.

Figure 25: Promoter Analysis for human KCNK2 Figure 26: sgRNA design in the 600bp promoter region before the TSS for human KCNK2. Analysis of the promoter region for sgRNA using sadCas9 is also shown at bottom.

Figure 27: Promoter Analysis for human KCNQ2

Figure 28: sgRNA design in the 600bp promoter region before the TSS for human KCNQ2. Analysis of the promoter region for sgRNA using sadCas9 is also shown at bottom.

Figure 29: Promoter Analysis for human KCNQ3

Figure 30: sgRNA design in the 600bp promoter region before the TSS for human KCNQ3. Analysis of the promoter region for sgRNA using sadCas9 is also shown at bottom.

Figure 31 : Promoter Analysis for human KCNJ6

Figure 32: sgRNA design in the 600bp promoter region before the TSS for human KCNJ6. Analysis of the promoter region for sgRNA using sadCas9 is also shown at bottom.

Figure 33: Promoter Analysis for human GRM2

Figure 34: sgRNA design in the 600bp promoter region before the TSS for human GRM2. Analysis of the promoter region for sgRNA using sadCas9 is also shown at bottom.

Figure 35: Promoter Analysis for human GDNF

Figure 36: sgRNA design in the 600bp promoter region before the TSS for human GDNF. Analysis of the promoter region for sgRNA using sadCas9 is also shown at bottom.

Figure 37: Promoter Analysis for human NPY

Figure 38: sgRNA design in the 600bp promoter region before the TSS for human NPY. Analysis of the promoter region for sgRNA using sadCas9 is also shown at bottom.

Figure 39: Promoter Analysis for human NPY2R

Figure 40: sgRNA design in the 600bp promoter region before the TSS for human NPY2R. Analysis of the promoter region for sgRNA using sadCas9 is also shown at bottom.

Figure 41 : Promoter Analysis for human GALP

Figure 42: sgRNA design in the 600bp promoter region before the TSS for human GALP. Analysis of the promoter region for sgRNA using sadCas9 is also shown at bottom.

Figure 43: Promoter Analysis for human GALR1

Figure 44: sgRNA design in the 600bp promoter region before the TSS for human GALR1. Analysis of the promoter region for sgRNA using sadCas9 is also shown at bottom. Figure 45: Promoter Analysis for human PDYN

Figure 46: sgRNA design in the 600bp promoter region before the TSS for human PDYN. Analysis of the promoter region for sgRNA using sadCas9 is also shown at bottom.

Figure 47: Promoter Analysis for human BDNF

Figure 48: sgRNA design in the 600bp promoter region before the TSS for human BDNF. Analysis of the promoter region for sgRNA using sadCas9 is also shown at bottom.

Figure 49: Promoter Analysis for human FGF2

Figure 50: sgRNA design in the 600bp promoter region before the TSS for human FGF2. Analysis of the promoter region for sgRNA using sadCas9 is also shown at bottom.

Figure 51 : Promoter Analysis for human GABBR1

Figure 52: sgRNA design in the 600bp promoter region before the TSS for human GABBR1. Analysis of the promoter region for sgRNA using sadCas9 is also shown at bottom.

Figure 53: Promoter Analysis for human GABBR2

Figure 54: sgRNA design in the 600bp promoter region before the TSS for human GABBR2. Analysis of the promoter region for sgRNA using sadCas9 is also shown at bottom.

Figure 55: Promoter Analysis for human GRM3

Figure 56: sgRNA design in the 600bp promoter region before the TSS for human GRM3. Analysis of the promoter region for sgRNA using sadCas9 is also shown at bottom.

Figure 57: Promoter Analysis for human GRM4

Figure 58: sgRNA design in the 600bp promoter region before the TSS for human GRM4. Analysis of the promoter region for sgRNA using sadCas9 is also shown at bottom.

Figure 59: Promoter Analysis for human GRM7

Figure 60: sgRNA design in the 600bp promoter region before the TSS for human GRM7. Analysis of the promoter region for sgRNA using sadCas9 is also shown at bottom.

Figure 61 : Promoter Analysis for human GABRR1

Figure 62: sgRNA design in the 600bp promoter region before the TSS for human GABRR1. Analysis of the promoter region for sgRNA using sadCas9 is also shown at bottom.

Figure 63: Promoter Analysis for human GABRR3 Figure 64: sgRNA design in the 600bp promoter region before the TSS for human GABRR3. Analysis of the promoter region for sgRNA using sadCas9 is also shown at bottom.

Figure 65: Promoter Analysis for human OPRK1

Figure 66: sgRNA design in the 600bp promoter region before the TSS for human OPRK1. Analysis of the promoter region for sgRNA using sadCas9 is also shown at bottom.

Figure 67: Promoter Analysis for human OPRM1

Figure 68: sgRNA design in the 600bp promoter region before the TSS for human OPRM1. Analysis of the promoter region for sgRNA using sadCas9 is also shown at bottom.

Figure 69: Promoter Analysis for human OPRD1

Figure 70: sgRNA design in the 600bp promoter region before the TSS for human OPRD1. Analysis of the promoter region for sgRNA using sadCas9 is also shown at bottom.

Figure 71 : Promoter Analysis for human OPRL1

Figure 72: sgRNA design in the 600bp promoter region before the TSS for human OPRL1. Analysis of the promoter region for sgRNA using sadCas9 is also shown at bottom.

Figure 73: Promoter Analysis for human KCNJ2

Figure 74: sgRNA design in the 600bp promoter region before the TSS for human KCNJ2. Analysis of the promoter region for sgRNA using sadCas9 is also shown at bottom.

Figure 75: Promoter Analysis for human GABRA1

Figure 76: sgRNA design in the 600bp promoter region before the TSS for human GABRA1. Analysis of the promoter region for sgRNA using sadCas9 is also shown at bottom.

Figure 77: Promoter Analysis for human GABRA2

Figure 78: sgRNA design in the 600bp promoter region before the TSS for human GABRA2. Analysis of the promoter region for sgRNA using sadCas9 is also shown at bottom.

Examples

Example 1 - sgRNA validation for Gabra5 and testing in vitro

5 sgRNAs were made that were scored as top potential sequences in the proximal promoter of Gabra5 to increase its expression with CRISPRa. Furthermore, at least 3 sgRNAs were made that were scored as top potential sequences in the proximal promoter of Kcnq2, Kcnq3, Lgi1, Kcnj2, Gabral, Gabra2, Npy and Kcna2 to increase their expression with CRISPRa.

They were co-transfected with sp or sadCas9-VP64 and total mRNA was analysed by RT-qPCR (Figure 1 B) by the procedure of described in Colasante 2020 and disclosed herein. Their ability to upregulate gene expression was validated using qPCR in N2A murine cells as previously described in Colasante 2020 (Figure 1 B, showing a schematic representation of the workflow to test the sgRNAs efficiency by co-transfection of both plasmids into the mouse cell line N2A followed by total mRNA RT-qPCR comparative analysis).

Figure 1A shows a schematic representation of the CRISPRa components: expression vectors containing (1) the different Gabra5 sgRNAs to be tested or control sgRNA targeting LacZ; (2) enzymatically inactivated Cas9 fused with transcription activators VP64 and a schematic representation of the RNA:Protein complex of the CRISPRa system.

Figure 1C (spdCas9) shows normalized Gabra5 mRNA expression relative to LacZ control by three sgRNAs (n=8, ***p=0.0005, One-Way ANOVA with Bonferroni’s post hoc test). sgRNA3 was capable of significantly upregulating GABRA5 expression when transfected into the murine N2A cell line.

Figure 2A (sadCAS9) shows normalized Kcnq2 mRNA expression relative to LacZ control by five sgRNAs (n=3/4, *p<0.05; **p<0.01 ;***p<0.001 , One-Way ANOVA with Bonferroni’s post hoc test). sgRNA5 was capable of significantly upregulating Kcnq2 expression when transfected into the murine N2A cell line.

Figure 2B (sadCAS9) shows normalized Kcnq3 mRNA expression relative to LacZ control by three sgRNAs (n=1). sgRNA3 was capable of upregulating Kcnq3 expression when transfected into the murine N2A cell line.

Figure 2C (sadCAS9) shows normalized Lgi1 mRNA expression relative to LacZ control by three sgRNAs (n=3/4, One-Way ANOVA with Bonferroni’s post hoc test). sgRNA2 was capable of consistently upregulating Lgi1 expression when transfected into the murine N2A cell line.

Figure 2D (sadCAS9) shows normalized Kcna2 mRNA expression relative to LacZ control by three sgRNAs (n=4, **p<0.01 , One-Way ANOVA with Bonferroni’s post hoc test). sgRNA2 was capable of significantly upregulating Kcna2 expression when transfected into the murine N2A cell line.

Figure 2E (sadCAS9) shows normalized Gabral mRNA expression relative to LacZ control by three sgRNAs (n=3, One-Way ANOVA with Bonferroni’s post hoc test). sgRNAI was capable of upregulating Gabral expression when transfected into the murine N2A cell line.

Figure 2F (sadCAS9) shows normalized Gabra2 mRNA expression relative to LacZ control by three sgRNAs (n=1 , One-Way ANOVA with Bonferroni’s post hoc test). sgRNAI was capable of upregulating Gabra2 expression when transfected into the murine N2A cell line.

Figure 2G (sadCAS9) shows normalized Npy mRNA expression relative to LacZ control by three sgRNAs (n=4, ** p<0.01 , One-Way ANOVA with Bonferroni’s post hoc test). sgRNA2 was capable of significantly upregulating Npy expression when transfected into the murine N2A cell line.

Example 2 - Determination of target genes for combinatorial gene therapy

Although a previous study (Colasante 2020) provided the proof of principle for a translational CRISPR-based approach to treat neurological diseases, only a 50% decrease in seizures was observed. A similar degree of efficacy has been observed with other gene therapy approaches for epilepsy.

Furthermore, although CRISPRa targeting Kenai led to a degree of rescue at the level of transcriptomics some altered gene expression was not fully corrected. Among these genes Gabra5, encoding the alpha5 subunit of GABAA receptors that contribute to tonic inhibition, was found to be downregulated in epileptic animals both before and after the therapy (Figure 14). Importantly, loss of function GABRA5 mutations have been associated with severe epileptic encephalopathies.

A combination therapy targeting endogenous KCNA1 and GABRA5 genes thus may lead to improved treatment of neurological diseases and disorders.

Moreover, the combinatorial activation of genes known to influence neuronal firing may lead to improved treatments for neurological diseases and disorders. Among these combinations KCNQ2 and KCNQ3, LGI1 and KCNA1 are promising for epilepsy; KCNA1 and KCNJ2, KCNQ2 and KCNQ3 are promising for pain.

Example 3 - AAV9 production, test in vitro and injection in vivo for combinatorial gene therapy

High-titer AAV9 have been produced. Either Kcna1/Gabra5-dC/\S9/\ or Kcna1-dCAS9A (using the spdCas9) were transduced in primary hippocampal neurons and then tested for efficacy using qPCR and multielectrode arrays(MEAs)/ or patch clamp electrophysiology at 14DIV after infection. The Gabra5 sgRNA used was sgRNA3 from Example 1 . The Kenai sgRNA is disclosed in the sequence annex.

Furthermore either Kcnq2-sadCAS9 or Kcnq3-sadCAS9 or Kcnq2/Kcnq3-sadCAS9, or Kcna2-sadCAS9 or Lgi1- sadCAS9 or Kcna2/Lgi1 -sadCasd, or Kcnq3-sadCAS9 or Lgi1-sadCAS9 or Kcnq3/Lgi1 -sadCasd (using the sadCAS9 - Figure 3) were transduced in primary hippocampal neurons and then tested for efficacy using multielectrode arrays (MEAs) at 14DIV after infection.

Status epilepticus (SE) was induced in mice by injecting kainic acid (KA) into the amygdala as previously described (Colasante, Qiu et al 2020) and treatment was then assessed. Kcna1/Gabra5-dCAS9A vs Kcna1 -dCAS9A was injected 2 weeks after SE and the CRISPRa tool was activated 2 weeks after an EEG baseline recording. Wireless EEG transmitters (Open Source Instruments) were implanted at 2 weeks post SE in parallel with the viral injection (2 AAVs controlled by doxycycline as previous described).

CRISPRa activation was achieved changing the normal diet to doxycycline supplement food. 3 weeks of EEG recordings after CRISPRa activation was performed. The animals were randomized and the researcher blinded to AAV. The mice were monitored with EEG-video telemetry for 5 weeks.

Behavioral features will be assessed in epileptic animals before and after the treatment such as novel object location, open field, T-Maze and a control test not related to hippocampal function (olfactory discrimination). Naive animals injected either withKcna1 /Gabra5-dCAS9A or Kcna1-dCAS9A will be used at the same time points to assess changes in basal behavioral tasks.

All AAV transfer plasmids for viral production (Figure 4A) have already been produced and viruses have been produced in-house (Figure 4B). Animals have been already injected with KA to induce the epilepsy model, already established in the lab, and transmitters will be implanted (Figure 4C and Figure 4D). The virus was then be injected as a potential gene therapy, where video-ECoG were used to assess its efficacy (Figure 4D).

An improvement in reduction of number of seizures was observed when animals were injected with Kcna1/Gabra5- dCAS9A compared toKcna1 -dCAS9A (Figure 5A and Figure 5B). Importantly, after CRISPRa activation animals injected withKcna1 /Gabra5-dCAS9A showed a net increase in days seizures free compared to animals injected with Kcna7-dCAS9A (Figure 5C). This result shows that combinatorial Kenai and Gabra5 CRISPRa therapy is more efficient in rescuing the epileptic phenotype compared to the single Kenai CRISPRa treatment.

Figure 6, Figure 7 and Figure 8 show a significant decrease in network excitability with the combinatorial approaches compared to control and single sgRNAs. This is associated with a greater antiepileptic effect as previously described (Qiu et al. 2022 Science).

Example 4 - further sgRNA design

Encyclopedia of DNA Elements (ENCODE) and the Functional ANnoTation Of the Mammalian genome (FANTOM) (Carninci et al., 2006) databases were used to download transcriptomics and epigenetics NGS data for each single human gene. Tracks were visualized along the human reference genome with the Integrative Genome Viewer (IGV) (Thorvaldsdottir et al., 2013). Relevant promoter sequences 600bp before the estimated Transcription Starting Site (TSS) were used to design the sgRNAs with CHOPCHOP (http://chopchop.cbu.uib.no/).

Based on this analysis, several lead candidates were generated for a variety of human gene promoter sequences.

Example 5 - AAV9 production, test in vitro in DRG neurons for combinatorial gene therapy

High-titer AAV9 have been produced. Either Kcnq2-sadCAS9 or Kcnq3-sadCAS9 or Kcnq2/Kcnq3-sadCAS9, or Kcna2-sadCAS9 or Kcnj2-sadCAS9 or Kcna2/kcnj2-sadCas9 (using the sadCAS9 - Figure 9) were transduced in dissociated DRG neurons and then tested for efficacy using patch clamp electrophysiology at 3-6DIV after infection.

Figure 10 and Figure 11 show a significant decrease in DRG excitability with both the combinatorial approaches compared to control and single sgRNAs. This can be associated with an in vivo therapeutic anti-pain effect (Krames E.S. 2015 Neuromodulation).

Example 6 - Selected Materials and Methods

Antibiotic screening in N2A or P19 cells lines: N2A cells were transfected with pAAV-plasmids that may contain sgRNA sequence, sadCas9 and antibiotic blasticidine resistance gene. The transfected N2A cells were selected for with 20mg/ml blasticidine for 48 hours in growth media. RNA extraction from N2A cells was carried out using RNAeasy Kit (Qiagen #74104) according to the manufacturer’s instruction. cDNA synthesis for quantitative RT-PCR (RT-qPCR) was acquired using the Superscript™ IV Reverse Transcriptase system. A Custom designed oligonucleotides was used to carry out RT-qPCR along with SYBR™ Green qPCR Mix. The relative expression was measured using the DDCT method, relative to the LacZ-sa_sgRNA condition.

AAV production was carried out using protocol adapted from Grieger et al, 2006. HEK 293T was previously maintained and passage weekly after reaching 80-90% confluency. The HEK 293T were then plates on 10 x 150 cm2 Petri Dishes (Thermo Scientific™ Nunc™ Cell Culture/Petri Dishes). Cells were then co-transfected following plating with helper, cap-rep and transfer plasmids at a molar ratio of 3: 1 :1 , PEI MAX transfection reagent (PEI MAX - Transfection Grade Linear Polyethylenimine Hydrochloride (MW 40,000)) was used at a ratio of 2 PEI : 1 DNA diluted in Opti-MEM (Opti-MEM I Reduced Serum Media). Typical harvest time was 96-120 hours after transfection. The viral particles were then purified using the iodixanol gradient method. The layer containing the viral particles was carefully extracted using an 18-gauge needle from the side of the tube. The AAV titers were then calculated using AAVpro® Titration Kit (Takara). All the in-house AAV produced had as estimated titer of at least least 10 ¹³ vg/ml, sufficient for in vitro production. There are a total of 15 viruses produced from the in-house AAV production. Mouse embryonic neuronal primary cultures were prepared and seeded on Axion multi-well multi-electro array (CytoView-24 well, Axion Biosystems) plate at 30,000 - 50,000 cells/well density. The neurons were transduced with AAV9 viruses at multiplicity of infection (MOI) > 10^9 at DIV7-10. The recordings were taken at 37 degree, 5% CO2 concentration for 10 minutes at 13 and 15DIV. The analysis were performed with AXIS Navigator (Axion Biosystems). The wells with no less than 50% active electrodes were considered viable data. The minimum vitality covered resistance is 18kΩ. The spikes were defined with more than 6xSTD above the baseline. The bursts were defined with Inter-burst interval (ISIS) threshold algorithm, maximum inter-spike interval of 100ms and minimum 5 spikes/burst. The minimum participating electrodes in a network burst is 35%.

Electrophysiology (in vitro, DRG neurons): dorsal ganglion neurons were dissected out and seeded at 1000 cells per coverslip (13mm) and cultured for 7 days. The neurons were transduced with AAV9 at MOI>10 ^A 9 on 0DIV. For current-clamp recordings, the internal solution (pipette) contains (in mM) 140 KCI, 0.5 EGTA, 5 HEPES, 3 Mg-ATP, pH = 7.3. The extracellular solution (bath) contains (mM) 140 NaCI, 3 KCI, 1 MgCI, 1 CaCl2.2H20, 10 HEPES, pH=7.3. The appropriate sub-type of DRG neurons were identified with visual confirmation, the cells were held at RMP or -60mV, while injecting series of 1s, 20pA current steps from -20pA to 600pA. A ramp protocol from -20pA to 600pA in 1s was evoked after the current step protocol completion. Recordings are acquired using a Axon Axopatch 200B Microelectrode Amplifier, filtered at 10 kHz and digitized at 50 kHz via a Digidata 1550B (Axon Instruments) combined with Clampex 10.4.

Expression vectors may be generated in the following exemplary protocols:

Small guide RNAs are cloned into a AAV (adeno-associated virus) vector with a U6 promoter (hU6) and saCas9 compatible scaffold. A defective Cas9 fused to the VP64 activator domain is cloned into a plasmid with Blasticidine (BSD) resistance gene, under the control of a CMV promoter (CMV-sadCas9-VP64-BSD). The sadCas9-VP64 cassette was obtained from a gift plasmid (pJEP304) from the Ploski lab. And the BSD-resistance gene was extracted from lentiviral plasmid dsaCas9-VP64_Blast.

For neuronal expressions, the CMV promoter from pJEP304 was digested and replaced with a short human CaMKII (shCaMKII) promoter sequence first with Mlul and EcoRI to produce shCaMKII-sadCas9-VP64. The sgRNA cassette (hU6-sgRNA) was extracted from pAAV-hU6-sgRNA-CMV-sadCas9-VP64-BSD with Mlul digestion and cloned into shCaMKII-sadCas9-VP64.

The dual-sgRNA cassette (hU6-sgRNA1-hU6-sgRNA2) was synthesised by GeneArt. The dual-sgRNA cassette for neuronal expression was cloned into shCaMKII-sadCas9-VP64 with Mlul and EcoRI digestion and ligation.

For DRG neuronal expressions, the sgRNA cassette was digested with Mlul and cloned directly into pJEP304 under the control of CMV promoter. The dual-sgRNA cassette (hU6-sgRNA1-hU6-sgRNA2) was synthesised by GeneArt. The dual-sgRNA cassette was cloned into the pJEP304 with Mlul digestion.

List of selected references

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Colasante G et al, dCas9-Based Senia Gene Activation Restores Inhibitory Interneuron Excitability and Attenuates Seizures in Dravet Syndrome Mice. Mol Ther. 2020 Jan 8;28(1):235-253. doi: 10.1016/j.ymthe.2019.08.018. Epub 2019 Sep 3. PMID: 31607539; PMCID: PMC6952031 Woldbye DPD et al, Adeno-associated viral vector-induced overexpression of neuropeptide Y Y2 receptors in the hippocampus suppresses seizures, Brain, Volume 133, Issue 9, September 2010, Pages 2778-2788, https://doi.orq/10.1093/brain/awq219

Wykes RC et al, Optogenetic and potassium channel gene therapy in a rodent model of focal neocortical epilepsy. Sci Transl Med. 2012 Nov 21 ;4(161 ): 161 ra152. doi: 10.1126/scitranslmed.3004190. Epub 2012 Nov 12. PMID: 23147003; PMCID: PMC3605784

Konermann, S., Brigham, M., Trevino, A. et al. Genome-scale transcriptional activation by an engineered CRISPR- Cas9 complex. Nature 517, 583-588 (2015). https://doi.org/10.1038/nature14136

Dominguez AA, et al , Beyond editing: repurposing CRISPR-Cas9 for precision genome regulation and interrogation. Nat Rev Mol Cell Biol. 2016 Jan; 17(1 ):5-15. doi: 10.1038/nrm.2015.2. Epub 2015 Dec 16. PMID: 26670017; PMCID: PMC4922510.

Adli M. The CRISPR tool kit for genome editing and beyond. Nat Commun. 2018 May 15;9(1 ): 1911 . doi: 10.1038/S41467-018-04252-2. PMID: 29765029; PMCID: PMC5953931

Liao HK et al, In Vivo Target Gene Activation via CRISPR/Cas9-Mediated Trans-epigenetic Modulation. Cell. 2017 Dec 14; 171 (7): 1495-15O7.e15. doi: 10.1016/j.cell.2O17.10.025. Epub 2017 Dec 7. PMID: 29224783; PMCID: PMC5732045

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Sequence Annex

Nucleotide sequence of sgRNA for mouse GABRA5; sgRNA1 (SEQ ID NO: 1)

GAGCGAGCGCGAGTCCGCCG

Nucleotide sequence of sgRNA for mouse GABRA5; sgRNA2 (SEQ ID NO: 2)

GGTGACTAGCGATTATTCCA

Nucleotide sequence of synthetic quide RNA for mouse GABRA5-, synthetic quide RNA3 (SEQ ID NO: 3)

AACATGGTCTTTCCCGAAGC

Nucleotide sequence of sgRNA for mouse GABRA5; sgRNA Lac Z control (SEQ ID NO: 4)

TGCGAATACGCCCACGCGAT pAAV-TetON dCas9-VP64 used in in vivo experiments (SEQ ID NO: 5)

CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAGCCCGGGC GTCGGGCGACCTTTG

GTCGCCCGGCCTCAGTGAGCGAGCGAGCGCGCAGAGAGGGAGTGGCCAACTCCATCA CTAGGGGTTCCTGCG

GCCTCTAGACCAGTTTGGTTAGATCTCGAGTTTACCACTCCCTATCAGTGATAGAGA AAAGTGAAAGTCGAGTTT

ACCACTCCCTATCAGTGATAGAGAAAAGTGAAAGTCGAGTTTACCACTCCCTATCAG TGATAGAGAAAAGTGAAA

GTCGAGTTTACCACTCCCTATCAGTGATAGAGAAAAGTGAAAGTCGAGTTTACCACT CCCTATCAGTGATAGAGA

AAAGTGAAAGTCGAGTTTACCACTCCCTATCAGTGATAGAGAAAAGTGAAAGTCGAG TTTACCACTCCCTATCAG

TGATAGAGAAAAGTGAAAGTCGAGCTCGGTACCCGGGTCGAGTAGGCGTGTACGGTG GGAGGCCTATATAAGC

AGAGCTCGTTTAGTGAACCGTCAGATCGCACCGGTGTCGACTCTAGAGCCACCATGC CCAAGAAGAAGAGGAA

GGTGGGAAGGGGGATGGACAAGAAGTACTCCATTGGGCTCGCTATCGGCACAAACAG CGTCGGCTGGGCCGT CATTACGGACGAGTACAAGGTGCCGAGCAAAAAATTCAAAGTTCTGGGCAATACCGATCG CCACAGCATAAAGA

AGAACCTCATTGGCGCCCTCCTGTTCGACTCCGGGGAGACGGCCGAAGCCACGCGGC TCAAAAGAACAGCACG

GCGCAGATATACCCGCAGAAAGAATCGGATCTGCTACCTGCAGGAGATCTTTAGTAA TGAGATGGCTAAGGTGG

ATGACTCTTTCTTCCATAGGCTGGAGGAGTCCTTTTTGGTGGAGGAGGATAAAAAGC ACGAGCGCCACCCAATC

TTTGGCAATATCGTGGACGAGGTGGCGTACCATGAAAAGTACCCAACCATATATCAT CTGAGGAAGAAGCTTGTA

GACAGTACTGATAAGGCTGACTTGCGGTTGATCTATCTCGCGCTGGCGCATATGATC AAATTTCGGGGACACTT

CCTCATCGAGGGGGACCTGAACCCAGACAACAGCGATGTCGACAAACTCTTTATCCA ACTGGTTCAGACTTACA

ATCAGCTTTTCGAAGAGAACCCGATCAACGCATCCGGAGTTGACGCCAAAGCAATCC TGAGCGCTAGGCTGTCC

AAATCCCGGCGGCTCGAAAACCTCATCGCACAGCTCCCTGGGGAGAAGAAGAACGGC CTGTTTGGTAATCTTAT

CGCCCTGTCACTCGGGCTGACCCCCAACTTTAAATCTAACTTCGACCTGGCCGAAGA TGCCAAGCTTCAACTGA

GCAAAGACACCTACGATGATGATCTCGACAATCTGCTGGCCCAGATCGGCGACCAGT ACGCAGACCTTTTTTTG

GCGGCAAAGAACCTGTCAGACGCCATTCTGCTGAGTGATATTCTGCGAGTGAACACG GAGATCACCAAAGCTCC

GCTGAGCGCTAGTATGATCAAGCGCTATGATGAGCACCACCAAGACTTGACTTTGCT GAAGGCCCTTGTCAGAC

AGCAACTGCCTGAGAAGTACAAGGAAATTTTCTTCGATCAGTCTAAAAATGGCTACG CCGGATACATTGACGGCG

GAGCAAGCCAGGAGGAATTTTACAAATTTATTAAGCCCATCTTGGAAAAAATGGACG GCACCGAGGAGCTGCTG

GTAAAGCTTAACAGAGAAGATCTGTTGCGCAAACAGCGCACTTTCGACAATGGAAGC ATCCCCCACCAGATTCA

CCTGGGCGAACTGCACGCTATCCTCAGGCGGCAAGAGGATTTCTACCCCTTTTTGAA AGATAACAGGGAAAAGA

TTGAGAAAATCCTCACATTTCGGATACCCTACTATGTAGGCCCCCTCGCCCGGGGAA ATTCCAGATTCGCGTGG

ATGACTCGCAAATCAGAAGAGACCATCACTCCCTGGAACTTCGAGGAAGTCGTGGAT AAGGGGGCCTCTGCCCA

GTCCTTCATCGAAAGGATGACTAACTTTGATAAAAATCTGCCTAACGAAAAGGTGCT TCCTAAACACTCTCTGCTG

TACGAGTACTTCACAGTTTATAACGAGCTCACCAAGGTCAAATACGTCACAGAAGGG ATGAGAAAGCCAGCATTC

CTGTCTGGAGAGCAGAAGAAAGCTATCGTGGACCTCCTCTTCAAGACGAACCGGAAA GTTACCGTGAAACAGCT

CAAAGAAGACTATTTCAAAAAGATTGAATGTTTCGACTCTGTTGAAATCAGCGGAGT GGAGGATCGCTTCAACGC

ATCCCTGGGAACGTATCACGATCTCCTGAAAATCATTAAAGACAAGGACTTCCTGGA CAATGAGGAGAACGAGG

ACATTCTTGAGGACATTGTCCTCACCCTTACGTTGTTTGAAGATAGGGAGATGATTG AAGAACGCTTGAAAACTT

ACGCTCATCTCTTCGACGACAAAGTCATGAAACAGCTCAAGAGGCGCCGATATACAG GATGGGGGCGGCTGTC

AAGAAAACTGATCAATGGGATCCGAGACAAGCAGAGTGGAAAGACAATCCTGGATTT TCTTAAGTCCGATGGATT

TGCCAACCGGAACTTCATGCAGTTGATCCATGATGACTCTCTCACCTTTAAGGAGGA CATCCAGAAAGCACAAGT

TTCTGGCCAGGGGGACAGTCTTCACGAGCACATCGCTAATCTTGCAGGTAGCCCAGC TATCAAAAAGGGAATAC

TGCAGACCGTTAAGGTCGTGGATGAACTCGTCAAAGTAATGGGAAGGCATAAGCCCG AGAATATCGTTATCGAG

ATGGCCCGAGAGAACCAAACTACCCAGAAGGGACAGAAGAACAGTAGGGAAAGGATG AAGAGGATTGAAGAGG

GTATAAAAGAACTGGGGTCCCAAATCCTTAAGGAACACCCAGTTGAAAACACCCAGC TTCAGAATGAGAAGCTCT

ACCTGTACTACCTGCAGAACGGCAGGGACATGTACGTGGATCAGGAACTGGACATCA ATCGGCTCTCCGACTAC

GACGTGGCTGCTATCGTGCCCCAGTCTTTTCTCAAAGATGATTCTATTGATAATAAA GTGTTGACAAGATCCGATA

AAGCTAGAGGGAAGAGTGATAACGTCCCCTCAGAAGAAGTTGTCAAGAAAATGAAAA ATTATTGGCGGCAGCTG

CTGAACGCCAAACTGATCACACAACGGAAGTTCGATAATCTGACTAAGGCTGAACGA GGTGGCCTGTCTGAGTT

GGATAAAGCCGGCTTCATCAAAAGGCAGCTTGTTGAGACACGCCAGATCACCAAGCA CGTGGCCCAAATTCTCG

ATTCACGCATGAACACCAAGTACGATGAAAATGACAAACTGATTCGAGAGGTGAAAG TTATTACTCTGAAGTCTA

AGCTGGTCTCAGATTTCAGAAAGGACTTTCAGTTTTATAAGGTGAGAGAGATCAACA ATTACCACCATGCGCATG

ATGCCTACCTGAATGCAGTGGTAGGCACTGCACTTATCAAAAAATATCCCAAGCTTG AATCTGAATTTGTTTACG

GAGACTATAAAGTGTACGATGTTAGGAAAATGATCGCAAAGTCTGAGCAGGAAATAG GCAAGGCCACCGCTAAG

TACTTCTTTTACAGCAATATTATGAATTTTTTCAAGACCGAGATTACACTGGCCAAT GGAGAGATTCGGAAGCGAC

CACTTATCGAAACAAACGGAGAAACAGGAGAAATCGTGTGGGACAAGGGTAGGGATT TCGCGACAGTCCGGAA

GGTCCTGTCCATGCCGCAGGTGAACATCGTTAAAAAGACCGAAGTACAGACCGGAGG CTTCTCCAAGGAAAGTA

TCCTCCCGAAAAGGAACAGCGACAAGCTGATCGCACGCAAAAAAGATTGGGACCCCA AGAAATACGGCGGATTC

GATTCTCCTACAGTCGCTTACAGTGTACTGGTTGTGGCCAAAGTGGAGAAAGGGAAG TCTAAAAAACTCAAAAGC

GTCAAGGAACTGCTGGGCATCACAATCATGGAGCGATCAAGCTTCGAAAAAAACCCC ATCGACTTTCTCGAGGC

GAAAGGATATAAAGAGGTCAAAAAAGACCTCATCATTAAGCTTCCCAAGTACTCTCT CTTTGAGCTTGAAAACGG

CCGGAAACGAATGCTCGCTAGTGCGGGCGAGCTGCAGAAAGGTAACGAGCTGGCACT GCCCTCTAAATACGTT

AATTTCTTGTATCTGGCCAGCCACTATGAAAAGCTCAAAGGGTCTCCCGAAGATAAT GAGCAGAAGCAGCTGTTC

GTGGAACAACACAAACACTACCTTGATGAGATCATCGAGCAAATAAGCGAATTCTCC AAAAGAGTGATCCTCGCC

GACGCTAACCTCGATAAGGTGCTTTCTGCTTACAATAAGCACAGGGATAAGCCCATC AGGGAGCAGGCAGAAAA

CATTATCCACTTGTTTACTCTGACCAACTTGGGCGCGCCTGCAGCCTTCAAGTACTT CGACACCACCATAGACAG AAAGCGGTACACCTCTACAAAGGAGGTCCTGGACGCCACACTGATTCATCAGTCAATTAC GGGGCTCTATGAAA

CAAGAATCGACCTCTCTCAGCTCGGTGGAGACAGCAGGGCTGACCCCAAGAAGAAGA GGAAGGTGGAGGCCA

GCGGTTCCGGACGGGCTGACGCATTGGACGATTTTGATCTGGATATGCTGGGAAGTG ACGCCCTCGATGATTTT

GACCTTGACATGCTTGGTTCGGATGCCCTTGATGACTTTGACCTCGACATGCTCGGC AGTGACGCCCTTGATGA

TTTCGACCTGGACATGCTGATTAACTCTAGATAAGAATTCAATAAAAGATCTTTATT TTCATTAGATCTGTGTGTTG

GTTTTTTGTGTGCGGCCGCAGGAACCCCTAGTGATGGAGTTGGCCACTCCCTCTCTG CGCGCTCGCTCGCTCAC

TGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGGGCTTTGCCCGGGCGGCCTCAGT GAGCGAGCGAGCGC

GCAGCTGCCTGCAGGGGCGCCTGATGCGGTATTTTCTCCTTACGCATCTGTGCGGTA TTTCACACCGCATACGT

CAAAGCAACCATAGTACGCGCCCTGTAGCGGCGCATTAAGCGCGGCGGGTGTGGTGG TTACGCGCAGCGTGA

CCGCTACACTTGCCAGCGCCCTAGCGCCCGCTCCTTTCGCTTTCTTCCCTTCCTTTC TCGCCACGTTCGCCGGC

TTTCCCCGTCAAGCTCTAAATCGGGGGCTCCCTTTAGGGTTCCGATTTAGTGCTTTA CGGCACCTCGACCCCAAA

AAACTTGATTTGGGTGATGGTTCACGTAGTGGGCCATCGCCCTGATAGACGGTTTTT CGCCCTTTGACGTTGGA

GTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAACTGGAACAACACTCAACCCTAT CTCGGGCTATTCTTTTGAT

TTATAAGGGATTTTGCCGATTTCGGCCTATTGGTTAAAAAATGAGCTGATTTAACAA AAATTTAACGCGAATTTTAA

CAAAATATTAACGTTTACAATTTTATGGTGCACTCTCAGTACAATCTGCTCTGATGC CGCATAGTTAAGCCAGCCC

CGACACCCGCCAACACCCGCTGACGCGCCCTGACGGGCTTGTCTGCTCCCGGCATCC GCTTACAGACAAGCTG

TGACCGTCTCCGGGAGCTGCATGTGTCAGAGGTTTTCACCGTCATCACCGAAACGCG CGAGACGAAAGGGCCT

CGTGATACGCCTATTTTTATAGGTTAATGTCATGATAATAATGGTTTCTTAGACGTC AGGTGGCACTTTTCGGGGA

AATGTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTATCCG CTCATGAGACAATAACCCT

GATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTCCGTG TCGCCCTTATTCCCTTTTTT

GCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAAAAGAT GCTGAAGATCAGTTGGGT

GCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAGTTTT CGCCCCGAAGAACGTTT

TCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTATTGA CGCCGGGCAAGAGCAACT

CGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCACAGA AAAGCATCTTACGGATGG

CATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTGCGGC CAACTTACTTCTGACAAC

GATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATGTAAC TCGCCTTGATCGTTGGG

AACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCTGTAG CAATGGCAACAACGTT

GCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAATAGA CTGGATGGAGGCGGATAA

AGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCTGATAA ATCTGGAGCCGGTGAGC

GTGGAAGCCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCGTATCG TAGTTATCTACACGAC

GGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTGCCTC ACTGATTAAGCATTGGT

AACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCATTTTT AATTTAAAAGGATCTAGGTG

AAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTCCAC TGAGCGTCAGACCCCGTAG

AAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGCTTGC AAACAAAAAAACCACCGCT

ACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGGTAAC TGGCTTCAGCAGAGCGC

AGATACCAAATACTGTCCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAGAACT CTGTAGCACCGCCTACAT

ACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCGTGTC TTACCGGGTTGGACTCA

AGACGATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTGCACA CAGCCCAGCTTGGAG

CGAACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCCACG CTTCCCGAAGGGAGAA

AGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGGAGC TTCCAGGGGGAAAC

GCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGATTT TTGTGATGCTCGTCAGGG

GGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCCTTT TGCTGGCCTTTTGCTCA

CATGT pAAV-U6gRNA(Kcna 1-sp Mouse sgRNA19)-U6gRNA(Gabra5-sp Mouse sgRNA3)-CaMKII2a ttA Tomato used in in vivo experiments (SEQ ID NO: 6)

TAACATTATGGCCTTAGGTCACTTCATCTCCATGGGGTTCTTCTTCTGATTTTCTAG AAAATGAGATGGGGGTGCA

GAGAGCTTCCTCAGTGACCTGCCCAGGGTCACATCAGAAATGTCAGAGCTAGAACTT GAACTCAGATTACTAATC TTAAATTCCATGCCTTGGGGGCATGCAAGTACGATATACAGAAGGAGTGAACTCATTAGG GCAGATGACCAATG AGTTTAGGAAAGAAGAGTCCAGGGCAGGGTACATCTACACCACCCGCCCAGCCCTGGGTG AGTCCAGCCACGT TCACCTCATTATAGTTGCCTCTCTCCAGTCCTACCTTGACGGGAAGCACAAGCAGAAACT GGGACAGGAGCCCC AGGAGACCAAATCTTCATGGTCCCTCTGGGAGGATGGGTGGGGAGAGCTGTGGCAGAGGC CTCAGGAGGGGC CCTGCTGCTCAGTGGTGACAGATAGGGGTGAGAAAGCAGACAGAGTCATTCCGTCAGCAT TCTGGGTCTGTTTG GTACTTCTTCTCACGCTAAGGTGGCGGTGTGATATGCACAATGGCTAAAAAGCAGGGAGA GCTGGAAAGAAACA

AGGACAGAGACAGAGGCCAAGTCAACCAGACCAATTCCCAGAGGAAGCAAAGAAACC ATTACAGAGACTACAAG

GGGGAAGGGAAGGAGAGATGAATTAGCTTCCCCTGTAAACCTTAGAACCCAGCTGTT GCCAGGGCAACGGGGC

AATACCTGTCTCTTCAGAGGAGATGAAGTTGCCAGGGTAACTACATCCTGTCTTTCT CAAGGACCATCCCAGAAT

GTGGCACCCACTAGCCGTTACCATAGCAACTGCCTCTTTGCCCCACTTAATCCCATC CCGTCTGTTAAAAGGGC

CCTATAGTTGGAGGTGGGGGAGGTAGGAAGAGCGATGATCACTTGTGGACTAAGTTT GTTCGCATCCCCTTCTC

CAACCCCCTCAGTACATCACCCTGGGGGAACAGGGTCCACTTGCTCCTGGGCCCACA CAGTCCTGCAGTATTGT

GTATATAAGGCCAGGGCAAAGAGGAGCAGGTTTTAAAGTGAAAGGCAGGCAGGTGTT GGGGAGGCAGTTACCG

GGGCAACGGGAACAGGGCGTTTCGGAGGTGGTTGCCATGGGGACCTGGATGCTGACG AAGGCTCGCGAGGCT

GTGAGCAGCCACAGTGCCCTGCTCAGAAGCCCCAAGCTCGTCAGTCAAGCCGGTTCT CCGTTTGCACTCAGGA

GCACGGGCAGGCGAGTGGCCCCTAGTTCTGGGGGCAGCGGTACCGCCACCATGTCTA GACTGGACAAGAGCA

AAGTCATAAACGGCGCTCTGGAATTACTCAATGGAGTCGGTATCGAAGGCCTGACGA CAAGGAAACTCGCTCAA

AAGCTGGGAGTTGAGCAGCCTACCCTGTACTGGCACGTGAAGAACAAGCGGGCCCTG CTCGATGCCCTGCCAA

TCGAGATGCTGGACAGGCATCATACCCACTTCTGCCCCCTGGAAGGCGAGTCATGGC AAGACTTTCTGCGGAAC

AACGCCAAGTCATTCCGCTGTGCTCTCCTCTCACATCGCGACGGGGCTAAAGTGCAT CTCGGCACCCGCCCAAC

AGAGAAACAGTACGAAACCCTGGAAAATCAGCTCGCGTTCCTGTGTCAGCAAGGCTT CTCCCTGGAGAACGCAC

TGTACGCTCTGTCCGCCGTGGGCCACTTTACACTGGGCTGCGTATTGGAGGAACAGG AGCATCAAGTAGCAAAA

GAGGAAAGAGAGACACCTACCACCGATTCTATGCCCCCACTTCTGAGACAAGCAATT GAGCTGTTCGACCGGCA

GGGAGCCGAACCTGCCTTCCTTTTCGGCCTGGAACTAATCATATGTGGCCTGGAGAA ACAGCTAAAGTGCGAAA

GCGGCGGGCCGGCCGACGCCCTTGACGATTTTGACTTAGACATGCTCCCAGCCGATG CCCTTGACGACTTTGA

CCTTGATATGCTGCCTGCTGACGCTCTTGACGATTTTGACCTTGACATGCTCCCCGG GGGATCCGCTGAGGGTC

GGGGCTCTCTGCTCACATGTGGCGACGTCGAGGAGAATCCCGGACCGGCCCCGGGGT CGACAATGGTGTCTA

AGGGTGAGGAAGTAATTAAGGAGTTTATGAGATTCAAAGTTAGAATGGAGGGTAGCA TGAACGGGCACGAGTTT

GAAATTGAAGGTGAGGGTGAAGGAAGACCATATGAGGGCACACAAACCGCCAAGCTC AAGGTTACCAAAGGTG

GCCCCCTTCCTTTCGCCTGGGACATCCTCAGCCCTCAATTCATGTACGGTAGCAAGG CTTACGTCAAACACCCT

GCTGATATACCTGATTACAAAAAACTGTCATTTCCTGAAGGATTTAAGTGGGAACGA GTAATGAATTTTGAGGATG

GTGGGCTGGTCACTGTCACGCAAGACTCCTCTCTGCAGGACGGCACCCTGATTTACA AGGTGAAGATGCGCGG

AACAAATTTTCCCCCCGATGGCCCCGTGATGCAGAAGAAGACCATGGGGTGGGAGGC CTCTACAGAACGACTG

TACCCCCGCGATGGCGTTCTTAAAGGCGAAATCCATCAGGCGCTTAAACTCAAAGAT GGCGGGCACTACCTGGT

TGAGTTCAAAACTATATATATGGCCAAAAAGCCGGTTCAGCTGCCTGGCTACTACTA CGTGGACACCAAGTTGGA

CATCACGAGTCACAACGAGGACTACACAATCGTCGAGCAGTACGAACGCTCAGAAGG TCGGCATCACCTGTTCT

TGTATGGCATGGATGAGCTGTATAAGTAAATCGATACCGAGCGCTGCTCGAGAGATC TACGGGTGGCATCCCTG

TGACCCCTCCCCAGTGCCTCTCCTGGCCCTGGAAGTTGCCACTCCAGTGCCCACCAG CCTTGTCCTAATAAAAT

TAAGTTGCATCATTTTGTCTGACTAGGTGTCCTTCTATAATATTATGGGGTGGAGGG GGGTGGTATGGAGCAAGG

GGCAAGTTGGGAAGACAACCTGTAGGGCCTGCGGGGTCTATTGGGAACCAAGCTGGA GTGCAGTGGCACAATC

TTGGCTCACTGCAATCTCCGCCTCCTGGGTTCAAGCGATTCTCCTGCCTCAGCCTCC CGAGTTGTTGGGATTCC

AGGCATGCATGACCAGGCTCAGCTAATTTTTGTTTTTTTGGTAGAGACGGGGTTTCA CCATATTGGCCAGGCTGG

TCTCCAACTCCTAATCTCAGGTGATCTACCCACCTTGGCCTCCCAAATTGCTGGGAT TACAGGCGTGAACCACTG

CTCCCTTCCCTGTCCTTCTGATTTTGTAGGTAACCACGTGCGGACCGAGCGGCCGCA GGAACCCCTAGTGATGG

AGTTGGCCACTCCCTCTCTGCGCGCTCGCTCGCTCACTGAGGCCGGGCGACCAAAGG TCGCCCGACGCCCGG

GCTTTGCCCGGGCGGCCTCAGTGAGCGAGCGAGCGCGCAGCTGCCTGCAGGGGCGCC TGATGCGGTATTTTC

TCCTTACGCATCTGTGCGGTATTTCACACCGCATACGTCAAAGCAACCATAGTACGC GCCCTGTAGCGGCGCAT

TAAGCGCGGCGGGTGTGGTGGTTACGCGCAGCGTGACCGCTACACTTGCCAGCGCCC TAGCGCCCGCTCCTTT

CGCTTTCTTCCCTTCCTTTCTCGCCACGTTCGCCGGCTTTCCCCGTCAAGCTCTAAA TCGGGGGCTCCCTTTAGG

GTTCCGATTTAGTGCTTTACGGCACCTCGACCCCAAAAAACTTGATTTGGGTGATGG TTCACGTAGTGGGCCATC

GCCCTGATAGACGGTTTTTCGCCCTTTGACGTTGGAGTCCACGTTCTTTAATAGTGG ACTCTTGTTCCAAACTGG

AACAACACTCAACCCTATCTCGGGCTATTCTTTTGATTTATAAGGGATTTTGCCGAT TTCGGCCTATTGGTTAAAA

AATGAGCTGATTTAACAAAAATTTAACGCGAATTTTAACAAAATATTAACGTTTACA ATTTTATGGTGCACTCTCAG

TACAATCTGCTCTGATGCCGCATAGTTAAGCCAGCCCCGACACCCGCCAACACCCGC TGACGCGCCCTGACGG

GCTTGTCTGCTCCCGGCATCCGCTTACAGACAAGCTGTGACCGTCTCCGGGAGCTGC ATGTGTCAGAGGTTTTC

ACCGTCATCACCGAAACGCGCGAGACGAAAGGGCCTCGTGATACGCCTATTTTTATA GGTTAATGTCATGATAAT

AATGGTTTCTTAGACGTCAGGTGGCACTTTTCGGGGAAATGTGCGCGGAACCCCTAT TTGTTTATTTTTCTAAATA

CATTCAAATATGTATCCGCTCATGAGACAATAACCCTGATAAATGCTTCAATAATAT TGAAAAAGGAAGAGTATGA GTATTCAACATTTCCGTGTCGCCCTTATTCCCTTTTTTGCGGCATTTTGCCTTCCTGTTT TTGCTCACCCAGAAAC GCTGGTGAAAGTAAAAGATGCTGAAGATCAGTTGGGTGCACGAGTGGGTTACATCGAACT GGATCTCAACAGCG GTAAGATCCTTGAGAGTTTTCGCCCCGAAGAACGTTTTCCAATGATGAGCACTTTTAAAG TTCTGCTATGTGGCG CGGTATTATCCCGTATTGACGCCGGGCAAGAGCAACTCGGTCGCCGCATACACTATTCTC AGAATGACTTGGTT GAGTACTCACCAGTCACAGAAAAGCATCTTACGGATGGCATGACAGTAAGAGAATTATGC AGTGCTGCCATAAC CATGAGTGATAACACTGCGGCCAACTTACTTCTGACAACGATCGGAGGACCGAAGGAGCT AACCGCTTTTTTGC ACAACATGGGGGATCATGTAACTCGCCTTGATCGTTGGGAACCGGAGCTGAATGAAGCCA TACCAAACGACGAG CGTGACACCACGATGCCTGTAGCAATGGCAACAACGTTGCGCAAACTATTAACTGGCGAA CTACTTACTCTAGCT TCCCGGCAACAATTAATAGACTGGATGGAGGCGGATAAAGTTGCAGGACCACTTCTGCGC TCGGCCCTTCCGG CTGGCTGGTTTATTGCTGATAAATCTGGAGCCGGTGAGCGTGGGTCTCGCGGTATCATTG CAGCACTGGGGCC AGATGGTAAGCCCTCCCGTATCGTAGTTATCTACACGACGGGGAGTCAGGCAACTATGGA TGAACGAAATAGAC AGATCGCTGAGATAGGTGCCTCACTGATTAAGCATTGGTAACTGTCAGACCAAGTTTACT CATATATACTTTAGAT TGATTTAAAACTTCATTTTTAATTTAAAAGGATCTAGGTGAAGATCCTTTTTGATAATCT CATGACCAAAATCCCTT AACGTGAGTTTTCGTTCCACTGAGCGTCAGACCCCGTAGAAAAGATCAAAGGATCTTCTT GAGATCCTTTTTTTCT GCGCGTAATCTGCTGCTTGCAAACAAAAAAACCACCGCTACCAGCGGTGGTTTGTTTGCC GGATCAAGAGCTAC CAACTCTTTTTCCGAAGGTAACTGGCTTCAGCAGAGCGCAGATACCAAATACTGTCCTTC TAGTGTAGCCGTAGT TAGGCCACCACTTCAAGAACTCTGTAGCACCGCCTACATACCTCGCTCTGCTAATCCTGT TACCAGTGGCTGCTG CCAGTGGCGATAAGTCGTGTCTTACCGGGTTGGACTCAAGACGATAGTTACCGGATAAGG CGCAGCGGTCGGG CTGAACGGGGGGTTCGTGCACACAGCCCAGCTTGGAGCGAACGACCTACACCGAACTGAG ATACCTACAGCGT GAGCTATGAGAAAGCGCCACGCTTCCCGAAGGGAGAAAGGCGGACAGGTATCCGGTAAGC GGCAGGGTCGGA ACAGGAGAGCGCACGAGGGAGCTTCCAGGGGGAAACGCCTGGTATCTTTATAGTCCTGTC GGGTTTCGCCACC TCTGACTTGAGCGTCGATTTTTGTGATGCTCGTCAGGGGGGCGGAGCCTATGGAAAAACG CCAGCAACGCGGC CTTTTTACGGTTCCTGGCCTTTTGCTGGCCTTTTGCTCACATGTCCTGCAGGCAGCTGCG CGCTCGCTCGCTCA CTGAGGCCGCCCGGGCAAAGCCCGGGCGTCGGGCGACCTTTGGTCGCCCGGCCTCAGTGA GCGAGCGAGCG CGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCCTGCGGCCGCACGCGTGAGGGC CTATTTCCCATGA TTCCTTCATATTTGCATATACGATACAAGGCTGTTAGAGAGATAATTGGAATTAATTTGA CTGTAAACACAAAGATA TTAGTACAAAATACGTGACGTAGAAAGTAATAATTTCTTGGGTAGTTTGCAGTTTTAAAA TTATGTTTTAAAATGGA CTATCATATGCTTACCGTAACTTGAAAGTATTTCGATTTCTTGGCTTTATATATCTTGTG GAAAGGACGAAACACC AGTCAATGATCACATCCTCCGTTTTAGAGCTAGAAATAGCAAGTTAAAATAAGGCTAGTC CGTTATCAACTTGAAA AAGTGGCACCGAGTCGGTGCTTTTTTTCTAGCTTAGAGGGCCTATTTCCCATGATTCCTT CATATTTGCATATACG ATACAAGGCTGTTAGAGAGATAATTAGAATTAATTTGACTGTAAACACAAAGATATTAGT ACAAAATACGTGACGT AGAAAGTAATAATTTCTTGGGTAGTTTGCAGTTTTAAAATTATGTTTTAAAATGGACTAT CATATGCTTACCGTAAC TTGAAAGTATTTCGATTTCTTGGCTTTATATATCTTGTGGAAAGGACGAAACACCGAACA TGGTCTTTCCCGAAGC GTTTTAGAGCTAGAAATAGCAAGTTAAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGT GGCACCGAGTCGGTG CTTTTTTT pAAV2-U6-aRNA(Kcna 1-sp-sgRNA19)-CaMKIIA ttA Tomato used in in vivo experiments (SEQ ID NO: 7)

CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAGCCCGGGC GTCGGGCGACCTTTG GTCGCCCGGCCTCAGTGAGCGAGCGAGCGCGCAGAGAGGGAGTGGCCAACTCCATCACTA GGGGTTCCTGCG GCCGCACGCGTGAGGGCCTATTTCCCATGATTCCTTCATATTTGCATATACGATACAAGG CTGTTAGAGAGATAA TTGGAATTAATTTGACTGTAAACACAAAGATATTAGTACAAAATACGTGACGTAGAAAGT AATAATTTCTTGGGTA GTTTGCAGTTTTAAAATTATGTTTTAAAATGGACTATCATATGCTTACCGTAACTTGAAA GTATTTCGATTTCTTGG CTTTATATATCTTGTGGAAAGGACGAAACACCAGTCAATGATCACATCCTCCGTTTTAGA GCTAGAAATAGCAAGT TAAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTTTTTTTC TAGCTTAATTAACATT ATGGCCTTAGGTCACTTCATCTCCATGGGGTTCTTCTTCTGATTTTCTAGAAAATGAGAT GGGGGTGCAGAGAGC TTCCTCAGTGACCTGCCCAGGGTCACATCAGAAATGTCAGAGCTAGAACTTGAACTCAGA TTACTAATCTTAAATT CCATGCCTTGGGGGCATGCAAGTACGATATACAGAAGGAGTGAACTCATTAGGGCAGATG ACCAATGAGTTTAG GAAAGAAGAGTCCAGGGCAGGGTACATCTACACCACCCGCCCAGCCCTGGGTGAGTCCAG CCACGTTCACCTC ATTATAGTTGCCTCTCTCCAGTCCTACCTTGACGGGAAGCACAAGCAGAAACTGGGACAG GAGCCCCAGGAGAC CAAATCTTCATGGTCCCTCTGGGAGGATGGGTGGGGAGAGCTGTGGCAGAGGCCTCAGGA GGGGCCCTGCTG CTCAGTGGTGACAGATAGGGGTGAGAAAGCAGACAGAGTCATTCCGTCAGCATTCTGGGT CTGTTTGGTACTTC TTCTCACGCTAAGGTGGCGGTGTGATATGCACAATGGCTAAAAAGCAGGGAGAGCTGGAA AGAAACAAGGACA GAGACAGAGGCCAAGTCAACCAGACCAATTCCCAGAGGAAGCAAAGAAACCATTACAGAG ACTACAAGGGGGA AGGGAAGGAGAGATGAATTAGCTTCCCCTGTAAACCTTAGAACCCAGCTGTTGCCAGGGC AACGGGGCAATACC

TGTCTCTTCAGAGGAGATGAAGTTGCCAGGGTAACTACATCCTGTCTTTCTCAAGGA CCATCCCAGAATGTGGCA

CCCACTAGCCGTTACCATAGCAACTGCCTCTTTGCCCCACTTAATCCCATCCCGTCT GTTAAAAGGGCCCTATAG

TTGGAGGTGGGGGAGGTAGGAAGAGCGATGATCACTTGTGGACTAAGTTTGTTCGCA TCCCCTTCTCCAACCCC

CTCAGTACATCACCCTGGGGGAACAGGGTCCACTTGCTCCTGGGCCCACACAGTCCT GCAGTATTGTGTATATA

AGGCCAGGGCAAAGAGGAGCAGGTTTTAAAGTGAAAGGCAGGCAGGTGTTGGGGAGG CAGTTACCGGGGCAA

CGGGAACAGGGCGTTTCGGAGGTGGTTGCCATGGGGACCTGGATGCTGACGAAGGCT CGCGAGGCTGTGAGC

AGCCACAGTGCCCTGCTCAGAAGCCCCAAGCTCGTCAGTCAAGCCGGTTCTCCGTTT GCACTCAGGAGCACGG

GCAGGCGAGTGGCCCCTAGTTCTGGGGGCAGCGGTACCGCCACCATGTCTAGACTGG ACAAGAGCAAAGTCAT

AAACGGCGCTCTGGAATTACTCAATGGAGTCGGTATCGAAGGCCTGACGACAAGGAA ACTCGCTCAAAAGCTGG

GAGTTGAGCAGCCTACCCTGTACTGGCACGTGAAGAACAAGCGGGCCCTGCTCGATG CCCTGCCAATCGAGAT

GCTGGACAGGCATCATACCCACTTCTGCCCCCTGGAAGGCGAGTCATGGCAAGACTT TCTGCGGAACAACGCC

AAGTCATTCCGCTGTGCTCTCCTCTCACATCGCGACGGGGCTAAAGTGCATCTCGGC ACCCGCCCAACAGAGAA

ACAGTACGAAACCCTGGAAAATCAGCTCGCGTTCCTGTGTCAGCAAGGCTTCTCCCT GGAGAACGCACTGTACG

CTCTGTCCGCCGTGGGCCACTTTACACTGGGCTGCGTATTGGAGGAACAGGAGCATC AAGTAGCAAAAGAGGA

AAGAGAGACACCTACCACCGATTCTATGCCCCCACTTCTGAGACAAGCAATTGAGCT GTTCGACCGGCAGGGAG

CCGAACCTGCCTTCCTTTTCGGCCTGGAACTAATCATATGTGGCCTGGAGAAACAGC TAAAGTGCGAAAGCGGC

GGGCCGGCCGACGCCCTTGACGATTTTGACTTAGACATGCTCCCAGCCGATGCCCTT GACGACTTTGACCTTGA

TATGCTGCCTGCTGACGCTCTTGACGATTTTGACCTTGACATGCTCCCCGGGGGATC CGCTGAGGGTCGGGGC

TCTCTGCTCACATGTGGCGACGTCGAGGAGAATCCCGGACCGGCCCCGGGGTCGACA ATGGTGTCTAAGGGTG

AGGAAGTAATTAAGGAGTTTATGAGATTCAAAGTTAGAATGGAGGGTAGCATGAACG GGCACGAGTTTGAAATTG

AAGGTGAGGGTGAAGGAAGACCATATGAGGGCACACAAACCGCCAAGCTCAAGGTTA CCAAAGGTGGCCCCCT

TCCTTTCGCCTGGGACATCCTCAGCCCTCAATTCATGTACGGTAGCAAGGCTTACGT CAAACACCCTGCTGATAT

ACCTGATTACAAAAAACTGTCATTTCCTGAAGGATTTAAGTGGGAACGAGTAATGAA TTTTGAGGATGGTGGGCT

GGTCACTGTCACGCAAGACTCCTCTCTGCAGGACGGCACCCTGATTTACAAGGTGAA GATGCGCGGAACAAATT

TTCCCCCCGATGGCCCCGTGATGCAGAAGAAGACCATGGGGTGGGAGGCCTCTACAG AACGACTGTACCCCCG

CGATGGCGTTCTTAAAGGCGAAATCCATCAGGCGCTTAAACTCAAAGATGGCGGGCA CTACCTGGTTGAGTTCA

AAACTATATATATGGCCAAAAAGCCGGTTCAGCTGCCTGGCTACTACTACGTGGACA CCAAGTTGGACATCACGA

GTCACAACGAGGACTACACAATCGTCGAGCAGTACGAACGCTCAGAAGGTCGGCATC ACCTGTTCTTGTATGGC

ATGGATGAGCTGTATAAGTAAATCGATACCGAGCGCTGCTCGAGAGATCTACGGGTG GCATCCCTGTGACCCCT

CCCCAGTGCCTCTCCTGGCCCTGGAAGTTGCCACTCCAGTGCCCACCAGCCTTGTCC TAATAAAATTAAGTTGC

ATCATTTTGTCTGACTAGGTGTCCTTCTATAATATTATGGGGTGGAGGGGGGTGGTA TGGAGCAAGGGGCAAGT

TGGGAAGACAACCTGTAGGGCCTGCGGGGTCTATTGGGAACCAAGCTGGAGTGCAGT GGCACAATCTTGGCTC

ACTGCAATCTCCGCCTCCTGGGTTCAAGCGATTCTCCTGCCTCAGCCTCCCGAGTTG TTGGGATTCCAGGCATG

CATGACCAGGCTCAGCTAATTTTTGTTTTTTTGGTAGAGACGGGGTTTCACCATATT GGCCAGGCTGGTCTCCAA

CTCCTAATCTCAGGTGATCTACCCACCTTGGCCTCCCAAATTGCTGGGATTACAGGC GTGAACCACTGCTCCCTT

CCCTGTCCTTCTGATTTTGTAGGTAACCACGTGCGGACCGAGCGGCCGCAGGAACCC CTAGTGATGGAGTTGG

CCACTCCCTCTCTGCGCGCTCGCTCGCTCACTGAGGCCGGGCGACCAAAGGTCGCCC GACGCCCGGGCTTTG

CCCGGGCGGCCTCAGTGAGCGAGCGAGCGCGCAGCTGCCTGCAGGGGCGCCTGATGC GGTATTTTCTCCTTA

CGCATCTGTGCGGTATTTCACACCGCATACGTCAAAGCAACCATAGTACGCGCCCTG TAGCGGCGCATTAAGCG

CGGCGGGTGTGGTGGTTACGCGCAGCGTGACCGCTACACTTGCCAGCGCCCTAGCGC CCGCTCCTTTCGCTTT

CTTCCCTTCCTTTCTCGCCACGTTCGCCGGCTTTCCCCGTCAAGCTCTAAATCGGGG GCTCCCTTTAGGGTTCC

GATTTAGTGCTTTACGGCACCTCGACCCCAAAAAACTTGATTTGGGTGATGGTTCAC GTAGTGGGCCATCGCCC

TGATAGACGGTTTTTCGCCCTTTGACGTTGGAGTCCACGTTCTTTAATAGTGGACTC TTGTTCCAAACTGGAACA

ACACTCAACCCTATCTCGGGCTATTCTTTTGATTTATAAGGGATTTTGCCGATTTCG GCCTATTGGTTAAAAAATG

AGCTGATTTAACAAAAATTTAACGCGAATTTTAACAAAATATTAACGTTTACAATTT TATGGTGCACTCTCAGTACA

ATCTGCTCTGATGCCGCATAGTTAAGCCAGCCCCGACACCCGCCAACACCCGCTGAC GCGCCCTGACGGGCTT

GTCTGCTCCCGGCATCCGCTTACAGACAAGCTGTGACCGTCTCCGGGAGCTGCATGT GTCAGAGGTTTTCACCG

TCATCACCGAAACGCGCGAGACGAAAGGGCCTCGTGATACGCCTATTTTTATAGGTT AATGTCATGATAATAATG

GTTTCTTAGACGTCAGGTGGCACTTTTCGGGGAAATGTGCGCGGAACCCCTATTTGT TTATTTTTCTAAATACATT

CAAATATGTATCCGCTCATGAGACAATAACCCTGATAAATGCTTCAATAATATTGAA AAAGGAAGAGTATGAGTAT

TCAACATTTCCGTGTCGCCCTTATTCCCTTTTTTGCGGCATTTTGCCTTCCTGTTTT TGCTCACCCAGAAACGCTG

GTGAAAGTAAAAGATGCTGAAGATCAGTTGGGTGCACGAGTGGGTTACATCGAACTG GATCTCAACAGCGGTAA GATCCTTGAGAGTTTTCGCCCCGAAGAACGTTTTCCAATGATGAGCACTTTTAAAGTTCT GCTATGTGGCGCGGT

ATTATCCCGTATTGACGCCGGGCAAGAGCAACTCGGTCGCCGCATACACTATTCTCA GAATGACTTGGTTGAGT

ACTCACCAGTCACAGAAAAGCATCTTACGGATGGCATGACAGTAAGAGAATTATGCA GTGCTGCCATAACCATGA

GTGATAACACTGCGGCCAACTTACTTCTGACAACGATCGGAGGACCGAAGGAGCTAA CCGCTTTTTTGCACAAC

ATGGGGGATCATGTAACTCGCCTTGATCGTTGGGAACCGGAGCTGAATGAAGCCATA CCAAACGACGAGCGTG

ACACCACGATGCCTGTAGCAATGGCAACAACGTTGCGCAAACTATTAACTGGCGAAC TACTTACTCTAGCTTCCC

GGCAACAATTAATAGACTGGATGGAGGCGGATAAAGTTGCAGGACCACTTCTGCGCT CGGCCCTTCCGGCTGG

CTGGTTTATTGCTGATAAATCTGGAGCCGGTGAGCGTGGGTCTCGCGGTATCATTGC AGCACTGGGGCCAGATG

GTAAGCCCTCCCGTATCGTAGTTATCTACACGACGGGGAGTCAGGCAACTATGGATG AACGAAATAGACAGATC

GCTGAGATAGGTGCCTCACTGATTAAGCATTGGTAACTGTCAGACCAAGTTTACTCA TATATACTTTAGATTGATT

TAAAACTTCATTTTTAATTTAAAAGGATCTAGGTGAAGATCCTTTTTGATAATCTCA TGACCAAAATCCCTTAACGT

GAGTTTTCGTTCCACTGAGCGTCAGACCCCGTAGAAAAGATCAAAGGATCTTCTTGA GATCCTTTTTTTCTGCGC

GTAATCTGCTGCTTGCAAACAAAAAAACCACCGCTACCAGCGGTGGTTTGTTTGCCG GATCAAGAGCTACCAACT

CTTTTTCCGAAGGTAACTGGCTTCAGCAGAGCGCAGATACCAAATACTGTCCTTCTA GTGTAGCCGTAGTTAGGC

CACCACTTCAAGAACTCTGTAGCACCGCCTACATACCTCGCTCTGCTAATCCTGTTA CCAGTGGCTGCTGCCAGT

GGCGATAAGTCGTGTCTTACCGGGTTGGACTCAAGACGATAGTTACCGGATAAGGCG CAGCGGTCGGGCTGAA

CGGGGGGTTCGTGCACACAGCCCAGCTTGGAGCGAACGACCTACACCGAACTGAGAT ACCTACAGCGTGAGCT

ATGAGAAAGCGCCACGCTTCCCGAAGGGAGAAAGGCGGACAGGTATCCGGTAAGCGG CAGGGTCGGAACAGG

AGAGCGCACGAGGGAGCTTCCAGGGGGAAACGCCTGGTATCTTTATAGTCCTGTCGG GTTTCGCCACCTCTGA

CTTGAGCGTCGATTTTTGTGATGCTCGTCAGGGGGGCGGAGCCTATGGAAAAACGCC AGCAACGCGGCCTTTTT

ACGGTTCCTGGCCTTTTGCTGGCCTTTTGCTCACATGT pKLV-U6gRNA(Gabra5-sp sgRNA1) used in in vitro for qPCR experiments (SEQ ID NO: 8)

CTAAATTGTAAGCGTTAATATTTTGTTAAAATTCGCGTTAAATTTTTGTTAAATCAG CTCATTTTTTAACCAATAGGC

CGAAATCGGCAAAATCCCTTATAAATCAAAAGAATAGACCGAGATAGGGTTGAGTGT TGTTCCAGTTTGGAACAA

GAGTCCACTATTAAAGAACGTGGACTCCAACGTCAAAGGGCGAAAAACCGTCTATCA GGGCGATGGCCCACTAC

GTGAACCATCACCCTAATCAAGTTTTTTGGGGTCGAGGTGCCGTAAAGCACTAAATC GGAACCCTAAAGGGAGC

CCCCGATTTAGAGCTTGACGGGGAAAGCCGGCGAACGTGGCGAGAAAGGAAGGGAAG AAAGCGAAAGGAGCG

GGCGCTAGGGCGCTGGCAAGTGTAGCGGTCACGCTGCGCGTAACCACCACACCCGCC GCGCTTAATGCGCCG

CTACAGGGCGCGTCCCATTCGCCATTCAGGCTGCGCAACTGTTGGGAAGGGCGATCG GTGCGGGCCTCTTCGC

TATTACGCCAGCTGGCGAAAGGGGGATGTGCTGCAAGGCGATTAAGTTGGGTAACGC CAGGGTTTTCCCAGTC

ACGACGTTGTAAAACGACGGCCAGTGAGCGCGCGTAATACGACTCACTATAGGGCGA ATTGACTAGTTATTAAT

AGTAATCAATTACGGGGTCATTAGTTCATAGCCCATATATGGAGTTCCGCGTTACAT AACTTACGGTAAATGGCC

CGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGACGTCAATAATGACGTATGTTC CCATAGTAACGCCAATA

GGGACTTTCCATTGACGTCAATGGGTGGAGTATTTACGGTAAACTGCCCACTTGGCA GTACATCAAGTGTATCAT

ATGCCAAGTACGCCCCCTATTGACGTCAATGACGGTAAATGGCCCGCCTGGCATTAT GCCCAGTACATGACCTT

ATGGGACTTTCCTACTTGGCAGTACATCTACGTATTAGTCATCGCTATTACCATGGT GATGCGGTTTTGGCAGTA

CATCAATGGGCGTGGATAGCGGTTTGACTCACGGGGATTTCCAAGTCTCCACCCCAT TGACGTCAATGGGAGTT

TGTTTTGGCACCAAAATCAACGGGACTTTCCAAAATGTCGTAACAACTCCGCCCCAT TGACGCAAATGGGCGGTA

GGCGTGTACGGTGGGAGGTCTATATAAGCAGCGCGTTTTGCCTGTACTGGGTCTCTC TGGTTAGACCAGATCTG

AGCCTGGGAGCTCTCTGGCTAACTAGGGAACCCACTGCTTAAGCCTCAATAAAGCTT GCCTTGAGTGCTTCAAG

TAGTGTGTGCCCGTCTGTTGTGTGACTCTGGTAACTAGAGATCCCTCAGACCCTTTT AGTCAGTGTGGAAAATCT

CTAGCAGTGGCGCCCGAACAGGGACTTGAAAGCGAAAGGGAAACCAGAGGAGCTCTC TCGACGCAGGACTCG

GCTTGCTGAAGCGCGCACGGCAAGAGGCGAGGGGCGGCGACTGGTGAGTACGCCAAA AATTTTGACTAGCGG

AGGCTAGAAGGAGAGAGATGGGTGCGAGAGCGTCAGTATTAAGCGGGGGAGAATTAG ATCGCGATGGGAAAAA

ATTCGGTTAAGGCCAGGGGGAAAGAAAAAATATAAATTAAAACATATAGTATGGGCA AGCAGGGAGCTAGAACG

ATTCGCAGTTAATCCTGGCCTGTTAGAAACATCAGAAGGCTGTAGACAAATACTGGG ACAGCTACAACCATCCCT

TCAGACAGGATCAGAAGAACTTAGATCATTATATAATACAGTAGCAACCCTCTATTG TGTGCATCAAAGGATAGA

GATAAAAGACACCAAGGAAGCTTTAGACAAGATAGAGGAAGAGCAAAACAAAAGTAA GACCACCGCACAGCAAG

CGGCCGGCCGCGCTGATCTTCAGACCTGGAGGAGGAGATATGAGGGACAATTGGAGA AGTGAATTATATAAATA

TAAAGTAGTAAAAATTGAACCATTAGGAGTAGCACCCACCAAGGCAAAGAGAAGAGT GGTGCAGAGAGAAAAAA

GAGCAGTGGGAATAGGAGCTTTGTTCCTTGGGTTCTTGGGAGCAGCAGGAAGCACTA TGGGCGCAGCGTCAAT

GACGCTGACGGTACAGGCCAGACAATTATTGTCTGGTATAGTGCAGCAGCAGAACAA TTTGCTGAGGGCTATTG AGGCGCAACAGCATCTGTTGCAACTCACAGTCTGGGGCATCAAGCAGCTCCAGGCAAGAA TCCTGGCTGTGGA

AAGATACCTAAAGGATCAACAGCTCCTGGGGATTTGGGGTTGCTCTGGAAAACTCAT TTGCACCACTGCTGTGC

CTTGGAATGCTAGTTGGAGTAATAAATCTCTGGAACAGATTTGGAATCACACGACCT GGATGGAGTGGGACAGA

GAAATTAACAATTACACAAGCTTAATACACTCCTTAATTGAAGAATCGCAAAACCAG CAAGAAAAGAATGAACAAG

AATTATTGGAATTAGATAAATGGGCAAGTTTGTGGAATTGGTTTAACATAACAAATT GGCTGTGGTATATAAAATTA

TTCATAATGATAGTAGGAGGCTTGGTAGGTTTAAGAATAGTTTTTGCTGTACTTTCT ATAGTGAATAGAGTTAGGC

AGGGATATTCACCATTATCGTTTCAGACCCACCTCCCAACCCCGAGGGGACCCGACA GGCCCGAAGGAATAGAA

GAAGAAGGTGGAGAGAGAGACAGAGACAGATCCATTCGATTAGTGAACGGATCGGCA CTGCGTGCGCCAATTC

TGCAGACAAATGGCAGTATTCATCCACAATTTTAAAAGAAAAGGGGGGATTGGGGGG TACAGTGCAGGGGAAAG

AATAGTAGACATAATAGCAACAGACATACAAACTAAAGAATTACAAAAACAAATTAC AAAAATTCAAAATTTTCGGG

TTTATTACAGGGACAGCAGAGATCCAGTTTGGTTAGTACCGGGCCCTACGCGTTACT CGAGCCAAGGTCGGGCA

GGAAGAGGGCCTATTTCCCATGATTCCTTCATATTTGCATATACGATACAAGGCTGT TAGAGAGATAATTAGAATT

AATTTGACTGTAAACACAAAGATATTAGTACAAAATACGTGACGTAGAAAGTAATAA TTTCTTGGGTAGTTTGCAG

TTTTAAAATTATGTTTTAAAATGGACTATCATATGCTTACCGTAACTTGAAAGTATT TCGATTTCTTGGCTTTATATA

TCTTGTGGAAAGGACGAAACACCGAGCGAGCGCGAGTCCGCCGGTTTTAGAGCTAGA AATAGCAAGTTAAAATA

AGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTTTTTTTGGATC CAATTCTACCGGGTAGGG

GAGGCGCTTTTCCCAAGGCAGTCTGGAGCATGCGCTTTAGCAGCCCCGCTGGGCACT TGGCGCTACACAAGTG

GCCTCTGGCCTCGCACACATTCCACATCCACCGGTAGGCGCCAACCGGCTCCGTTCT TTGGTGGCCCCTTCGC

GCCACCTTCTACTCCTCCCCTAGTCAGGAAGTTCCCCCCCGCCCCGCAGCTCGCGTC GTGCAGGACGTGACAA

ATGGAAGTAGCACGTCTCACTAGTCTCGTGCAGATGGACAGCACCGCTGAGCAATGG AAGCGGGTAGGCCTTT

GGGGCAGCGGCCAATAGCAGCTTTGCTCCTTCGCTTTCTGGGCTCAGAGGCTGGGAA GGGGTGGGTCCGGGG

GCGGGCTCAGGGGCGGGCTCAGGGGCGGGGCGGGCGCCCGAAGGTCCTCCGGAGGCC CGGCATTCTGCAC

GCTTCAAAAGCGCACGTCTGCCGCGCTGTTCTCCTCTTCCTCATCTCCGGGCCTTTC GACCTGCATCCATCTAG

ATCTCGAGCAGCTGAAGCTTACCATGACCGAGTACAAGCCCACGGTGCGCCTCGCCA CCCGCGACGACGTCCC

CAGGGCCGTACGCACCCTCGCCGCCGCGTTCGCCGACTACCCCGCCACGCGCCACAC CGTCGATCCGGACCG

CCACATCGAGCGGGTCACCGAGCTGCAAGAACTCTTCCTCACGCGCGTCGGGCTCGA CATCGGCAAGGTGTGG

GTCGCGGACGACGGCGCCGCGGTGGCGGTCTGGACCACGCCGGAGAGCGTCGAAGCG GGGGCGGTGTTCGC

CGAGATCGGCCCGCGCATGGCCGAGTTGAGCGGTTCCCGGCTGGCCGCGCAGCAACA GATGGAAGGCCTCCT

GGCGCCGCACCGGCCCAAGGAGCCCGCGTGGTTCCTGGCCACCGTCGGCGTCTCGCC CGACCACCAGGGCA

AGGGTCTGGGCAGCGCCGTCGTGCTCCCCGGAGTGGAGGCGGCCGAGCGCGCCGGGG TGCCCGCCTTCCTG

GAGACCTCCGCGCCCCGCAACCTCCCCTTCTACGAGCGGCTCGGCTTCACCGTCACC GCCGACGTCGAGGTG

CCCGAAGGACCGCGCACCTGGTGCATGACCCGCAAGCCCGGTGCCGGCGGCGGGTCC GGAGGAGAGGGCAG

AGGAAGTCTCCTAACATGCGGTGACGTGGAGGAGAATCCTGGCCCAATGAGCGAGCT GATTAAGGAGAACATG

CACATGAAGCTGTACATGGAGGGCACCGTGGACAACCATCACTTCAAGTGCACATCC GAGGGCGAAGGCAAGC

CCTACGAGGGCACCCAGACCATGAGAATCAAGGTGGTCGAGGGCGGCCCTCTCCCCT TCGCCTTCGACATCCT

GGCTACTAGCTTCCTCTACGGCAGCAAGACCTTCATCAACCACACCCAGGGCATCCC CGACTTCTTCAAGCAGT

CCTTCCCTGAGGGCTTCACATGGGAGAGAGTCACCACATACGAGGACGGGGGCGTGC TGACCGCTACCCAGGA

CACCAGCCTCCAGGACGGCTGCCTCATCTACAACGTCAAGATCAGAGGGGTGAACTT CACATCCAACGGCCCT

GTGATGCAGAAGAAAACACTCGGCTGGGAGGCCTTCACCGAGACGCTGTACCCCGCT GACGGCGGCCTGGAA

GGCAGAAACGACATGGCCCTGAAGCTCGTGGGCGGGAGCCATCTGATCGCAAACATC AAGACCACATATAGAT

CCAAGAAACCCGCTAAGAACCTCAAGATGCCTGGCGTCTACTATGTGGACTACAGAC TGGAAAGAATCAAGGAG

GCCAACAACGAGACCTACGTCGAGCAGCACGAGGTGGCAGTGGCCAGATACTGCGAC CTCCCTAGCAAACTGG

GGCACAAGCTTAATTGAGCGGCCGCTAGGTACCTTTAAGACCAATGACTTACAAGGC AGCTGTAGATCTTAGCC

ACTTTTTAAAAGAAAAGGGGGGACTGGAAGGGCTAATTCACTCCCAAAGAAGTCAAG ATCTGCTTTTTGCCTGTA

CTGGGTCTCTCTGGTTAGACCAGAGTCTCTCTGGTTAGACCAGATCTGAGCCTGGGA GCTCTCTGGCTAACTAG

GGAACCCACTGCTTAAGCCTCAATAAAGCTTGCCTTGAGTGCTTCAAGTAGTGTGTG CCCGTCTGTTGTGTGACT

CTGGTAACTAGAGATCCCTCAGACCCTTTTAGTCAGTGTGGAAAATCTCTAGCAGTT TAAACCCGCTGATCAGCC

TCGACTGTGCCTTCTAGTTGCCAGCCATCTGTTGTTTGCCCCTCCCCCGTGCCTTCC TTGACCCTGGAAGGTGC

CACTCCCACTGTCCTTTCCTAATAAAATGAGGAAATTGCATCGCATTGTCTGAGTAG GTGTCATTCTATTCTGGG

GGGTGGGGTGGGGCAGGACAGCAAGGGGGAGGATTGGGAAGTCAATAGCAGGCATGC TGGGGATGCGGTGG

GCTCTATGGGCGGCCGTTAATTAAGCTTTTGTTCCCTTTAGTGAGGGTTAATTGCGC GCTTGGCGTAATCATGGT

CATAGCTGTTTCCTGTGTGAAATTGTTATCCGCTCACAATTCCACACAACATACGAG CCGGAAGCATAAAGTGTA

AAGCCTGGGGTGCCTAATGAGTGAGCTAACTCACATTAATTGCGTTGCGCTCACTGC CCGCTTTCCAGTCGGGA AACCTGTCGTGCCAGCTGCATTAATGAATCGGCCAACGCGCGGGGAGAGGCGGTTTGCGT ATTGGGCGCTCTT

CCGCTTCCTCGCTCACTGACTCGCTGCGCTCGGTCGTTCGGCTGCGGCGAGCGGTAT CAGCTCACTCAAAGGC

GGTAATACGGTTATCCACAGAATCAGGGGATAACGCAGGAAAGAACATGTGAGCAAA AGGCCAGCAAAAGGCCA

GGAACCGTAAAAAGGCCGCGTTGCTGGCGTTTTTCCATAGGCTCCGCCCCCCTGACG AGCATCACAAAAATCGA

CGCTCAAGTCAGAGGTGGCGAAACCCGACAGGACTATAAAGATACCAGGCGTTTCCC CCTGGAAGCTCCCTCG

TGCGCTCTCCTGTTCCGACCCTGCCGCTTACCGGATACCTGTCCGCCTTTCTCCCTT CGGGAAGCGTGGCGCTT

TCTCATAGCTCACGCTGTAGGTATCTCAGTTCGGTGTAGGTCGTTCGCTCCAAGCTG GGCTGTGTGCACGAACC

CCCCGTTCAGCCCGACCGCTGCGCCTTATCCGGTAACTATCGTCTTGAGTCCAACCC GGTAAGACACGACTTAT

CGCCACTGGCAGCAGCCACTGGTAACAGGATTAGCAGAGCGAGGTATGTAGGCGGTG CTACAGAGTTCTTGAA

GTGGTGGCCTAACTACGGCTACACTAGAAGGACAGTATTTGGTATCTGCGCTCTGCT GAAGCCAGTTACCTTCG

GAAAAAGAGTTGGTAGCTCTTGATCCGGCAAACAAACCACCGCTGGTAGCGGTGGTT TTTTTGTTTGCAAGCAG

CAGATTACGCGCAGAAAAAAAGGATCTCAAGAAGATCCTTTGATCTTTTCTACGGGG TCTGACGCTCAGTGGAAC

GAAAACTCACGTTAAGGGATTTTGGTCATGAGATTATCAAAAAGGATCTTCACCTAG ATCCTTTTAAATTAAAAAT

GAAGTTTTAAATCAATCTAAAGTATATATGAGTAAACTTGGTCTGACAGTTACCAAT GCTTAATCAGTGAGGCACC

TATCTCAGCGATCTGTCTATTTCGTTCATCCATAGTTGCCTGACTCCCCGTCGTGTA GATAACTACGATACGGGA

GGGCTTACCATCTGGCCCCAGTGCTGCAATGATACCGCGAGACCCACGCTCACCGGC TCCAGATTTATCAGCAA

TAAACCAGCCAGCCGGAAGGGCCGAGCGCAGAAGTGGTCCTGCAACTTTATCCGCCT CCATCCAGTCTATTAAT

TGTTGCCGGGAAGCTAGAGTAAGTAGTTCGCCAGTTAATAGTTTGCGCAACGTTGTT GCCATTGCTACAGGCATC

GTGGTGTCACGCTCGTCGTTTGGTATGGCTTCATTCAGCTCCGGTTCCCAACGATCA AGGCGAGTTACATGATC

CCCCATGTTGTGCAAAAAAGCGGTTAGCTCCTTCGGTCCTCCGATCGTTGTCAGAAG TAAGTTGGCCGCAGTGT

TATCACTCATGGTTATGGCAGCACTGCATAATTCTCTTACTGTCATGCCATCCGTAA GATGCTTTTCTGTGACTGG

TGAGTACTCAACCAAGTCATTCTGAGAATAGTGTATGCGGCGACCGAGTTGCTCTTG CCCGGCGTCAATACGGG

ATAATACCGCGCCACATAGCAGAACTTTAAAAGTGCTCATCATTGGAAAACGTTCTT CGGGGCGAAAACTCTCAA

GGATCTTACCGCTGTTGAGATCCAGTTCGATGTAACCCACTCGTGCACCCAACTGAT CTTCAGCATCTTTTACTTT

CACCAGCGTTTCTGGGTGAGCAAAAACAGGAAGGCAAAATGCCGCAAAAAAGGGAAT AAGGGCGACACGGAAA

TGTTGAATACTCATACTCTTCCTTTTTCAATATTATTGAAGCATTTATCAGGGTTAT TGTCTCATGAGCGGATACAT

ATTTGAATGTATTTAGAAAAATAAACAAATAGGGGTTCCGCGCACATTTCCCCGAAA AGTGCCAC pKLV-U6gRNA(Gabra5-sp sgRNA2) used in vitro for qPCT experiments (SEQ ID NO: 9)

CTAAATTGTAAGCGTTAATATTTTGTTAAAATTCGCGTTAAATTTTTGTTAAATCAG CTCATTTTTTAACCAATAGGC

CGAAATCGGCAAAATCCCTTATAAATCAAAAGAATAGACCGAGATAGGGTTGAGTGT TGTTCCAGTTTGGAACAA

GAGTCCACTATTAAAGAACGTGGACTCCAACGTCAAAGGGCGAAAAACCGTCTATCA GGGCGATGGCCCACTAC

GTGAACCATCACCCTAATCAAGTTTTTTGGGGTCGAGGTGCCGTAAAGCACTAAATC GGAACCCTAAAGGGAGC

CCCCGATTTAGAGCTTGACGGGGAAAGCCGGCGAACGTGGCGAGAAAGGAAGGGAAG AAAGCGAAAGGAGCG

GGCGCTAGGGCGCTGGCAAGTGTAGCGGTCACGCTGCGCGTAACCACCACACCCGCC GCGCTTAATGCGCCG

CTACAGGGCGCGTCCCATTCGCCATTCAGGCTGCGCAACTGTTGGGAAGGGCGATCG GTGCGGGCCTCTTCGC

TATTACGCCAGCTGGCGAAAGGGGGATGTGCTGCAAGGCGATTAAGTTGGGTAACGC CAGGGTTTTCCCAGTC

ACGACGTTGTAAAACGACGGCCAGTGAGCGCGCGTAATACGACTCACTATAGGGCGA ATTGACTAGTTATTAAT

AGTAATCAATTACGGGGTCATTAGTTCATAGCCCATATATGGAGTTCCGCGTTACAT AACTTACGGTAAATGGCC

CGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGACGTCAATAATGACGTATGTTC CCATAGTAACGCCAATA

GGGACTTTCCATTGACGTCAATGGGTGGAGTATTTACGGTAAACTGCCCACTTGGCA GTACATCAAGTGTATCAT

ATGCCAAGTACGCCCCCTATTGACGTCAATGACGGTAAATGGCCCGCCTGGCATTAT GCCCAGTACATGACCTT

ATGGGACTTTCCTACTTGGCAGTACATCTACGTATTAGTCATCGCTATTACCATGGT GATGCGGTTTTGGCAGTA

CATCAATGGGCGTGGATAGCGGTTTGACTCACGGGGATTTCCAAGTCTCCACCCCAT TGACGTCAATGGGAGTT

TGTTTTGGCACCAAAATCAACGGGACTTTCCAAAATGTCGTAACAACTCCGCCCCAT TGACGCAAATGGGCGGTA

GGCGTGTACGGTGGGAGGTCTATATAAGCAGCGCGTTTTGCCTGTACTGGGTCTCTC TGGTTAGACCAGATCTG

AGCCTGGGAGCTCTCTGGCTAACTAGGGAACCCACTGCTTAAGCCTCAATAAAGCTT GCCTTGAGTGCTTCAAG

TAGTGTGTGCCCGTCTGTTGTGTGACTCTGGTAACTAGAGATCCCTCAGACCCTTTT AGTCAGTGTGGAAAATCT

CTAGCAGTGGCGCCCGAACAGGGACTTGAAAGCGAAAGGGAAACCAGAGGAGCTCTC TCGACGCAGGACTCG

GCTTGCTGAAGCGCGCACGGCAAGAGGCGAGGGGCGGCGACTGGTGAGTACGCCAAA AATTTTGACTAGCGG

AGGCTAGAAGGAGAGAGATGGGTGCGAGAGCGTCAGTATTAAGCGGGGGAGAATTAG ATCGCGATGGGAAAAA

ATTCGGTTAAGGCCAGGGGGAAAGAAAAAATATAAATTAAAACATATAGTATGGGCA AGCAGGGAGCTAGAACG

ATTCGCAGTTAATCCTGGCCTGTTAGAAACATCAGAAGGCTGTAGACAAATACTGGG ACAGCTACAACCATCCCT TCAGACAGGATCAGAAGAACTTAGATCATTATATAATACAGTAGCAACCCTCTATTGTGT GCATCAAAGGATAGA

GATAAAAGACACCAAGGAAGCTTTAGACAAGATAGAGGAAGAGCAAAACAAAAGTAA GACCACCGCACAGCAAG

CGGCCGGCCGCGCTGATCTTCAGACCTGGAGGAGGAGATATGAGGGACAATTGGAGA AGTGAATTATATAAATA

TAAAGTAGTAAAAATTGAACCATTAGGAGTAGCACCCACCAAGGCAAAGAGAAGAGT GGTGCAGAGAGAAAAAA

GAGCAGTGGGAATAGGAGCTTTGTTCCTTGGGTTCTTGGGAGCAGCAGGAAGCACTA TGGGCGCAGCGTCAAT

GACGCTGACGGTACAGGCCAGACAATTATTGTCTGGTATAGTGCAGCAGCAGAACAA TTTGCTGAGGGCTATTG

AGGCGCAACAGCATCTGTTGCAACTCACAGTCTGGGGCATCAAGCAGCTCCAGGCAA GAATCCTGGCTGTGGA

AAGATACCTAAAGGATCAACAGCTCCTGGGGATTTGGGGTTGCTCTGGAAAACTCAT TTGCACCACTGCTGTGC

CTTGGAATGCTAGTTGGAGTAATAAATCTCTGGAACAGATTTGGAATCACACGACCT GGATGGAGTGGGACAGA

GAAATTAACAATTACACAAGCTTAATACACTCCTTAATTGAAGAATCGCAAAACCAG CAAGAAAAGAATGAACAAG

AATTATTGGAATTAGATAAATGGGCAAGTTTGTGGAATTGGTTTAACATAACAAATT GGCTGTGGTATATAAAATTA

TTCATAATGATAGTAGGAGGCTTGGTAGGTTTAAGAATAGTTTTTGCTGTACTTTCT ATAGTGAATAGAGTTAGGC

AGGGATATTCACCATTATCGTTTCAGACCCACCTCCCAACCCCGAGGGGACCCGACA GGCCCGAAGGAATAGAA

GAAGAAGGTGGAGAGAGAGACAGAGACAGATCCATTCGATTAGTGAACGGATCGGCA CTGCGTGCGCCAATTC

TGCAGACAAATGGCAGTATTCATCCACAATTTTAAAAGAAAAGGGGGGATTGGGGGG TACAGTGCAGGGGAAAG

AATAGTAGACATAATAGCAACAGACATACAAACTAAAGAATTACAAAAACAAATTAC AAAAATTCAAAATTTTCGGG

TTTATTACAGGGACAGCAGAGATCCAGTTTGGTTAGTACCGGGCCCTACGCGTTACT CGAGCCAAGGTCGGGCA

GGAAGAGGGCCTATTTCCCATGATTCCTTCATATTTGCATATACGATACAAGGCTGT TAGAGAGATAATTAGAATT

AATTTGACTGTAAACACAAAGATATTAGTACAAAATACGTGACGTAGAAAGTAATAA TTTCTTGGGTAGTTTGCAG

TTTTAAAATTATGTTTTAAAATGGACTATCATATGCTTACCGTAACTTGAAAGTATT TCGATTTCTTGGCTTTATATA

TCTTGTGGAAAGGACGAAAcaccGGTGACTAGCGATTATTCCAgtTTTAGAGCTAGA AATAGCAAGTTAAAATAAGG

CTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTTTTTTTGGATCCAA TTCTACCGGGTAGGGGAG

GCGCTTTTCCCAAGGCAGTCTGGAGCATGCGCTTTAGCAGCCCCGCTGGGCACTTGG CGCTACACAAGTGGCC

TCTGGCCTCGCACACATTCCACATCCACCGGTAGGCGCCAACCGGCTCCGTTCTTTG GTGGCCCCTTCGCGCC

ACCTTCTACTCCTCCCCTAGTCAGGAAGTTCCCCCCCGCCCCGCAGCTCGCGTCGTG CAGGACGTGACAAATG

GAAGTAGCACGTCTCACTAGTCTCGTGCAGATGGACAGCACCGCTGAGCAATGGAAG CGGGTAGGCCTTTGGG

GCAGCGGCCAATAGCAGCTTTGCTCCTTCGCTTTCTGGGCTCAGAGGCTGGGAAGGG GTGGGTCCGGGGGCG

GGCTCAGGGGCGGGCTCAGGGGCGGGGCGGGCGCCCGAAGGTCCTCCGGAGGCCCGG CATTCTGCACGCTT

CAAAAGCGCACGTCTGCCGCGCTGTTCTCCTCTTCCTCATCTCCGGGCCTTTCGACC TGCATCCATCTAGATCTC

GAGCAGCTGAAGCTTACCATGACCGAGTACAAGCCCACGGTGCGCCTCGCCACCCGC GACGACGTCCCCAGG

GCCGTACGCACCCTCGCCGCCGCGTTCGCCGACTACCCCGCCACGCGCCACACCGTC GATCCGGACCGCCAC

ATCGAGCGGGTCACCGAGCTGCAAGAACTCTTCCTCACGCGCGTCGGGCTCGACATC GGCAAGGTGTGGGTCG

CGGACGACGGCGCCGCGGTGGCGGTCTGGACCACGCCGGAGAGCGTCGAAGCGGGGG CGGTGTTCGCCGAG

ATCGGCCCGCGCATGGCCGAGTTGAGCGGTTCCCGGCTGGCCGCGCAGCAACAGATG GAAGGCCTCCTGGCG

CCGCACCGGCCCAAGGAGCCCGCGTGGTTCCTGGCCACCGTCGGCGTCTCGCCCGAC CACCAGGGCAAGGGT

CTGGGCAGCGCCGTCGTGCTCCCCGGAGTGGAGGCGGCCGAGCGCGCCGGGGTGCCC GCCTTCCTGGAGAC

CTCCGCGCCCCGCAACCTCCCCTTCTACGAGCGGCTCGGCTTCACCGTCACCGCCGA CGTCGAGGTGCCCGAA

GGACCGCGCACCTGGTGCATGACCCGCAAGCCCGGTGCCGGCGGCGGGTCCGGAGGA GAGGGCAGAGGAAG

TCTCCTAACATGCGGTGACGTGGAGGAGAATCCTGGCCCAATGAGCGAGCTGATTAA GGAGAACATGCACATGA

AGCTGTACATGGAGGGCACCGTGGACAACCATCACTTCAAGTGCACATCCGAGGGCG AAGGCAAGCCCTACGA

GGGCACCCAGACCATGAGAATCAAGGTGGTCGAGGGCGGCCCTCTCCCCTTCGCCTT CGACATCCTGGCTACT

AGCTTCCTCTACGGCAGCAAGACCTTCATCAACCACACCCAGGGCATCCCCGACTTC TTCAAGCAGTCCTTCCC

TGAGGGCTTCACATGGGAGAGAGTCACCACATACGAGGACGGGGGCGTGCTGACCGC TACCCAGGACACCAG

CCTCCAGGACGGCTGCCTCATCTACAACGTCAAGATCAGAGGGGTGAACTTCACATC CAACGGCCCTGTGATGC

AGAAGAAAACACTCGGCTGGGAGGCCTTCACCGAGACGCTGTACCCCGCTGACGGCG GCCTGGAAGGCAGAA

ACGACATGGCCCTGAAGCTCGTGGGCGGGAGCCATCTGATCGCAAACATCAAGACCA CATATAGATCCAAGAAA

CCCGCTAAGAACCTCAAGATGCCTGGCGTCTACTATGTGGACTACAGACTGGAAAGA ATCAAGGAGGCCAACAA

CGAGACCTACGTCGAGCAGCACGAGGTGGCAGTGGCCAGATACTGCGACCTCCCTAG CAAACTGGGGCACAAG

CTTAATTGAGCGGCCGCTAGGTACCTTTAAGACCAATGACTTACAAGGCAGCTGTAG ATCTTAGCCACTTTTTAA

AAGAAAAGGGGGGACTGGAAGGGCTAATTCACTCCCAAAGAAGTCAAGATCTGCTTT TTGCCTGTACTGGGTCT

CTCTGGTTAGACCAGAGTCTCTCTGGTTAGACCAGATCTGAGCCTGGGAGCTCTCTG GCTAACTAGGGAACCCA

CTGCTTAAGCCTCAATAAAGCTTGCCTTGAGTGCTTCAAGTAGTGTGTGCCCGTCTG TTGTGTGACTCTGGTAAC

TAGAGATCCCTCAGACCCTTTTAGTCAGTGTGGAAAATCTCTAGCAGTTTAAACCCG CTGATCAGCCTCGACTGT GCCTTCTAGTTGCCAGCCATCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGA AGGTGCCACTCCCA

CTGTCCTTTCCTAATAAAATGAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATT CTATTCTGGGGGGTGGGG

TGGGGCAGGACAGCAAGGGGGAGGATTGGGAAGTCAATAGCAGGCATGCTGGGGATG CGGTGGGCTCTATGG

GCGGCCGTTAATTAAGCTTTTGTTCCCTTTAGTGAGGGTTAATTGCGCGCTTGGCGT AATCATGGTCATAGCTGT

TTCCTGTGTGAAATTGTTATCCGCTCACAATTCCACACAACATACGAGCCGGAAGCA TAAAGTGTAAAGCCTGGG

GTGCCTAATGAGTGAGCTAACTCACATTAATTGCGTTGCGCTCACTGCCCGCTTTCC AGTCGGGAAACCTGTCG

TGCCAGCTGCATTAATGAATCGGCCAACGCGCGGGGAGAGGCGGTTTGCGTATTGGG CGCTCTTCCGCTTCCT

CGCTCACTGACTCGCTGCGCTCGGTCGTTCGGCTGCGGCGAGCGGTATCAGCTCACT CAAAGGCGGTAATACG

GTTATCCACAGAATCAGGGGATAACGCAGGAAAGAACATGTGAGCAAAAGGCCAGCA AAAGGCCAGGAACCGT

AAAAAGGCCGCGTTGCTGGCGTTTTTCCATAGGCTCCGCCCCCCTGACGAGCATCAC AAAAATCGACGCTCAAG

TCAGAGGTGGCGAAACCCGACAGGACTATAAAGATACCAGGCGTTTCCCCCTGGAAG CTCCCTCGTGCGCTCT

CCTGTTCCGACCCTGCCGCTTACCGGATACCTGTCCGCCTTTCTCCCTTCGGGAAGC GTGGCGCTTTCTCATAG

CTCACGCTGTAGGTATCTCAGTTCGGTGTAGGTCGTTCGCTCCAAGCTGGGCTGTGT GCACGAACCCCCCGTTC

AGCCCGACCGCTGCGCCTTATCCGGTAACTATCGTCTTGAGTCCAACCCGGTAAGAC ACGACTTATCGCCACTG

GCAGCAGCCACTGGTAACAGGATTAGCAGAGCGAGGTATGTAGGCGGTGCTACAGAG TTCTTGAAGTGGTGGC

CTAACTACGGCTACACTAGAAGGACAGTATTTGGTATCTGCGCTCTGCTGAAGCCAG TTACCTTCGGAAAAAGAG

TTGGTAGCTCTTGATCCGGCAAACAAACCACCGCTGGTAGCGGTGGTTTTTTTGTTT GCAAGCAGCAGATTACGC

GCAGAAAAAAAGGATCTCAAGAAGATCCTTTGATCTTTTCTACGGGGTCTGACGCTC AGTGGAACGAAAACTCAC

GTTAAGGGATTTTGGTCATGAGATTATCAAAAAGGATCTTCACCTAGATCCTTTTAA ATTAAAAATGAAGTTTTAAA

TCAATCTAAAGTATATATGAGTAAACTTGGTCTGACAGTTACCAATGCTTAATCAGT GAGGCACCTATCTCAGCGA

TCTGTCTATTTCGTTCATCCATAGTTGCCTGACTCCCCGTCGTGTAGATAACTACGA TACGGGAGGGCTTACCAT

CTGGCCCCAGTGCTGCAATGATACCGCGAGACCCACGCTCACCGGCTCCAGATTTAT CAGCAATAAACCAGCCA

GCCGGAAGGGCCGAGCGCAGAAGTGGTCCTGCAACTTTATCCGCCTCCATCCAGTCT ATTAATTGTTGCCGGGA

AGCTAGAGTAAGTAGTTCGCCAGTTAATAGTTTGCGCAACGTTGTTGCCATTGCTAC AGGCATCGTGGTGTCACG

CTCGTCGTTTGGTATGGCTTCATTCAGCTCCGGTTCCCAACGATCAAGGCGAGTTAC ATGATCCCCCATGTTGTG

CAAAAAAGCGGTTAGCTCCTTCGGTCCTCCGATCGTTGTCAGAAGTAAGTTGGCCGC AGTGTTATCACTCATGGT

TATGGCAGCACTGCATAATTCTCTTACTGTCATGCCATCCGTAAGATGCTTTTCTGT GACTGGTGAGTACTCAAC

CAAGTCATTCTGAGAATAGTGTATGCGGCGACCGAGTTGCTCTTGCCCGGCGTCAAT ACGGGATAATACCGCGC

CACATAGCAGAACTTTAAAAGTGCTCATCATTGGAAAACGTTCTTCGGGGCGAAAAC TCTCAAGGATCTTACCGC

TGTTGAGATCCAGTTCGATGTAACCCACTCGTGCACCCAACTGATCTTCAGCATCTT TTACTTTCACCAGCGTTTC

TGGGTGAGCAAAAACAGGAAGGCAAAATGCCGCAAAAAAGGGAATAAGGGCGACACG GAAATGTTGAATACTCA

TACTCTTCCTTTTTCAATATTATTGAAGCATTTATCAGGGTTATTGTCTCATGAGCG GATACATATTTGAATGTATT

TAGAAAAATAAACAAATAGGGGTTCCGCGCACATTTCCCCGAAAAGTGCCAC pKLV-U6gRNA(Gabra5-sp sgRNA3) used in vitro for qPCR experiments (SEQ ID NO: 10)

CTAAATTGTAAGCGTTAATATTTTGTTAAAATTCGCGTTAAATTTTTGTTAAATCAG CTCATTTTTTAACCAATAGGC

CGAAATCGGCAAAATCCCTTATAAATCAAAAGAATAGACCGAGATAGGGTTGAGTGT TGTTCCAGTTTGGAACAA

GAGTCCACTATTAAAGAACGTGGACTCCAACGTCAAAGGGCGAAAAACCGTCTATCA GGGCGATGGCCCACTAC

GTGAACCATCACCCTAATCAAGTTTTTTGGGGTCGAGGTGCCGTAAAGCACTAAATC GGAACCCTAAAGGGAGC

CCCCGATTTAGAGCTTGACGGGGAAAGCCGGCGAACGTGGCGAGAAAGGAAGGGAAG AAAGCGAAAGGAGCG

GGCGCTAGGGCGCTGGCAAGTGTAGCGGTCACGCTGCGCGTAACCACCACACCCGCC GCGCTTAATGCGCCG

CTACAGGGCGCGTCCCATTCGCCATTCAGGCTGCGCAACTGTTGGGAAGGGCGATCG GTGCGGGCCTCTTCGC

TATTACGCCAGCTGGCGAAAGGGGGATGTGCTGCAAGGCGATTAAGTTGGGTAACGC CAGGGTTTTCCCAGTC

ACGACGTTGTAAAACGACGGCCAGTGAGCGCGCGTAATACGACTCACTATAGGGCGA ATTGACTAGTTATTAAT

AGTAATCAATTACGGGGTCATTAGTTCATAGCCCATATATGGAGTTCCGCGTTACAT AACTTACGGTAAATGGCC

CGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGACGTCAATAATGACGTATGTTC CCATAGTAACGCCAATA

GGGACTTTCCATTGACGTCAATGGGTGGAGTATTTACGGTAAACTGCCCACTTGGCA GTACATCAAGTGTATCAT

ATGCCAAGTACGCCCCCTATTGACGTCAATGACGGTAAATGGCCCGCCTGGCATTAT GCCCAGTACATGACCTT

ATGGGACTTTCCTACTTGGCAGTACATCTACGTATTAGTCATCGCTATTACCATGGT GATGCGGTTTTGGCAGTA

CATCAATGGGCGTGGATAGCGGTTTGACTCACGGGGATTTCCAAGTCTCCACCCCAT TGACGTCAATGGGAGTT

TGTTTTGGCACCAAAATCAACGGGACTTTCCAAAATGTCGTAACAACTCCGCCCCAT TGACGCAAATGGGCGGTA

GGCGTGTACGGTGGGAGGTCTATATAAGCAGCGCGTTTTGCCTGTACTGGGTCTCTC TGGTTAGACCAGATCTG

AGCCTGGGAGCTCTCTGGCTAACTAGGGAACCCACTGCTTAAGCCTCAATAAAGCTT GCCTTGAGTGCTTCAAG TAGTGTGTGCCCGTCTGTTGTGTGACTCTGGTAACTAGAGATCCCTCAGACCCTTTTAGT CAGTGTGGAAAATCT

CTAGCAGTGGCGCCCGAACAGGGACTTGAAAGCGAAAGGGAAACCAGAGGAGCTCTC TCGACGCAGGACTCG

GCTTGCTGAAGCGCGCACGGCAAGAGGCGAGGGGCGGCGACTGGTGAGTACGCCAAA AATTTTGACTAGCGG

AGGCTAGAAGGAGAGAGATGGGTGCGAGAGCGTCAGTATTAAGCGGGGGAGAATTAG ATCGCGATGGGAAAAA

ATTCGGTTAAGGCCAGGGGGAAAGAAAAAATATAAATTAAAACATATAGTATGGGCA AGCAGGGAGCTAGAACG

ATTCGCAGTTAATCCTGGCCTGTTAGAAACATCAGAAGGCTGTAGACAAATACTGGG ACAGCTACAACCATCCCT

TCAGACAGGATCAGAAGAACTTAGATCATTATATAATACAGTAGCAACCCTCTATTG TGTGCATCAAAGGATAGA

GATAAAAGACACCAAGGAAGCTTTAGACAAGATAGAGGAAGAGCAAAACAAAAGTAA GACCACCGCACAGCAAG

CGGCCGGCCGCGCTGATCTTCAGACCTGGAGGAGGAGATATGAGGGACAATTGGAGA AGTGAATTATATAAATA

TAAAGTAGTAAAAATTGAACCATTAGGAGTAGCACCCACCAAGGCAAAGAGAAGAGT GGTGCAGAGAGAAAAAA

GAGCAGTGGGAATAGGAGCTTTGTTCCTTGGGTTCTTGGGAGCAGCAGGAAGCACTA TGGGCGCAGCGTCAAT

GACGCTGACGGTACAGGCCAGACAATTATTGTCTGGTATAGTGCAGCAGCAGAACAA TTTGCTGAGGGCTATTG

AGGCGCAACAGCATCTGTTGCAACTCACAGTCTGGGGCATCAAGCAGCTCCAGGCAA GAATCCTGGCTGTGGA

AAGATACCTAAAGGATCAACAGCTCCTGGGGATTTGGGGTTGCTCTGGAAAACTCAT TTGCACCACTGCTGTGC

CTTGGAATGCTAGTTGGAGTAATAAATCTCTGGAACAGATTTGGAATCACACGACCT GGATGGAGTGGGACAGA

GAAATTAACAATTACACAAGCTTAATACACTCCTTAATTGAAGAATCGCAAAACCAG CAAGAAAAGAATGAACAAG

AATTATTGGAATTAGATAAATGGGCAAGTTTGTGGAATTGGTTTAACATAACAAATT GGCTGTGGTATATAAAATTA

TTCATAATGATAGTAGGAGGCTTGGTAGGTTTAAGAATAGTTTTTGCTGTACTTTCT ATAGTGAATAGAGTTAGGC

AGGGATATTCACCATTATCGTTTCAGACCCACCTCCCAACCCCGAGGGGACCCGACA GGCCCGAAGGAATAGAA

GAAGAAGGTGGAGAGAGAGACAGAGACAGATCCATTCGATTAGTGAACGGATCGGCA CTGCGTGCGCCAATTC

TGCAGACAAATGGCAGTATTCATCCACAATTTTAAAAGAAAAGGGGGGATTGGGGGG TACAGTGCAGGGGAAAG

AATAGTAGACATAATAGCAACAGACATACAAACTAAAGAATTACAAAAACAAATTAC AAAAATTCAAAATTTTCGGG

TTTATTACAGGGACAGCAGAGATCCAGTTTGGTTAGTACCGGGCCCTACGCGTTACT CGAGCCAAGGTCGGGCA

GGAAGAGGGCCTATTTCCCATGATTCCTTCATATTTGCATATACGATACAAGGCTGT TAGAGAGATAATTAGAATT

AATTTGACTGTAAACACAAAGATATTAGTACAAAATACGTGACGTAGAAAGTAATAA TTTCTTGGGTAGTTTGCAG

TTTTAAAATTATGTTTTAAAATGGACTATCATATGCTTACCGTAACTTGAAAGTATT TCGATTTCTTGGCTTTATATA

TCTTGTGGAAAGGACGAAAcaccgAACATGGTCTTTCCCGAAGCgtTTTAGAGCTAG AAATAGCAAGTTAAAATAAG

GCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTTTTTTTGGATCCA ATTCTACCGGGTAGGGGA

GGCGCTTTTCCCAAGGCAGTCTGGAGCATGCGCTTTAGCAGCCCCGCTGGGCACTTG GCGCTACACAAGTGGC

CTCTGGCCTCGCACACATTCCACATCCACCGGTAGGCGCCAACCGGCTCCGTTCTTT GGTGGCCCCTTCGCGC

CACCTTCTACTCCTCCCCTAGTCAGGAAGTTCCCCCCCGCCCCGCAGCTCGCGTCGT GCAGGACGTGACAAAT

GGAAGTAGCACGTCTCACTAGTCTCGTGCAGATGGACAGCACCGCTGAGCAATGGAA GCGGGTAGGCCTTTGG

GGCAGCGGCCAATAGCAGCTTTGCTCCTTCGCTTTCTGGGCTCAGAGGCTGGGAAGG GGTGGGTCCGGGGGC

GGGCTCAGGGGCGGGCTCAGGGGCGGGGCGGGCGCCCGAAGGTCCTCCGGAGGCCCG GCATTCTGCACGCT

TCAAAAGCGCACGTCTGCCGCGCTGTTCTCCTCTTCCTCATCTCCGGGCCTTTCGAC CTGCATCCATCTAGATCT

CGAGCAGCTGAAGCTTACCATGACCGAGTACAAGCCCACGGTGCGCCTCGCCACCCG CGACGACGTCCCCAG

GGCCGTACGCACCCTCGCCGCCGCGTTCGCCGACTACCCCGCCACGCGCCACACCGT CGATCCGGACCGCCA

CATCGAGCGGGTCACCGAGCTGCAAGAACTCTTCCTCACGCGCGTCGGGCTCGACAT CGGCAAGGTGTGGGTC

GCGGACGACGGCGCCGCGGTGGCGGTCTGGACCACGCCGGAGAGCGTCGAAGCGGGG GCGGTGTTCGCCGA

GATCGGCCCGCGCATGGCCGAGTTGAGCGGTTCCCGGCTGGCCGCGCAGCAACAGAT GGAAGGCCTCCTGGC

GCCGCACCGGCCCAAGGAGCCCGCGTGGTTCCTGGCCACCGTCGGCGTCTCGCCCGA CCACCAGGGCAAGG

GTCTGGGCAGCGCCGTCGTGCTCCCCGGAGTGGAGGCGGCCGAGCGCGCCGGGGTGC CCGCCTTCCTGGAG

ACCTCCGCGCCCCGCAACCTCCCCTTCTACGAGCGGCTCGGCTTCACCGTCACCGCC GACGTCGAGGTGCCC

GAAGGACCGCGCACCTGGTGCATGACCCGCAAGCCCGGTGCCGGCGGCGGGTCCGGA GGAGAGGGCAGAGG

AAGTCTCCTAACATGCGGTGACGTGGAGGAGAATCCTGGCCCAATGAGCGAGCTGAT TAAGGAGAACATGCACA

TGAAGCTGTACATGGAGGGCACCGTGGACAACCATCACTTCAAGTGCACATCCGAGG GCGAAGGCAAGCCCTA

CGAGGGCACCCAGACCATGAGAATCAAGGTGGTCGAGGGCGGCCCTCTCCCCTTCGC CTTCGACATCCTGGCT

ACTAGCTTCCTCTACGGCAGCAAGACCTTCATCAACCACACCCAGGGCATCCCCGAC TTCTTCAAGCAGTCCTT

CCCTGAGGGCTTCACATGGGAGAGAGTCACCACATACGAGGACGGGGGCGTGCTGAC CGCTACCCAGGACAC

CAGCCTCCAGGACGGCTGCCTCATCTACAACGTCAAGATCAGAGGGGTGAACTTCAC ATCCAACGGCCCTGTGA

TGCAGAAGAAAACACTCGGCTGGGAGGCCTTCACCGAGACGCTGTACCCCGCTGACG GCGGCCTGGAAGGCA

GAAACGACATGGCCCTGAAGCTCGTGGGCGGGAGCCATCTGATCGCAAACATCAAGA CCACATATAGATCCAAG

AAACCCGCTAAGAACCTCAAGATGCCTGGCGTCTACTATGTGGACTACAGACTGGAA AGAATCAAGGAGGCCAA CAACGAGACCTACGTCGAGCAGCACGAGGTGGCAGTGGCCAGATACTGCGACCTCCCTAG CAAACTGGGGCAC

AAGCTTAATTGAGCGGCCGCTAGGTACCTTTAAGACCAATGACTTACAAGGCAGCTG TAGATCTTAGCCACTTTT

TAAAAGAAAAGGGGGGACTGGAAGGGCTAATTCACTCCCAAAGAAGTCAAGATCTGC TTTTTGCCTGTACTGGG

TCTCTCTGGTTAGACCAGAGTCTCTCTGGTTAGACCAGATCTGAGCCTGGGAGCTCT CTGGCTAACTAGGGAAC

CCACTGCTTAAGCCTCAATAAAGCTTGCCTTGAGTGCTTCAAGTAGTGTGTGCCCGT CTGTTGTGTGACTCTGGT

AACTAGAGATCCCTCAGACCCTTTTAGTCAGTGTGGAAAATCTCTAGCAGTTTAAAC CCGCTGATCAGCCTCGAC

TGTGCCTTCTAGTTGCCAGCCATCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGAC CCTGGAAGGTGCCACTC

CCACTGTCCTTTCCTAATAAAATGAGGAAATTGCATCGCATTGTCTGAGTAGGTGTC ATTCTATTCTGGGGGGTG

GGGTGGGGCAGGACAGCAAGGGGGAGGATTGGGAAGTCAATAGCAGGCATGCTGGGG ATGCGGTGGGCTCTA

TGGGCGGCCGTTAATTAAGCTTTTGTTCCCTTTAGTGAGGGTTAATTGCGCGCTTGG CGTAATCATGGTCATAGC

TGTTTCCTGTGTGAAATTGTTATCCGCTCACAATTCCACACAACATACGAGCCGGAA GCATAAAGTGTAAAGCCT

GGGGTGCCTAATGAGTGAGCTAACTCACATTAATTGCGTTGCGCTCACTGCCCGCTT TCCAGTCGGGAAACCTG

TCGTGCCAGCTGCATTAATGAATCGGCCAACGCGCGGGGAGAGGCGGTTTGCGTATT GGGCGCTCTTCCGCTT

CCTCGCTCACTGACTCGCTGCGCTCGGTCGTTCGGCTGCGGCGAGCGGTATCAGCTC ACTCAAAGGCGGTAAT

ACGGTTATCCACAGAATCAGGGGATAACGCAGGAAAGAACATGTGAGCAAAAGGCCA GCAAAAGGCCAGGAAC

CGTAAAAAGGCCGCGTTGCTGGCGTTTTTCCATAGGCTCCGCCCCCCTGACGAGCAT CACAAAAATCGACGCTC

AAGTCAGAGGTGGCGAAACCCGACAGGACTATAAAGATACCAGGCGTTTCCCCCTGG AAGCTCCCTCGTGCGC

TCTCCTGTTCCGACCCTGCCGCTTACCGGATACCTGTCCGCCTTTCTCCCTTCGGGA AGCGTGGCGCTTTCTCA

TAGCTCACGCTGTAGGTATCTCAGTTCGGTGTAGGTCGTTCGCTCCAAGCTGGGCTG TGTGCACGAACCCCCCG

TTCAGCCCGACCGCTGCGCCTTATCCGGTAACTATCGTCTTGAGTCCAACCCGGTAA GACACGACTTATCGCCA

CTGGCAGCAGCCACTGGTAACAGGATTAGCAGAGCGAGGTATGTAGGCGGTGCTACA GAGTTCTTGAAGTGGT

GGCCTAACTACGGCTACACTAGAAGGACAGTATTTGGTATCTGCGCTCTGCTGAAGC CAGTTACCTTCGGAAAA

AGAGTTGGTAGCTCTTGATCCGGCAAACAAACCACCGCTGGTAGCGGTGGTTTTTTT GTTTGCAAGCAGCAGATT

ACGCGCAGAAAAAAAGGATCTCAAGAAGATCCTTTGATCTTTTCTACGGGGTCTGAC GCTCAGTGGAACGAAAA

CTCACGTTAAGGGATTTTGGTCATGAGATTATCAAAAAGGATCTTCACCTAGATCCT TTTAAATTAAAAATGAAGTT

TTAAATCAATCTAAAGTATATATGAGTAAACTTGGTCTGACAGTTACCAATGCTTAA TCAGTGAGGCACCTATCTC

AGCGATCTGTCTATTTCGTTCATCCATAGTTGCCTGACTCCCCGTCGTGTAGATAAC TACGATACGGGAGGGCTT

ACCATCTGGCCCCAGTGCTGCAATGATACCGCGAGACCCACGCTCACCGGCTCCAGA TTTATCAGCAATAAACC

AGCCAGCCGGAAGGGCCGAGCGCAGAAGTGGTCCTGCAACTTTATCCGCCTCCATCC AGTCTATTAATTGTTGC

CGGGAAGCTAGAGTAAGTAGTTCGCCAGTTAATAGTTTGCGCAACGTTGTTGCCATT GCTACAGGCATCGTGGT

GTCACGCTCGTCGTTTGGTATGGCTTCATTCAGCTCCGGTTCCCAACGATCAAGGCG AGTTACATGATCCCCCA

TGTTGTGCAAAAAAGCGGTTAGCTCCTTCGGTCCTCCGATCGTTGTCAGAAGTAAGT TGGCCGCAGTGTTATCAC

TCATGGTTATGGCAGCACTGCATAATTCTCTTACTGTCATGCCATCCGTAAGATGCT TTTCTGTGACTGGTGAGTA

CTCAACCAAGTCATTCTGAGAATAGTGTATGCGGCGACCGAGTTGCTCTTGCCCGGC GTCAATACGGGATAATA

CCGCGCCACATAGCAGAACTTTAAAAGTGCTCATCATTGGAAAACGTTCTTCGGGGC GAAAACTCTCAAGGATCT

TACCGCTGTTGAGATCCAGTTCGATGTAACCCACTCGTGCACCCAACTGATCTTCAG CATCTTTTACTTTCACCA

GCGTTTCTGGGTGAGCAAAAACAGGAAGGCAAAATGCCGCAAAAAAGGGAATAAGGG CGACACGGAAATGTTG

AATACTCATACTCTTCCTTTTTCAATATTATTGAAGCATTTATCAGGGTTATTGTCT CATGAGCGGATACATATTTG

AATGTATTTAGAAAAATAAACAAATAGGGGTTCCGCGCACATTTCCCCGAAAAGTGC CAC pKLV-U6gRNA(Gabra5-sp sgRNALacZ) used as control in vitro for qPCR experiments (SEQ ID NO: 11)

CTAAATTGTAAGCGTTAATATTTTGTTAAAATTCGCGTTAAATTTTTGTTAAATCAG CTCATTTTTTAACCAATAGGC

CGAAATCGGCAAAATCCCTTATAAATCAAAAGAATAGACCGAGATAGGGTTGAGTGT TGTTCCAGTTTGGAACAA

GAGTCCACTATTAAAGAACGTGGACTCCAACGTCAAAGGGCGAAAAACCGTCTATCA GGGCGATGGCCCACTAC

GTGAACCATCACCCTAATCAAGTTTTTTGGGGTCGAGGTGCCGTAAAGCACTAAATC GGAACCCTAAAGGGAGC

CCCCGATTTAGAGCTTGACGGGGAAAGCCGGCGAACGTGGCGAGAAAGGAAGGGAAG AAAGCGAAAGGAGCG

GGCGCTAGGGCGCTGGCAAGTGTAGCGGTCACGCTGCGCGTAACCACCACACCCGCC GCGCTTAATGCGCCG

CTACAGGGCGCGTCCCATTCGCCATTCAGGCTGCGCAACTGTTGGGAAGGGCGATCG GTGCGGGCCTCTTCGC

TATTACGCCAGCTGGCGAAAGGGGGATGTGCTGCAAGGCGATTAAGTTGGGTAACGC CAGGGTTTTCCCAGTC

ACGACGTTGTAAAACGACGGCCAGTGAGCGCGCGTAATACGACTCACTATAGGGCGA ATTGACTAGTTATTAAT

AGTAATCAATTACGGGGTCATTAGTTCATAGCCCATATATGGAGTTCCGCGTTACAT AACTTACGGTAAATGGCC

CGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGACGTCAATAATGACGTATGTTC CCATAGTAACGCCAATA

GGGACTTTCCATTGACGTCAATGGGTGGAGTATTTACGGTAAACTGCCCACTTGGCA GTACATCAAGTGTATCAT ATGCCAAGTACGCCCCCTATTGACGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCC CAGTACATGACCTT

ATGGGACTTTCCTACTTGGCAGTACATCTACGTATTAGTCATCGCTATTACCATGGT GATGCGGTTTTGGCAGTA

CATCAATGGGCGTGGATAGCGGTTTGACTCACGGGGATTTCCAAGTCTCCACCCCAT TGACGTCAATGGGAGTT

TGTTTTGGCACCAAAATCAACGGGACTTTCCAAAATGTCGTAACAACTCCGCCCCAT TGACGCAAATGGGCGGTA

GGCGTGTACGGTGGGAGGTCTATATAAGCAGCGCGTTTTGCCTGTACTGGGTCTCTC TGGTTAGACCAGATCTG

AGCCTGGGAGCTCTCTGGCTAACTAGGGAACCCACTGCTTAAGCCTCAATAAAGCTT GCCTTGAGTGCTTCAAG

TAGTGTGTGCCCGTCTGTTGTGTGACTCTGGTAACTAGAGATCCCTCAGACCCTTTT AGTCAGTGTGGAAAATCT

CTAGCAGTGGCGCCCGAACAGGGACTTGAAAGCGAAAGGGAAACCAGAGGAGCTCTC TCGACGCAGGACTCG

GCTTGCTGAAGCGCGCACGGCAAGAGGCGAGGGGCGGCGACTGGTGAGTACGCCAAA AATTTTGACTAGCGG

AGGCTAGAAGGAGAGAGATGGGTGCGAGAGCGTCAGTATTAAGCGGGGGAGAATTAG ATCGCGATGGGAAAAA

ATTCGGTTAAGGCCAGGGGGAAAGAAAAAATATAAATTAAAACATATAGTATGGGCA AGCAGGGAGCTAGAACG

ATTCGCAGTTAATCCTGGCCTGTTAGAAACATCAGAAGGCTGTAGACAAATACTGGG ACAGCTACAACCATCCCT

TCAGACAGGATCAGAAGAACTTAGATCATTATATAATACAGTAGCAACCCTCTATTG TGTGCATCAAAGGATAGA

GATAAAAGACACCAAGGAAGCTTTAGACAAGATAGAGGAAGAGCAAAACAAAAGTAA GACCACCGCACAGCAAG

CGGCCGGCCGCGCTGATCTTCAGACCTGGAGGAGGAGATATGAGGGACAATTGGAGA AGTGAATTATATAAATA

TAAAGTAGTAAAAATTGAACCATTAGGAGTAGCACCCACCAAGGCAAAGAGAAGAGT GGTGCAGAGAGAAAAAA

GAGCAGTGGGAATAGGAGCTTTGTTCCTTGGGTTCTTGGGAGCAGCAGGAAGCACTA TGGGCGCAGCGTCAAT

GACGCTGACGGTACAGGCCAGACAATTATTGTCTGGTATAGTGCAGCAGCAGAACAA TTTGCTGAGGGCTATTG

AGGCGCAACAGCATCTGTTGCAACTCACAGTCTGGGGCATCAAGCAGCTCCAGGCAA GAATCCTGGCTGTGGA

AAGATACCTAAAGGATCAACAGCTCCTGGGGATTTGGGGTTGCTCTGGAAAACTCAT TTGCACCACTGCTGTGC

CTTGGAATGCTAGTTGGAGTAATAAATCTCTGGAACAGATTTGGAATCACACGACCT GGATGGAGTGGGACAGA

GAAATTAACAATTACACAAGCTTAATACACTCCTTAATTGAAGAATCGCAAAACCAG CAAGAAAAGAATGAACAAG

AATTATTGGAATTAGATAAATGGGCAAGTTTGTGGAATTGGTTTAACATAACAAATT GGCTGTGGTATATAAAATTA

TTCATAATGATAGTAGGAGGCTTGGTAGGTTTAAGAATAGTTTTTGCTGTACTTTCT ATAGTGAATAGAGTTAGGC

AGGGATATTCACCATTATCGTTTCAGACCCACCTCCCAACCCCGAGGGGACCCGACA GGCCCGAAGGAATAGAA

GAAGAAGGTGGAGAGAGAGACAGAGACAGATCCATTCGATTAGTGAACGGATCGGCA CTGCGTGCGCCAATTC

TGCAGACAAATGGCAGTATTCATCCACAATTTTAAAAGAAAAGGGGGGATTGGGGGG TACAGTGCAGGGGAAAG

AATAGTAGACATAATAGCAACAGACATACAAACTAAAGAATTACAAAAACAAATTAC AAAAATTCAAAATTTTCGGG

TTTATTACAGGGACAGCAGAGATCCAGTTTGGTTAGTACCGGGCCCTACGCGTTACT CGAGCCAAGGTCGGGCA

GGAAGAGGGCCTATTTCCCATGATTCCTTCATATTTGCATATACGATACAAGGCTGT TAGAGAGATAATTAGAATT

AATTTGACTGTAAACACAAAGATATTAGTACAAAATACGTGACGTAGAAAGTAATAA TTTCTTGGGTAGTTTGCAG

TTTTAAAATTATGTTTTAAAATGGACTATCATATGCTTACCGTAACTTGAAAGTATT TCGATTTCTTGGCTTTATATA

TCTTGTGGAAAGGACGAAAcaccgTGCGAATACGCCCACGCGATgtTTTAGAGCTAG AAATAGCAAGTTAAAATAAG

GCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTTTTTTTGGATCCA ATTCTACCGGGTAGGGGA

GGCGCTTTTCCCAAGGCAGTCTGGAGCATGCGCTTTAGCAGCCCCGCTGGGCACTTG GCGCTACACAAGTGGC

CTCTGGCCTCGCACACATTCCACATCCACCGGTAGGCGCCAACCGGCTCCGTTCTTT GGTGGCCCCTTCGCGC

CACCTTCTACTCCTCCCCTAGTCAGGAAGTTCCCCCCCGCCCCGCAGCTCGCGTCGT GCAGGACGTGACAAAT

GGAAGTAGCACGTCTCACTAGTCTCGTGCAGATGGACAGCACCGCTGAGCAATGGAA GCGGGTAGGCCTTTGG

GGCAGCGGCCAATAGCAGCTTTGCTCCTTCGCTTTCTGGGCTCAGAGGCTGGGAAGG GGTGGGTCCGGGGGC

GGGCTCAGGGGCGGGCTCAGGGGCGGGGCGGGCGCCCGAAGGTCCTCCGGAGGCCCG GCATTCTGCACGCT

TCAAAAGCGCACGTCTGCCGCGCTGTTCTCCTCTTCCTCATCTCCGGGCCTTTCGAC CTGCATCCATCTAGATCT

CGAGCAGCTGAAGCTTACCATGACCGAGTACAAGCCCACGGTGCGCCTCGCCACCCG CGACGACGTCCCCAG

GGCCGTACGCACCCTCGCCGCCGCGTTCGCCGACTACCCCGCCACGCGCCACACCGT CGATCCGGACCGCCA

CATCGAGCGGGTCACCGAGCTGCAAGAACTCTTCCTCACGCGCGTCGGGCTCGACAT CGGCAAGGTGTGGGTC

GCGGACGACGGCGCCGCGGTGGCGGTCTGGACCACGCCGGAGAGCGTCGAAGCGGGG GCGGTGTTCGCCGA

GATCGGCCCGCGCATGGCCGAGTTGAGCGGTTCCCGGCTGGCCGCGCAGCAACAGAT GGAAGGCCTCCTGGC

GCCGCACCGGCCCAAGGAGCCCGCGTGGTTCCTGGCCACCGTCGGCGTCTCGCCCGA CCACCAGGGCAAGG

GTCTGGGCAGCGCCGTCGTGCTCCCCGGAGTGGAGGCGGCCGAGCGCGCCGGGGTGC CCGCCTTCCTGGAG

ACCTCCGCGCCCCGCAACCTCCCCTTCTACGAGCGGCTCGGCTTCACCGTCACCGCC GACGTCGAGGTGCCC

GAAGGACCGCGCACCTGGTGCATGACCCGCAAGCCCGGTGCCGGCGGCGGGTCCGGA GGAGAGGGCAGAGG

AAGTCTCCTAACATGCGGTGACGTGGAGGAGAATCCTGGCCCAATGAGCGAGCTGAT TAAGGAGAACATGCACA

TGAAGCTGTACATGGAGGGCACCGTGGACAACCATCACTTCAAGTGCACATCCGAGG GCGAAGGCAAGCCCTA

CGAGGGCACCCAGACCATGAGAATCAAGGTGGTCGAGGGCGGCCCTCTCCCCTTCGC CTTCGACATCCTGGCT ACTAGCTTCCTCTACGGCAGCAAGACCTTCATCAACCACACCCAGGGCATCCCCGACTTC TTCAAGCAGTCCTT

CCCTGAGGGCTTCACATGGGAGAGAGTCACCACATACGAGGACGGGGGCGTGCTGAC CGCTACCCAGGACAC

CAGCCTCCAGGACGGCTGCCTCATCTACAACGTCAAGATCAGAGGGGTGAACTTCAC ATCCAACGGCCCTGTGA

TGCAGAAGAAAACACTCGGCTGGGAGGCCTTCACCGAGACGCTGTACCCCGCTGACG GCGGCCTGGAAGGCA

GAAACGACATGGCCCTGAAGCTCGTGGGCGGGAGCCATCTGATCGCAAACATCAAGA CCACATATAGATCCAAG

AAACCCGCTAAGAACCTCAAGATGCCTGGCGTCTACTATGTGGACTACAGACTGGAA AGAATCAAGGAGGCCAA

CAACGAGACCTACGTCGAGCAGCACGAGGTGGCAGTGGCCAGATACTGCGACCTCCC TAGCAAACTGGGGCAC

AAGCTTAATTGAGCGGCCGCTAGGTACCTTTAAGACCAATGACTTACAAGGCAGCTG TAGATCTTAGCCACTTTT

TAAAAGAAAAGGGGGGACTGGAAGGGCTAATTCACTCCCAAAGAAGTCAAGATCTGC TTTTTGCCTGTACTGGG

TCTCTCTGGTTAGACCAGAGTCTCTCTGGTTAGACCAGATCTGAGCCTGGGAGCTCT CTGGCTAACTAGGGAAC

CCACTGCTTAAGCCTCAATAAAGCTTGCCTTGAGTGCTTCAAGTAGTGTGTGCCCGT CTGTTGTGTGACTCTGGT

AACTAGAGATCCCTCAGACCCTTTTAGTCAGTGTGGAAAATCTCTAGCAGTTTAAAC CCGCTGATCAGCCTCGAC

TGTGCCTTCTAGTTGCCAGCCATCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGAC CCTGGAAGGTGCCACTC

CCACTGTCCTTTCCTAATAAAATGAGGAAATTGCATCGCATTGTCTGAGTAGGTGTC ATTCTATTCTGGGGGGTG

GGGTGGGGCAGGACAGCAAGGGGGAGGATTGGGAAGTCAATAGCAGGCATGCTGGGG ATGCGGTGGGCTCTA

TGGGCGGCCGTTAATTAAGCTTTTGTTCCCTTTAGTGAGGGTTAATTGCGCGCTTGG CGTAATCATGGTCATAGC

TGTTTCCTGTGTGAAATTGTTATCCGCTCACAATTCCACACAACATACGAGCCGGAA GCATAAAGTGTAAAGCCT

GGGGTGCCTAATGAGTGAGCTAACTCACATTAATTGCGTTGCGCTCACTGCCCGCTT TCCAGTCGGGAAACCTG

TCGTGCCAGCTGCATTAATGAATCGGCCAACGCGCGGGGAGAGGCGGTTTGCGTATT GGGCGCTCTTCCGCTT

CCTCGCTCACTGACTCGCTGCGCTCGGTCGTTCGGCTGCGGCGAGCGGTATCAGCTC ACTCAAAGGCGGTAAT

ACGGTTATCCACAGAATCAGGGGATAACGCAGGAAAGAACATGTGAGCAAAAGGCCA GCAAAAGGCCAGGAAC

CGTAAAAAGGCCGCGTTGCTGGCGTTTTTCCATAGGCTCCGCCCCCCTGACGAGCAT CACAAAAATCGACGCTC

AAGTCAGAGGTGGCGAAACCCGACAGGACTATAAAGATACCAGGCGTTTCCCCCTGG AAGCTCCCTCGTGCGC

TCTCCTGTTCCGACCCTGCCGCTTACCGGATACCTGTCCGCCTTTCTCCCTTCGGGA AGCGTGGCGCTTTCTCA

TAGCTCACGCTGTAGGTATCTCAGTTCGGTGTAGGTCGTTCGCTCCAAGCTGGGCTG TGTGCACGAACCCCCCG

TTCAGCCCGACCGCTGCGCCTTATCCGGTAACTATCGTCTTGAGTCCAACCCGGTAA GACACGACTTATCGCCA

CTGGCAGCAGCCACTGGTAACAGGATTAGCAGAGCGAGGTATGTAGGCGGTGCTACA GAGTTCTTGAAGTGGT

GGCCTAACTACGGCTACACTAGAAGGACAGTATTTGGTATCTGCGCTCTGCTGAAGC CAGTTACCTTCGGAAAA

AGAGTTGGTAGCTCTTGATCCGGCAAACAAACCACCGCTGGTAGCGGTGGTTTTTTT GTTTGCAAGCAGCAGATT

ACGCGCAGAAAAAAAGGATCTCAAGAAGATCCTTTGATCTTTTCTACGGGGTCTGAC GCTCAGTGGAACGAAAA

CTCACGTTAAGGGATTTTGGTCATGAGATTATCAAAAAGGATCTTCACCTAGATCCT TTTAAATTAAAAATGAAGTT

TTAAATCAATCTAAAGTATATATGAGTAAACTTGGTCTGACAGTTACCAATGCTTAA TCAGTGAGGCACCTATCTC

AGCGATCTGTCTATTTCGTTCATCCATAGTTGCCTGACTCCCCGTCGTGTAGATAAC TACGATACGGGAGGGCTT

ACCATCTGGCCCCAGTGCTGCAATGATACCGCGAGACCCACGCTCACCGGCTCCAGA TTTATCAGCAATAAACC

AGCCAGCCGGAAGGGCCGAGCGCAGAAGTGGTCCTGCAACTTTATCCGCCTCCATCC AGTCTATTAATTGTTGC

CGGGAAGCTAGAGTAAGTAGTTCGCCAGTTAATAGTTTGCGCAACGTTGTTGCCATT GCTACAGGCATCGTGGT

GTCACGCTCGTCGTTTGGTATGGCTTCATTCAGCTCCGGTTCCCAACGATCAAGGCG AGTTACATGATCCCCCA

TGTTGTGCAAAAAAGCGGTTAGCTCCTTCGGTCCTCCGATCGTTGTCAGAAGTAAGT TGGCCGCAGTGTTATCAC

TCATGGTTATGGCAGCACTGCATAATTCTCTTACTGTCATGCCATCCGTAAGATGCT TTTCTGTGACTGGTGAGTA

CTCAACCAAGTCATTCTGAGAATAGTGTATGCGGCGACCGAGTTGCTCTTGCCCGGC GTCAATACGGGATAATA

CCGCGCCACATAGCAGAACTTTAAAAGTGCTCATCATTGGAAAACGTTCTTCGGGGC GAAAACTCTCAAGGATCT

TACCGCTGTTGAGATCCAGTTCGATGTAACCCACTCGTGCACCCAACTGATCTTCAG CATCTTTTACTTTCACCA

GCGTTTCTGGGTGAGCAAAAACAGGAAGGCAAAATGCCGCAAAAAAGGGAATAAGGG CGACACGGAAATGTTG

AATACTCATACTCTTCCTTTTTCAATATTATTGAAGCATTTATCAGGGTTATTGTCT CATGAGCGGATACATATTTG

AATGTATTTAGAAAAATAAACAAATAGGGGTTCCGCGCACATTTCCCCGAAAAGTGC CAC pLenti-eF1a dCAS-VP64 Blast for in vitro for qPCR experiments (SEQ ID NO: 12)

GTCGACGGATCGGGAGATCTCCCGATCCCCTATGGTGCACTCTCAGTACAATCTGCT CTGATGCCGCATAGTTA

AGCCAGTATCTGCTCCCTGCTTGTGTGTTGGAGGTCGCTGAGTAGTGCGCGAGCAAA ATTTAAGCTACAACAAG

GCAAGGCTTGACCGACAATTGCATGAAGAATCTGCTTAGGGTTAGGCGTTTTGCGCT GCTTCGCGATGTACGGG

CCAGATATACGCGTTGACATTGATTATTGACTAGTTATTAATAGTAATCAATTACGG GGTCATTAGTTCATAGCCC

ATATATGGAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCC CAACGACCCCCGCCCAT

TGACGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGAC GTCAATGGGTGGAGTATT TACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTA TTGACGTCAATGACG

GTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT GGCAGTACATCTACGTAT

TAGTCATCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAATGGGCGTGGAT AGCGGTTTGACTCACGG

GGATTTCCAAGTCTCCACCCCATTGACGTCAATGGGAGTTTGTTTTGGCACCAAAAT CAACGGGACTTTCCAAAA

TGTCGTAACAACTCCGCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAG GTCTATATAAGCAGCG

CGTTTTGCCTGTACTGGGTCTCTCTGGTTAGACCAGATCTGAGCCTGGGAGCTCTCT GGCTAACTAGGGAACCC

ACTGCTTAAGCCTCAATAAAGCTTGCCTTGAGTGCTTCAAGTAGTGTGTGCCCGTCT GTTGTGTGACTCTGGTAA

CTAGAGATCCCTCAGACCCTTTTAGTCAGTGTGGAAAATCTCTAGCAGTGGCGCCCG AACAGGGACTTGAAAGC

GAAAGGGAAACCAGAGGAGCTCTCTCGACGCAGGACTCGGCTTGCTGAAGCGCGCAC GGCAAGAGGCGAGGG

GCGGCGACTGGTGAGTACGCCAAAAATTTTGACTAGCGGAGGCTAGAAGGAGAGAGA TGGGTGCGAGAGCGTC

AGTATTAAGCGGGGGAGAATTAGATCGCGATGGGAAAAAATTCGGTTAAGGCCAGGG GGAAAGAAAAAATATAA

ATTAAAACATATAGTATGGGCAAGCAGGGAGCTAGAACGATTCGCAGTTAATCCTGG CCTGTTAGAAACATCAGA

AGGCTGTAGACAAATACTGGGACAGCTACAACCATCCCTTCAGACAGGATCAGAAGA ACTTAGATCATTATATAA

TACAGTAGCAACCCTCTATTGTGTGCATCAAAGGATAGAGATAAAAGACACCAAGGA AGCTTTAGACAAGATAGA

GGAAGAGCAAAACAAAAGTAAGACCACCGCACAGCAAGCGGCCGCTGATCTTCAGAC CTGGAGGAGGAGATAT

GAGGGACAATTGGAGAAGTGAATTATATAAATATAAAGTAGTAAAAATTGAACCATT AGGAGTAGCACCCACCAA

GGCAAAGAGAAGAGTGGTGCAGAGAGAAAAAAGAGCAGTGGGAATAGGAGCTTTGTT CCTTGGGTTCTTGGGA

GCAGCAGGAAGCACTATGGGCGCAGCGTCAATGACGCTGACGGTACAGGCCAGACAA TTATTGTCTGGTATAGT

GCAGCAGCAGAACAATTTGCTGAGGGCTATTGAGGCGCAACAGCATCTGTTGCAACT CACAGTCTGGGGCATCA

AGCAGCTCCAGGCAAGAATCCTGGCTGTGGAAAGATACCTAAAGGATCAACAGCTCC TGGGGATTTGGGGTTGC

TCTGGAAAACTCATTTGCACCACTGCTGTGCCTTGGAATGCTAGTTGGAGTAATAAA TCTCTGGAACAGATTTGG

AATCACACGACCTGGATGGAGTGGGACAGAGAAATTAACAATTACACAAGCTTAATA CACTCCTTAATTGAAGAA

TCGCAAAACCAGCAAGAAAAGAATGAACAAGAATTATTGGAATTAGATAAATGGGCA AGTTTGTGGAATTGGTTT

AACATAACAAATTGGCTGTGGTATATAAAATTATTCATAATGATAGTAGGAGGCTTG GTAGGTTTAAGAATAGTTT

TTGCTGTACTTTCTATAGTGAATAGAGTTAGGCAGGGATATTCACCATTATCGTTTC AGACCCACCTCCCAACCC

CGAGGGGACCCGACAGGCCCGAAGGAATAGAAGAAGAAGGTGGAGAGAGAGACAGAG ACAGATCCATTCGATT

AGTGAACGGATCGGCACTGCGTGCGCCAATTCTGCAGACAAATGGCAGTATTCATCC ACAATTTTAAAAGAAAAG

GGGGGATTGGGGGGTACAGTGCAGGGGAAAGAATAGTAGACATAATAGCAACAGACA TACAAACTAAAGAATTA

CAAAAACAAATTACAAAAATTCAAAATTTTCGGGTTTATTACAGGGACAGCAGAGAT CCAGTTTGGTTAATTAGCT

AGCTGCAAAGATGGATAAAGTTTTAAACAGAGAGGAATCTTTGCAGCTAATGGACCT TCTAGGTCTTGAAAGGAG

TGGGAATTGGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCACAGTCCCCG AGAAGTTGGGGGGAG

GGGTCGGCAATTGAACCGGTGCCTAGAGAAGGTGGCGCGGGGTAAACTGGGAAAGTG ATGTCGTGTACTGGCT

CCGCCTTTTTCCCGAGGGTGGGGGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAA CGTTCTTTTTCGCAACG

GGTTTGCCGCCAGAACACAGGTAAGTGCCGTGTGTGGTTCCCGCGGGCCTGGCCTCT TTACGGGTTATGGCCC

TTGCGTGCCTTGAATTACTTCCACCTGGCTGCAGTACGTGATTCTTGATCCCGAGCT TCGGGTTGGAAGTGGGT

GGGAGAGTTCGAGGCCTTGCGCTTAAGGAGCCCCTTCGCCTCGTGCTTGAGTTGAGG CCTGGCCTGGGCGCTG

GGGCCGCCGCGTGCGAATCTGGTGGCACCTTCGCGCCTGTCTCGCTGCTTTCGATAA GTCTCTAGCCATTTAAA

ATTTTTGATGACCTGCTGCGACGCTTTTTTTCTGGCAAGATAGTCTTGTAAATGCGG GCCAAGATCTGCACACTG

GTATTTCGGTTTTTGGGGCCGCGGGCGGCGACGGGGCCCGTGCGTCCCAGCGCACAT GTTCGGCGAGGCGGG

GCCTGCGAGCGCGGCCACCGAGAATCGGACGGGGGTAGTCTCAAGCTGGCCGGCCTG CTCTGGTGCCTGGCC

TCGCGCCGCCGTGTATCGCCCCGCCCTGGGCGGCAAGGCTGGCCCGGTCGGCACCAG TTGCGTGAGCGGAAA

GATGGCCGCTTCCCGGCCCTGCTGCAGGGAGCTCAAAATGGAGGACGCGGCGCTCGG GAGAGCGGGCGGGT

GAGTCACCCACACAAAGGAAAAGGGCCTTTCCGTCCTCAGCCGTCGCTTCATGTGAC TCCACGGAGTACCGGG

CGCCGTCCAGGCACCTCGATTAGTTCTCGAGCTTTTGGAGTACGTCGTCTTTAGGTT GGGGGGAGGGGTTTTAT

GCGATGGAGTTTCCCCACACTGAGTGGGTGGAGACTGAAGTTAGGCCAGCTTGGCAC TTGATGTAATTCTCCTT

GGAATTTGCCCTTTTTGAGTTTGGATCTTGGTTCATTCTCAAGCCTCAGACAGTGGT TCAAAGTTTTTTTCTTCCA

TTTCAGGTGTCGTGACGTACGGCCACCATGAAAAGGCCGGCGGCCACGAAAAAGGCC GGCCAGGCAAAAAAGA

AAAAGGACAAGAAGTACAGCATCGGCCTGGCCATCGGCACCAACTCTGTGGGCTGGG CCGTGATCACCGACGA

GTACAAGGTGCCCAGCAAGAAATTCAAGGTGCTGGGCAACACCGACCGGCACAGCAT CAAGAAGAACCTGATC

GGAGCCCTGCTGTTCGACAGCGGCGAAACAGCCGAGGCCACCCGGCTGAAGAGAACC GCCAGAAGAAGATAC

ACCAGACGGAAGAACCGGATCTGCTATCTGCAAGAGATCTTCAGCAACGAGATGGCC AAGGTGGACGACAGCT

TCTTCCACAGACTGGAAGAGTCCTTCCTGGTGGAAGAGGATAAGAAGCACGAGCGGC ACCCCATCTTCGGCAA

CATCGTGGACGAGGTGGCCTACCACGAGAAGTACCCCACCATCTACCACCTGAGAAA GAAACTGGTGGACAGC ACCGACAAGGCCGACCTGCGGCTGATCTATCTGGCCCTGGCCCACATGATCAAGTTCCGG GGCCACTTCCTGA

TCGAGGGCGACCTGAACCCCGACAACAGCGACGTGGACAAGCTGTTCATCCAGCTGG TGCAGACCTACAACCA

GCTGTTCGAGGAAAACCCCATCAACGCCAGCGGCGTGGACGCCAAGGCCATCCTGTC TGCCAGACTGAGCAAG

AGCAGACGGCTGGAAAATCTGATCGCCCAGCTGCCCGGCGAGAAGAAGAATGGCCTG TTCGGCAACCTGATTG

CCCTGAGCCTGGGCCTGACCCCCAACTTCAAGAGCAACTTCGACCTGGCCGAGGATG CCAAACTGCAGCTGAG

CAAGGACACCTACGACGACGACCTGGACAACCTGCTGGCCCAGATCGGCGACCAGTA CGCCGACCTGTTTCTG

GCCGCCAAGAACCTGTCCGACGCCATCCTGCTGAGCGACATCCTGAGAGTGAACACC GAGATCACCAAGGCCC

CCCTGAGCGCCTCTATGATCAAGAGATACGACGAGCACCACCAGGACCTGACCCTGC TGAAAGCTCTCGTGCG

GCAGCAGCTGCCTGAGAAGTACAAAGAGATTTTCTTCGACCAGAGCAAGAACGGCTA CGCCGGCTACATTGACG

GCGGAGCCAGCCAGGAAGAGTTCTACAAGTTCATCAAGCCCATCCTGGAAAAGATGG ACGGCACCGAGGAACT

GCTCGTGAAGCTGAACAGAGAGGACCTGCTGCGGAAGCAGCGGACCTTCGACAACGG CAGCATCCCCCACCA

GATCCACCTGGGAGAGCTGCACGCCATTCTGCGGCGGCAGGAAGATTTTTACCCATT CCTGAAGGACAACCGG

GAAAAGATCGAGAAGATCCTGACCTTCCGCATCCCCTACTACGTGGGCCCTCTGGCC AGGGGAAACAGCAGATT

CGCCTGGATGACCAGAAAGAGCGAGGAAACCATCACCCCCTGGAACTTCGAGGAAGT GGTGGACAAGGGCGCT

TCCGCCCAGAGCTTCATCGAGCGGATGACCAACTTCGATAAGAACCTGCCCAACGAG AAGGTGCTGCCCAAGC

ACAGCCTGCTGTACGAGTACTTCACCGTGTATAACGAGCTGACCAAAGTGAAATACG TGACCGAGGGAATGAGA

AAGCCCGCCTTCCTGAGCGGCGAGCAGAAAAAGGCCATCGTGGACCTGCTGTTCAAG ACCAACCGGAAATGAC

CGTGAAGCAGCTGAAAGAGGACTACTTCAAGAAAATCGAGTGCTTCGACTCCGTGGA AATCTCCGGCGTGGAAG

ATCGGTTCAACGCCTCCCTGGGCACATACCACGATCTGCTGAAAATTATCAAGGACA AGGACTTCCTGGACAAT

GAGGAAAACGAGGACATTCTGGAAGATATCGTGCTGACCCTGACACTGTTTGAGGAC AGAGAGATGATCGAGGA

ACGGCTGAAAACCTATGCCCACCTGTTCGACGACAAAGTGATGAAGCAGCTGAAGCG GCGGAGATACACCGGC

TGGGGCAGGCTGAGCCGGAAGCTGATCAACGGCATCCGGGACAAGCAGTCCGGCAAG ACAATCCTGGATTTCC

TGAAGTCCGACGGCTTCGCCAACAGAAACTTCATGCAGCTGATCCACGACGACAGCC TGACCTTTAAAGAGGAC

ATCCAGAAAGCCCAGGTGTCCGGCCAGGGCGATAGCCTGCACGAGCACATTGCCAAT CTGGCCGGCAGCCCC

GCCATTAAGAAGGGCATCCTGCAGACAGTGAAGGTGGTGGACGAGCTCGTGAAAGTG ATGGGCCGGCACAAGC

CCGAGAACATCGTGATCGAAATGGCCAGAGAGAACCAGACCACCCAGAAGGGACAGA AGAACAGCCGCGAGAG

AATGAAGCGGATCGAAGAGGGCATCAAAGAGCTGGGCAGCCAGATCCTGAAAGAACA CCCCGTGGAAAACACC

CAGCTGCAGAACGAGAAGCTGTACCTGTACTACCTGCAGAATGGGCGGGATATGTAC GTGGACCAGGAACTGG

ACATCAACCGGCTGTCCGACTACGATGTGGACCACATCGTGCCTCAGAGCTTTCTGA AGGACGACTCCATCGAC

AACAAGGTGCTGACCAGAAGCGACAAGGCCCGGGGCAAGAGCGACAACGTGCCCTCC GAAGAGGTCGTGAAG

AAGATGAAGAACTACTGGCGGCAGCTGCTGAACGCCAAGCTGATTACCCAGAGAAAG TTCGACAATCTGACCAA

GGCCGAGAGAGGCGGCCTGAGCGAACTGGATAAGGCCGGCTTCATCAAGAGACAGCT GGTGGAAACCCGGCA

GATCACAAAGCACGTGGCACAGATCCTGGACTCCCGGATGAACACTAAGTACGACGA GAATGACAAGCTGATCC

GGGAAGTGAAAGTGATCACCCTGAAGTCCAAGCTGGTGTCCGATTTCCGGAAGGATT TCCAGTTTTACAAAGTG

CGCGAGATCAACAACTACCACCACGCCCACGACGCCTACCTGAACGCCGTCGTGGGA ACCGCCCTGATCAAAA

AGTACCCTAAGCTGGAAAGCGAGTTCGTGTACGGCGACTACAAGGTGTACGACGTGC GGAAGATGATCGCCAA

GAGCGAGCAGGAAATCGGCAAGGCTACCGCCAAGTACTTCTTCTACAGCAACATCAT GAACTTTTTCAAGACCG

AGATTACCCTGGCCAACGGCGAGATCCGGAAGCGGCCTCTGATCGAGACAAACGGCG AAACCGGGGAGATCGT

GTGGGATAAGGGCCGGGATTTTGCCACCGTGCGGAAAGTGCTGAGCATGCCCCAAGT GAATATCGTGAAAAAG

ACCGAGGTGCAGACAGGCGGCTTCAGCAAAGAGTCTATCCTGCCCAAGAGGAACAGC GATAAGCTGATCGCCA

GAAAGAAGGACTGGGACCCTAAGAAGTACGGCGGCTTCGACAGCCCCACCGTGGCCT ATTCTGTGCTGGTGGT

GGCCAAAGTGGAAAAGGGCAAGTCCAAGAAACTGAAGAGTGTGAAAGAGCTGCTGGG GATCACCATCATGGAA

AGAAGCAGCTTCGAGAAGAATCCCATCGACTTTCTGGAAGCCAAGGGCTACAAAGAA GTGAAAAAGGACCTGAT

CATCAAGCTGCCTAAGTACTCCCTGTTCGAGCTGGAAAACGGCCGGAAGAGAATGCT GGCCTCTGCCGGCGAA

CTGCAGAAGGGAAACGAACTGGCCCTGCCCTCCAAATATGTGAACTTCCTGTACCTG GCCAGCCACTATGAGAA

GCTGAAGGGCTCCCCCGAGGATAATGAGCAGAAACAGCTGTTTGTGGAACAGCACAA GCACTACCTGGACGAG

ATCATCGAGCAGATCAGCGAGTTCTCCAAGAGAGTGATCCTGGCCGACGCTAATCTG GACAAAGTGCTGTCCGC

CTACAACAAGCACCGGGATAAGCCCATCAGAGAGCAGGCCGAGAATATCATCCACCT GTTTACCCTGACCAATC

TGGGAGCCCCTGCCGCCTTCAAGTACTTTGACACCACCATCGACCGGAAGAGGTACA CCAGCACCAAAGAGGT

GCTGGACGCCACCCTGATCCACCAGAGCATCACCGGCCTGTACGAGACACGGATCGA CCTGTCTCAGCTGGGA

GGCGACAGCGCTGGAGGAGGTGGAAGCGGAGGAGGAGGAAGCGGAGGAGGAGGTAGC GGACCTAAGAAAAA

GAGGAAGGTGGCGGCCGCTGGATCCGGACGGGCTGACGCATTGGACGATTTTGATCT GGATATGCTGGGAAGT

GACGCCCTCGATGATTTTGACCTTGACATGCTTGGTTCGGATGCCCTTGATGACTTT GACCTCGACATGCTCGG CAGTGACGCCCTTGATGATTTCGACCTGGACATGCTGATTAACTGTACAGGCAGTGGAGA GGGCAGAGGAAGTC

TGCTAACATGCGGTGACGTCGAGGAGAATCCTGGCCCAATGGCCAAGCCTTTGTCTC AAGAAGAATCCACCCTC

ATTGAAAGAGCAACGGCTACAATCAACAGCATCCCCATCTCTGAAGACTACAGCGTC GCCAGCGCAGCTCTCTC

TAGCGACGGCCGCATCTTCACTGGTGTCAATGTATATCATTTTACTGGGGGACCTTG TGCAGAACTCGTGGTGC

TGGGCACTGCTGCTGCTGCGGCAGCTGGCAACCTGACTTGTATCGTCGCGATCGGAA ATGAGAACAGGGGCAT

CTTGAGCCCCTGCGGACGGTGCCGACAGGTGCTTCTCGATCTGCATCCTGGGATCAA AGCCATAGTGAAGGAC

AGTGATGGACAGCCGACGGCAGTTGGGATTCGTGAATTGCTGCCCTCTGGTTATGTG TGGGAGGGCTAAGAATT

CGATATCAAGCTTATCGGTAATCAACCTCTGGATTACAAAATTTGTGAAAGATTGAC TGGTATTCTTAACTATGTT

GCTCCTTTTACGCTATGTGGATACGCTGCTTTAATGCCTTTGTATCATGCTATTGCT TCCCGTATGGCTTTCATTT

TCTCCTCCTTGTATAAATCCTGGTTGCTGTCTCTTTATGAGGAGTTGTGGCCCGTTG TCAGGCAACGTGGCGTGG

TGTGCACTGTGTTTGCTGACGCAACCCCCACTGGTTGGGGCATTGCCACCACCTGTC AGCTCCTTTCCGGGACT

TTCGCTTTCCCCCTCCCTATTGCCACGGCGGAACTCATCGCCGCCTGCCTTGCCCGC TGCTGGACAGGGGCTC

GGCTGTTGGGCACTGACAATTCCGTGGTGTTGTCGGGGAAATCATCGTCCTTTCCTT GGCTGCTCGCCTGTGTT

GCCACCTGGATTCTGCGCGGGACGTCCTTCTGCTACGTCCCTTCGGCCCTCAATCCA GCGGACCTTCCTTCCCG

CGGCCTGCTGCCGGCTCTGCGGCCTCTTCCGCGTCTTCGCCTTCGCCCTCAGACGAG TCGGATCTCCCTTTGG

GCCGCCTCCCCGCATCGATACCGTCGACCTCGAGACCTAGAAAAACATGGAGCAATC ACAAGTAGCAATACAGC

AGCTACCAATGCTGATTGTGCCTGGCTAGAAGCACAAGAGGAGGAGGAGGTGGGTTT TCCAGTCACACCTCAG

GTACCTTTAAGACCAATGACTTACAAGGCAGCTGTAGATCTTAGCCACTTTTTAAAA GAAAAGGGGGGACTGGAA

GGGCTAATTCACTCCCAACGAAGACAAGATATCCTTGATCTGTGGATCTACCACACA CAAGGCTACTTCCCTGAT

TGGCAGAACTACACACCAGGGCCAGGGATCAGATATCCACTGACCTTTGGATGGTGC TACAAGCTAGTACCAGT

TGAGCAAGAGAAGGTAGAAGAAGCCAATGAAGGAGAGAACACCCGCTTGTTACACCC TGTGAGCCTGCATGGG

ATGGATGACCCGGAGAGAGAAGTATTAGAGTGGAGGTTTGACAGCCGCCTAGCATTT CATCACATGGCCCGAGA

GCTGCATCCGGACTGTACTGGGTCTCTCTGGTTAGACCAGATCTGAGCCTGGGAGCT CTCTGGCTAACTAGGGA

ACCCACTGCTTAAGCCTCAATAAAGCTTGCCTTGAGTGCTTCAAGTAGTGTGTGCCC GTCTGTTGTGTGACTCTG

GTAACTAGAGATCCCTCAGACCCTTTTAGTCAGTGTGGAAAATCTCTAGCAGGGCCC GTTTAAACCCGCTGATCA

GCCTCGACTGTGCCTTCTAGTTGCCAGCCATCTGTTGTTTGCCCCTCCCCCGTGCCT TCCTTGACCCTGGAAGG

TGCCACTCCCACTGTCCTTTCCTAATAAAATGAGGAAATTGCATCGCATTGTCTGAG TAGGTGTCATTCTATTCTG

GGGGGTGGGGTGGGGCAGGACAGCAAGGGGGAGGATTGGGAAGACAATAGCAGGCAT GCTGGGGATGCGGT

GGGCTCTATGGCTTCTGAGGCGGAAAGAACCAGCTGGGGCTCTAGGGGGTATCCCCA CGCGCCCTGTAGCGG

CGCATTAAGCGCGGCGGGTGTGGTGGTTACGCGCAGCGTGACCGCTACACTTGCCAG CGCCCTAGCGCCCGC

TCCTTTCGCTTTCTTCCCTTCCTTTCTCGCCACGTTCGCCGGCTTTCCCCGTCAAGC TCTAAATCGGGGGCTCCC

TTTAGGGTTCCGATTTAGTGCTTTACGGCACCTCGACCCCAAAAAACTTGATTAGGG TGATGGTTCACGTAGTGG

GCCATCGCCCTGATAGACGGTTTTTCGCCCTTTGACGTTGGAGTCCACGTTCTTTAA TAGTGGACTCTTGTTCCA

AACTGGAACAACACTCAACCCTATCTCGGTCTATTCTTTTGATTTATAAGGGATTTT GCCGATTTCGGCCTATTGG

TTAAAAAATGAGCTGATTTAACAAAAATTTAACGCGAATTAATTCTGTGGAATGTGT GTCAGTTAGGGTGTGGAAA

GTCCCCAGGCTCCCCAGCAGGCAGAAGTATGCAAAGCATGCATCTCAATTAGTCAGC AACCAGGTGTGGAAAGT

CCCCAGGCTCCCCAGCAGGCAGAAGTATGCAAAGCATGCATCTCAATTAGTCAGCAA CCATAGTCCCGCCCCTA

ACTCCGCCCATCCCGCCCCTAACTCCGCCCAGTTCCGCCCATTCTCCGCCCCATGGC TGACTAATTTTTTTTATT

TATGCAGAGGCCGAGGCCGCCTCTGCCTCTGAGCTATTCCAGAAGTAGTGAGGAGGC TTTTTTGGAGGCCTAG

GCTTTTGCAAAAAGCTCCCGGGAGCTTGTATATCCATTTTCGGATCTGATCAGCACG TGTTGACAATTAATCATC

GGCATAGTATATCGGCATAGTATAATACGACAAGGTGAGGAACTAAACCATGGCCAA GTTGACCAGTGCCGTTC

CGGTGCTCACCGCGCGCGACGTCGCCGGAGCGGTCGAGTTCTGGACCGACCGGCTCG GGTTCTCCCGGGACT

TCGTGGAGGACGACTTCGCCGGTGTGGTCCGGGACGACGTGACCCTGTTCATCAGCG CGGTCCAGGACCAGG

TGGTGCCGGACAACACCCTGGCCTGGGTGTGGGTGCGCGGCCTGGACGAGCTGTACG CCGAGTGGTCGGAGG

TCGTGTCCACGAACTTCCGGGACGCCTCCGGGCCGGCCATGACCGAGATCGGCGAGC AGCCGTGGGGGCGG

GAGTTCGCCCTGCGCGACCCGGCCGGCAACTGCGTGCACTTCGTGGCCGAGGAGCAG GACTGACACGTGCTA

CGAGATTTCGATTCCACCGCCGCCTTCTATGAAAGGTTGGGCTTCGGAATCGTTTTC CGGGACGCCGGCTGGAT

GATCCTCCAGCGCGGGGATCTCATGCTGGAGTTCTTCGCCCACCCCAACTTGTTTAT TGCAGCTTATAATGGTTA

CAAATAAAGCAATAGCATCACAAATTTCACAAATAAAGCATTTTTTTCACTGCATTC TAGTTGTGGTTTGTCCAAAC

TCATCAATGTATCTTATCATGTCTGTATACCGTCGACCTCTAGCTAGAGCTTGGCGT AATCATGGTCATAGCTGTT

TCCTGTGTGAAATTGTTATCCGCTCACAATTCCACACAACATACGAGCCGGAAGCAT AAAGTGTAAAGCCTGGGG

TGCCTAATGAGTGAGCTAACTCACATTAATTGCGTTGCGCTCACTGCCCGCTTTCCA GTCGGGAAACCTGTCGT

GCCAGCTGCATTAATGAATCGGCCAACGCGCGGGGAGAGGCGGTTTGCGTATTGGGC GCTCTTCCGCTTCCTC GCTCACTGACTCGCTGCGCTCGGTCGTTCGGCTGCGGCGAGCGGTATCAGCTCACTCAAA GGCGGTAATACGG TTATCCACAGAATCAGGGGATAACGCAGGAAAGAACATGTGAGCAAAAGGCCAGCAAAAG GCCAGGAACCGTAA AAAGGCCGCGTTGCTGGCGTTTTTCCATAGGCTCCGCCCCCCTGACGAGCATCACAAAAA TCGACGCTCAAGTC AGAGGTGGCGAAACCCGACAGGACTATAAAGATACCAGGCGTTTCCCCCTGGAAGCTCCC TCGTGCGCTCTCC TGTTCCGACCCTGCCGCTTACCGGATACCTGTCCGCCTTTCTCCCTTCGGGAAGCGTGGC GCTTTCTCATAGCT CACGCTGTAGGTATCTCAGTTCGGTGTAGGTCGTTCGCTCCAAGCTGGGCTGTGTGCACG AACCCCCCGTTCAG

CCCGACCGCTGCGCCTTATCCGGTAACTATCGTCTTGAGTCCAACCCGGTAAGACAC GACTTATCGCCACTGGC AGCAGCCACTGGTAACAGGATTAGCAGAGCGAGGTATGTAGGCGGTGCTACAGAGTTCTT GAAGTGGTGGCCT AACTACGGCTACACTAGAAGAACAGTATTTGGTATCTGCGCTCTGCTGAAGCCAGTTACC TTCGGAAAAAGAGTT GGTAGCTCTTGATCCGGCAAACAAACCACCGCTGGTAGCGGTGGTTTTTTTGTTTGCAAG CAGCAGATTACGCG CAGAAAAAAAGGATCTCAAGAAGATCCTTTGATCTTTTCTACGGGGTCTGACGCTCAGTG GAACGAAAACTCACG TTAAGGGATTTTGGTCATGAGATTATCAAAAAGGATCTTCACCTAGATCCTTTTAAATTA AAAATGAAGTTTTAAAT

CAATCTAAAGTATATATGAGTAAACTTGGTCTGACAGTTACCAATGCTTAATCAGTG AGGCACCTATCTCAGCGAT CTGTCTATTTCGTTCATCCATAGTTGCCTGACTCCCCGTCGTGTAGATAACTACGATACG GGAGGGCTTACCATC TGGCCCCAGTGCTGCAATGATACCGCGAGACCCACGCTCACCGGCTCCAGATTTATCAGC AATAAACCAGCCAG CCGGAAGGGCCGAGCGCAGAAGTGGTCCTGCAACTTTATCCGCCTCCATCCAGTCTATTA ATTGTTGCCGGGAA GCTAGAGTAAGTAGTTCGCCAGTTAATAGTTTGCGCAACGTTGTTGCCATTGCTACAGGC ATCGTGGTGTCACG CTCGTCGTTTGGTATGGCTTCATTCAGCTCCGGTTCCCAACGATCAAGGCGAGTTACATG ATCCCCCATGTTGTG

CAAAAAAGCGGTTAGCTCCTTCGGTCCTCCGATCGTTGTCAGAAGTAAGTTGGCCGC AGTGTTATCACTCATGGT TATGGCAGCACTGCATAATTCTCTTACTGTCATGCCATCCGTAAGATGCTTTTCTGTGAC TGGTGAGTACTCAAC CAAGTCATTCTGAGAATAGTGTATGCGGCGACCGAGTTGCTCTTGCCCGGCGTCAATACG GGATAATACCGCGC CACATAGCAGAACTTTAAAAGTGCTCATCATTGGAAAACGTTCTTCGGGGCGAAAACTCT CAAGGATCTTACCGC TGTTGAGATCCAGTTCGATGTAACCCACTCGTGCACCCAACTGATCTTCAGCATCTTTTA CTTTCACCAGCGTTTC TGGGTGAGCAAAAACAGGAAGGCAAAATGCCGCAAAAAAGGGAATAAGGGCGACACGGAA ATGTTGAATACTCA

TACTCTTCCTTTTTCAATATTATTGAAGCATTTATCAGGGTTATTGTCTCATGAGCG GATACATATTTGAATGTATT TAGAAAAATAAACAAATAGGGGTTCCGCGCACATTTCCCCGAAAAGTGCCACCTGAC

Nucleotide sequence of sgRNA for mouse KCNA1 (SEQ ID NO: 13)

TGCGAATACGCCCACGCGAT

Nucleotide sequence of 600bp promoter region where sgRNAs have been designed for KCNA1 (SEQ ID NO: 14) tgcggagagcgaagggaactggagagccatgtagatccaggctctcgcccgcccgcctcc ttcgggatcgaatcaagggctcccatagtgttaggagggggcga gagtgctgtttatcgtcatttgcctcggagcttcgagagagggtggtattttgcttttcc gccccgcatcctccggaactccctgcaccggagagaggacggcgtctccag gttgctggcaaccggtgagaatgggggtagggaaggaacattttcgccgtagctgctccg taaagcgattgtccaactgagaggggcgtcggacgagtggaccag ggcggcgagtttgcccggcgcgtctcggatgctgctgcggcggccgccgcggctcccgcc agggcactgcaaagacgacctgccgcattcccactcgggctctcc gctgactcagcaccgcccctgcgccaagccagccggccaggtagggggttccccagctcg gggatgcagaagcgggggttggggggaccgggtgggggagg ccgggggtgcggggatgctgtccgggaccctgagcttcccccggcgtctctcggcgcttt tccgatctctagtt

Nucleotide sequence of 600bp promoter region where sgRNAs have been designed for GABRA5 (SEQ ID NO: 15} cgtcaccccagaggcgctctccgacctgcagcccccagggctcctggccctttcccgttt gccactgcggcttgttgtcaagaaatggaacttcagaaaacccccaga tatacactgcgttaggtaaggatttcattctaatcgagtccaatgtgaccctggctttcc ctcccgtagttatgcattcctgtctatgagtgagatgaaaagaatgtccacag gccagcttctttcagaagcgcctaagagatgcgcatgtaaggggtgccatggagcacccg ggaaggacccaggcctgggcagggaggcgttggggccggctcta gggagcaaagctgtcggagtccaggcctctatcacccgactgctgacactgccctcccat ccctgctctacaagcgggcggtggtgactacacgaggcgccgaag atgctgttgagggccctggagaaacttcagcagaacagggcctctccccttgcaggccga gccgggggccctgcgccctccccctccgcccagctcggccaaggg cgcatttgctgagcgtctggcggcctctaccggagcacctctgcagagggccgatcctcc agccc

Nucleotide sequence of 600bp promoter region where sgRNAs have been designed for KCNA2 (SEQ ID NO: 16) aagtgcagctggcagcataaccatgtctggtaaatagcgcgggttggtaggacctgaacc acttgggacggccgggctgcattcgcctcttcggcacagaataaca aacggctttgctgcagagagggctttccccttcgctggggccgtgggctgccgccgagcc cccgcgcttaaaaggaagctgagatctggggcggcagcctggcgc aggctactccccacccccagagatcaggttccgggattttgggttggacactgagcctcg gcggtccctcggctggacgccgggggcttaagagctgaactgcgctt gggcccgcagcaggagccgaccgcgcgggcaggagggggttaaggtggcgctagcggccg cggccagcgggagggtctggtcctctgcgcggaggcgagc gctgagtgcgccgaacggaatcccggccggagcccggggcgatggggagagggcccagac ccctccccgccctggggccggcgggattgggtcggcagggg gccagtccggaagccggcttcctccaggctccccctctcgctgctgccaagccgcctcgc agctaggcaggcggagcgttt

Nucleotide sequence of 600bp promoter region where sgRNAs have been designed for LGI1 (SEQ ID NO: 17) ggtggattatacacagagagggtcccgcacttctgtttcccttccttgtcatggaaggag agaatgaattacgtgggggacccagggggataggaaaatcaatcattc atgacagttaataagtgtcagaaaagtatgtactcacattcatcccctgaaagtcacatt cttcatctgttctgatttgtctttcactgatggcattagccaggtaggctcagc aagaaacatcaaaaggttttagcccaatattgtggagagagtttcatttagcttcatttt ttccagccggggctggctccaaagctagtttttcttactaggttgtttgctacatg aaaagcagactcccagaggtttctgagattgccgacatcctatgcaagatgactgctccc acccacccgcccacccactcactaataagacataatgccgtcctatttt tggtaacaattaaagggcctcccggtgaaagcagaaagctgtttattttctgtgacatca cttcactttgccttcgaaggctggtctgtgctcagtgttttcgtggtgatgcaa gtcggctctctcctccagcagttggatccctcccatctc

Nucleotide sequence of 600bp promoter region where sgRNAs have been designed for KCNC1 (SEQ ID NO:

18) aaggagtccaaaggggttaataggggtccaggattgattgttagtggagggcgtagagga taacgtggtgtgtgtgtgtgtgtgtgtgtgttggggttcatgcaagacat tacccatggaaggaacatggggcctccaggttccgcgagaagggtcggtattaaaggatt ccttggagcggtcagcactggtccgggccagggtgtctctgatgac aaaactccgggagagctttgtctcaccagggatcagatggtccctggtttggaaggcaag gggagggtgccaacgcccttctcacctcagtctgacccgggggcgc gggcccagacgtctctcggagcccccgcccctggagtggcgttccccgagggcggaccgt gggcgggtcccccgggagcagcaggagccgcgcggggcggg cgcccccagcgccgaggttgagggaggccgggctcggtgcggggctgggaggggggcgcg gaatcagggctttttaggacccagcgcggcgccttcctccggg ggcgagtgcggctgcgcgcgccgtgtgcccgtgtccggagagcggcgggctggacgcgga ccgcgcgaacgagc

Nucleotide sequence of 600bp promoter region where sgRNAs have been designed for KCNMA1 (SEQ ID NO:

19) acggggacgaggaggagtcggaggcggcaaggaggaagagcgagcggaggccgaggggct cagcggcgtggcgacaggactagggggtcccgagaac atgggctagcaggcggccacgggccggcggccggacgcggtgaacctgccgcggccgggc gcgcactggcgcggcgagccggagccgagcgcagccggg ggaggagggctggcgcaggggcgcccgggcggagggggccgattatccattattaacgag ttaccacctaataagcggagagcggctcgttagccgcgcggga ggcgctcggggaagggggtcaccggccgagcgcagcgcacacccgtggcgcacggcgggc ggcgcggcgccgaggacacccgggaccgcgcgcggagc cggggcgggcccgggggcggcgcagaccccgggcgcgggcggcccgcggcgccccctggc tctcggcgctcggggccagcgcagcccggggcgagcggg gcgcgggccggggagggggagctgcccgcgcactccatccccctcccccccgggcgggcg gcggcggctcgctgtatatatctcggcgcaccccgccaggtcg c

Nucleotide sequence of 600bp promoter region where sgRNAs have been designed for KCNK2 (SEQ ID NO:

20) atttagataaggtaagataaaaaataaaagcctatatggaacgcagccaacgattcatct gtttgcattaataggttccagcaatggttctacaggcacggaaagcca agccggtttgccactgcacttagcaagcacatgagcttaaaaataaacttttgacaatgc agatctctttgtccttttgggaatggaaaacattatgtacttcaaagcatac taagcctgatttgaaaatatagttgggatattgttactgtggcagttgggagggtcttta gccttcacacagtgcgtggatgcttcgtgtgtaaatgcttgagccacaaactt gtgagaataagtgacgctggcaactttgatatgctcattcataaggaagaaacttctgtc ttttaaattctctggaacaactgggatatagttcctcattttaatcagggaatt tcttcctgaaccagactgtaaaaacagaggatttgagtagcacatttcacttgcatacag cagcgtttgttcgttttgagtgtttttgtacaggaaactgatctacagggtaa cattcacacacaaaaaggaaacagtatgggacgatggctt

Nucleotide sequence of 600bp promoter region where sgRNAs have been designed for KCNQ2 (SEQ ID NO: 21) cgtccactcccagggcccagctgagaagactccagtcctgctcaggcggctgggcaccgc tctgggaccccaggagcgctggggccaccaggcaggtccacttg gttagtactaccggactcaaaggtgaccgcagggtcagtgtgcacatggccgggggattg ggcaggctcagcccagagctctggtcccgcgggccttggtcccttct gcctccccctcctctccccctgccctcccctccccctcccccactccccctcctctcccc cctcccctccccctccactcctgtctcccccctccactcctgtctcccctctcc ccgtccccgccactctcctcccctcccattcccctctcctcccctccccctcccctcctg tctcccctctccccgtcccctctccctcccctcccctccctttccctcttctctcct cccctctcctctccttcccccctcccctcccctccccgtccctccctctcccctcccttc ccctccctctcttctcctcccctctccttcgactggcgtcgcgggggttaacgcg gggcggggcgaggcggcgggcggagccggcgcggccgcgggcc

Nucleotide sequence of 600bp promoter region where sgRNAs have been designed for KCNQ3 (SEQ ID NO:

22) aatcaaagattctgactgcatttcttcagtcctttgcccacccagacaggtgaaggtgct attcaaagattgggggaggagagggccgcggcatccaccatgaacca cgaactagagggaagagggaagagggaagagggaagagggagtcacgagcttcgctacca cagagcaggtgcgttcgcggtgcgcccggccttgaccaacc cgacaacttggcttttacctctgaagccgaggagcaggggtagggggtgagggaaattca caaagctgcaaccacagagccaatgtttggtgggcgacaaccccc cagtccctcctcccttcctcttcttcccccaactgcccgccgtcacgccccatccagggg aagccccaacgcccacgggagctccaggagccgggctctgcagccg cctggcgcactgcctggttgcaacgggggcggcggtagcccaggcgatcctgggtcccca gacaatcagcggtgggggtcggcgggaagaggcggggcgccg ccgcccgggcctcccgccgcgacggggcgggacaatggggccccaccccggggaaggagg gagggagggacgcggcgtg

Nucleotide sequence of 600bp promoter region where sgRNAs have been designed for KCNJ6 (SEQ ID NO:

23) tcagtaaggtcttccttttaatgaaaagcagcccccaaatcattttcttttctaacaaaa agcaacctggaaaatcgagctgcagacacagacaagcaagctgaaagc ttgcacaggcaaataccggcagttgtgccaataaaaatatactacctggggccggcgctg tggctcacgcctgtaatcccagctactcaggaggctgaggcaggag aatcgcctgaacttaggaggcggaggctgtggtgagccaagatggcgccattgcactcca gcctgggcaacaagagcgaaactccgactcaaaaagcgacaac agcagcaacaacaacaacaaaaaacactacctgggattaggcatgttctaaatggcagct ccatcttctctttttgccacccatgtttacagaaacgagtggacaaga cggcccctgccaagtgggaagcctatttgcataacaagattagggtggggtgaccagcct tccctgcgcgctacgtaaacgtcacccctggtcgaaccaatctctgg gctccacgtaaatcagacaccgcctcctcaagcctgcccgtaaaacctgctgccgtcagt cacgggcc

Nucleotide sequence of 600bp promoter region where sgRNAs have been designed for GRM3 (SEQ ID NO: 24} tgcggagagcgaagggaactggagagccatgtagatccaggctctcgcccgcccgcctcc ttcgggatcgaatcaagggctcccatagtgttaggagggggcga gagtgctgtttatcgtcatttgcctcggagcttcgagagagggtggtattttgcttttcc gccccgcatcctccggaactccctgcaccggagagaggacggcgtctccag gttgctggcaaccggtgagaatgggggtagggaaggaacattttcgccgtagctgctccg taaagcgattgtccaactgagaggggcgtcggacgagtggaccag ggcggcgagtttgcccggcgcgtctcggatgctgctgcggcggccgccgcggctcccgcc agggcactgcaaagacgacctgccgcattcccactcgggctctcc gctgactcagcaccgcccctgcgccaagccagccggccaggtagggggttccccagctcg gggatgcagaagcgggggttggggggaccgggtgggggagg ccgggggtgcggggatgctgtccgggaccctgagcttcccccggcgtctctcggcgcttt tccgatctctagtt

Nucleotide sequence of 600bp promoter region where sgRNAs have been designed for GDNT (SEQ ID NO: 25} gttgggacccgaggcaggggaatgcgcttgattttatttccaaagagaaacaccgtcctt gcttgggccgagggctcgttcaggggcctataggagctaccgggaca agaaggggaggtctctggttggggtggaggacgaagggtgggaactacccgattgccccc caggaatgggggatgttgcgcaccagtagaggggactggacag gaatcgtggtggtgggggtggggggttaactggaggggacagcagccctgcttgaaactc tgacccctaagaccgtgtggtggagaagggcagctgcaacctgaa ccaggagtgcgagctgctcctggggcgcgctgaggagggagaagcgaactggggacttgc aaggagggcaggagtgcccgaggagccgctggcctgcagcg gtgccggaggagggcggtgacgaggttggagaggggcgcagggacccgcagggagcccag gcttaacgtgcattctgcggttctctcccccacctcccgcctgc ccgcgcaggtgccgccgccggacgggactttaagatgaagttatgggatgtcgtggctgt ctgcctggtgctgctccaca

Nucleotide sequence of 600bp promoter region where sgRNAs have been designed for NPY (SEQ ID NO: 26) tggggagcgcagctttgggaccctctagccggagacttccggcagctgcctccgacttgt tctaagtacaggaaaaatctgtgcgcccagttgcctcactccaacagc gcgcagttgtgcccggcgaggatgccgcgctagtcgtggagatgccccaccacaaagagg attcaggtgcttcctactccggcacccagtgggttggtagtcctgttg gcaggagacaagaatcgtctgggctgctcctatctctggcaggactagacggggcgtgaa ggaaagaaggaaagaaggaaagcagggatcgggcactgcccg agggcagatacttgggctttggtgttgtccagcgcgctcggagtgcgctgcctcgctcac gcggtcccaggccccgcttcttcaggcagtgcctggggcgggagggtt ggggtgtgggtggctccctaagtcgacactcgtgcggctgcggttccagccccctccccc cgccactcaggggcgggaagtggcgggtgggagtcacccaagcgt gactgcccgaggcccctcctgccgcggcgaggaagctccataaaagccctgtcgcgaccc gctctctgc

Nucleotide sequence of 600bp promoter region where sgRNAs have been designed for NPY2R (SEQ ID NO: 271 gagcacagggaccgcccagctagaggagcaccagcgcactgcgccccagccctgggcgag ggtgcggaggatttgttctcggtgcaatcctgctggcgcttttcc ggggttctgcgcggatccagctccccatctctgctcctacacacacaaaagaaaacaact ctcgattggaagttgtggaattttctcagcccctacgaggcgcgggga ttctccagccccggccctcctcccgccagcctgaggtctccttcgctcgcctgccttgct agggaccgcagtccctcagccgcagctgggtctgtccgccccgcctttgc cctcgccttttcccggggcggatttggtgaagtcggcctcaagtccaggaggtctgtctt cgccgggccagctctcgcggaactggggggtagagagcaaagggag agattcgtggaagggaagggaggtaggggtggcgcaaacgcccagagtatcaaacttggg ggtggcacagtaggtgacagcagcagctgcaggtggtggctgg ggacccgcgagggggcgcccctctgggtagggtctggctgagcgggcttgcaagcccggg aggcggct

Nucleotide sequence of 600bp promoter region where sgRNAs have been designed for GALP (SEQ ID NO:

28) tccggcctagggacgcagccatgaacaagacacagttgacacccctcatggggtctcctt tagccagggtggtaggtggggggcggggagatagacagctcaca agtaaacaaataaacagggtctaccgtgcaagacagaagaaatgcaactcagtgagggag ctgcggaggcttggagggattgatgggggcagaggggacag ggctacggagacaccagtggcaggtggagacaaccaaggaagacacaggtcaaggcccag acgcagataagagggagggagggagccctcgaatagctg caaagtctggaacaggacagctggaagataaaggggcacagaaggagggggaagggcagg gtctaccaggggaaaccaaggcacagcagcatttcccgcg atgaagtgtgtgttttgacctcacagaccagcgtttgaaagcccctggagtggatgactg ttcccccacctccatcctcttcactccctctcccttcttctaatcccctcccttt cccccctcccttctattgtctcctcagaaggcataaaagctcagggggcgtgaaagagtc caggcgctggagcgaggagcc

Nucleotide sequence of 600bp promoter region where sgRNAs have been designed for GALR1 (SEQ ID NO:

29) aaaagagctctcgccctgtggacgactcggaatccctggaaaagccgggagggagtcgga ggcgccagcccactggggaggtggcgctgggcgcgcgggatg cgcggggagccttctctgcaggagccgcacagtgcactgctgcgcgctgggcagtgcggg gaagcgccgcgggaaggagcggctccgagcaacaggtgcagc acgcagcccctccgggagccagggaaaaccgccggcgaagatctggagcggtaaggcgga gagaagggtctttccacctgcgcggctgcagccggcggatcc ctcttcccaggctccgtggtcgcgcagcgggcggaggcgcccgggaaggggaccccagtg ctctcgagatcaccgtcccttcccgagaaggtccagctccgggct cccgaacccaccctctctcagaaggtcccggcgcaaagacggtgccaccaggcacggcca ccggatccccgctcccgctggctcgcgcctcgggggaagctca gactcctaaactcgcactctccgtgctttgcgccgggacccctggccacccccggcgcct actatcccgccctccctccccgcgcg

Nucleotide sequence of 600bp promoter region where sgRNAs have been designed for PDYN (SEQ ID NO:

30) actgtctcagcctctgtctgtctccacgtctgtctgtctgtggatcagtgtgttttgagt ctgacagtctacctggctggtttccttttttcttgctctgtccctctctccttgtgtttc tac ccatctccctatctctgccactctctgtctctgtttttctttctctttctcccctccttt gtatcactccctaggtccgacattgcctctttctcgatttccgattctctctgagtctct ctctc tctctctctttctctaactcttctgtctctgtccttccctgtcttctttttcctgtgaca ctctcctggaaacgcatcaaaaactgaagtggccggatttcaagtgacaaacagcac tacacccagaatccgccccctccccaacacggctgccttcctcctccacatccctgtcac gaagagaagcctattgtgtcaggcccagggagttcgagttgaagggc ctgggggtctgtgctctgactgctctcagccacttccccattggctcccagcagcctgtg ctcagcaagggctgagcgacaggggaggctctcgtccataaaagggg ggaagaggcaccagaactgcc

Nucleotide sequence of 600bp promoter region where sgRNAs have been designed for BDNF (SEQ ID NO: 31) gagtaaaccaatagcccccatgctctgtgcgatttcattgtgtgctcgcgttcgcaagct ccgtagtgcaggaaggtgcgggaaggtgtgtctgtggcccgggaaacg cacgccctctcccagagaacttgggtgctgggatggggaggaaggggagagttgaaagct aggggagcgagacctcggggcgtgcgattctcactcgctccctcc cgccccagcgcccacagccggggtttctgcagagggcgcgggacgcggggttccccgggg ctgaggctggggctggaacacccctcgaagccgcgggcgtcct gtccaaggcgccccaggagggcgcaggactcgcagggcgatgtcgcggggccctagggga ggaggtgaggacaggccccgggggagcggggagttccggg cgcccctcggttccccgcgcgaggaaaagacgcggcgttccctttaagcggccgcctcga acgggtatcggtagcgcgggcgagcggggagcggggggcggg gggcgggggggggggggcggcgccgtttgaccaatcgaagctcaaccgaagagctaaata atgtctgacccgggcgcaaggc

Nucleotide sequence of 600bp promoter region where sgRNAs have been designed for FGF2 (SEQ ID NO: 32) ttggtagacgacttcagcctctgtcctttaattttaaagtttatgccccacttgtacccc tcgtcttttggtgatttagagattttcaaagcctgctctgacacagactcttccttgg attgcaacttctctactttggggtggaaacggcttctccgttttgaaacgctagcgggga aaaaatgggggagaaagttgagtttaaacttttaaaagttgagtcacggct ggttgcgcagcaaaagccccgcagtgtggagaaagcctaaacgtggtttgggtggtgcgg gggttgggcgggggtgacttttgggggataaggggcggtggagcc cagggaatgccaaagccctgccgcggcctccgacgcgcgccccccgcccctcgcctctcc cccgcccccgactgaggccgggctccccgccggactgatgtcgc gcgcttgcgtgttgtggccgaaccgccgaactcagaggccggccccagaaaacccgagcg agtagggggcggcgcgcaggagggaggagaactgggggcg cgggaggctggtgggtgtggggggtggagatgtagaagatgtgacgccgcggcccggcgg gt

Nucleotide sequence of 600bp promoter region where sgRNAs have been designed for GABBR1 (SEQ ID NO: 33) taccccttccctcgtcttttctcaattccatgtcctgtctccctttcttaggcttctgtc tacccagccccaggctcccttccacgaccccaccactccctcaaaccagcctccct tccgtacccaactcgttccctccaaaaccgtttcctctcccccacatcctcagtgcttca ctgtatcgactcatactcccacttcagacctcaggcgccagccccgtttctct cccgtcccactcgcatccttcccttcctaccctggttcctccgtgcttcagcctcccgcg gctccctccgcccaccccgccctcctggcacgccccgtccccatttctcctc ccctcgggtccccttaagtgagatccctcccttcctctttcgttcctttcctcctcgagg ttgcatcccccctcccctccccgcccctccgactgtcgctcccacctcggcgct cgcttccctccccgcccccttcctgcctccccagctcccgcccgcccccccaccccccgc tgccgcgcgccgcccgtgacgtcagagccccctcccagccccacat ctccctcctgctcctcctcctcccctccgtcggtcagtc

Nucleotide sequence of 600bp promoter region where sgRNAs have been designed for GABBR2 (SEQ ID NO: 34} ggacgccttcgtggaacattctcctgcccagaccttcccggccagacctccgagaagcgg ttccaaaccaccgtgcaggtgctacaggcagcgctcggcggagcg gcggcggccactgcgtgtgccagcgcgcggtcccggttcccagatcgctgtccccgggcg ctctggtgcctggaggtcagcggtcggcgggcagcggcagctggc gcagcggagggccgggggcgcgtgtgtgcgtgtgctgggaaggtggccctccccgcggcc gccgcagcgccagcgcctccccctcccccggcgcgcacggctc gtccccgtccctggaggcggcccgagccgcccctgagcagcctcgccttcgcctcccgcg tttcctgccgtccgccctcccccggccgagctccaggggctgccgc ctagcagctcccggcgggagagcggttcagagcgcgcacgggggcgggcggaggcggccc ggtgcggggcggccgcgctggagagaggcgcgcgcggag acgccggcccccctctccgcgtttgctcgcttgctccccgcctcccgcactccgctcgct cccaccccttcccggcgtgatt

Nucleotide sequence of 600bp promoter region where sgRNAs have been designed for GRM3 (SEQ ID NO:

35) gtgtctggcttcatataattcagtccttggttaatacaaagttagtatattagagtacaa aaattaatgaagtttcaatttggaaattaaacagtatgtgtttctagacatagaa agatgcctggaattttacctttaggattttatctgtagctggcagcctattaaagctgtt tccgcgtgcctttttctcttttgtgcctacgtcaccgatttaaggttcctatttatttat tt atttttaagaagaaagaagaggttctgtaggaaacattgactgtatccgacaaccatagc aggactagagaaggaccaatgagggggtgctgggggtagctttaag aggcgaggtggtagcagaaaaggataagaagaaagataattcagcagtcccctataatct tattccacccaagaaatttgggagaatgcgaaaaagcagcagcc cagcattcccggatgggcgtggcttttctccaggggctgtccaattgaattccttcagag ggagaagattgataagggttgctaggaaacaggagcgtctgcctcccgc ctgacccagagattgttctgcacaaaccctctccaggggctcgc

Nucleotide sequence of 600bp promoter region where sgRNAs have been designed for GRM4 (SEQ ID NO:

36) ccatccagtgctggagggagaccagcgggtggggtgtttccctagcctggtggggttttg aggtggtaagggggctctgtggaaagtgtcccctggacaggctgtgag atctggggcaagtggagtcacctcactgggcctcagtttctccccttgttatatacttga atcaggagcagtggggtgtgcaaatgaacatgccacatgggggcatacg ccacgtgcgcgcggatgtgtgaggttccagtgacgcaccagggtgggagtagcgcgcccc tctgcgtccctgtgctttgctgtacttttctgggtgtgtgttagggaggct atgttcctgaccctccccctctggggtgagaaggggtccccgccatgtcctcggggtagg tgagctggcacgcgcacggggaggaggaaggggggggcttccgg aagagggcgccggtggggtgtggtggaagggggagctgccagcagggcgggtgtggaggg gtggcggagcgccgcgagagccctggccttccggaggtgga ggtgtggggtagggggtgggctccaggtgctctctctttaaaaggccggcagaagcgccg tgagctt

Nucleotide sequence of 600bp promoter region where sgRNAs have been designed for GRM7 (SEQ ID NO:

37) tcagctcctggccctggaaacccctttgggtaaagcgtctttaagtcaagaatcaggctc ctgtgtgcacgtgtggctttcttagcaaaaaactagcacaggcggctca ggagtagagtctagctagggtcttcccgcgcccctccctcactggtttctctgcccctgc ctcgctttctcccagagctaagagcctaggctccggacctagggtttggga gcagtcagcacgacgtcctcgccccatcccgcggctgatgacacccgtgcccagaacgtg ggtgtgggtagggaggcttccacagtgagttagggtcgagagcta ggctctcgcttgctccccgcaatccctagattccctggggaccacgaaactcccattccg aggaaacctccccccattccccagccgcccacccgtttcccccccttac ctcagcacgcagcccctccctgcgtgatgatgcaaaccagtggggagggctggcgctggg aagggtggggagagaaggagagccagcgagggagggaggg agtgggaggaggaggagagggagccgaacgaccatttaaagcgatagcagtccctgccct ctcccc

Nucleotide sequence of 600bp promoter region where sgRNAs have been designed for GABRR1 (SEQ ID NO: 38) tacgatctgggaacagaaccttaaaacaactgcatttcaaataacccgaaaaaaatttct ctcatcaattttttttcagtcttgtgtaattaattctcattctattggatcttgggt tagcagttgtgtgaaaccgcttttcagctatagagttatgggaatcctgactcagtttac cggtacagtctgaaagttaccaaaaccatgtcagctcagctttgaagagtc aatagtttggagtacctaatgcggtctcttccacgaggctctgagactgtcttttgatga agacacaagatccggcctgtagattatagcagagtcttaaagtaagcatca aagcaaaagaaaaactgtctacaaataacacagacttgaggctacagttaatttattact ggtatttttcaaatgtggacagtgcagcaaggttcatgataagaacaat gcaactgacaaggaaatttacttgtttctgcgccaaacaaagacaaaaaaacctcttccc cagttgccctcccaatctcagccatatagacagcccacgcaggtacc gagccctggggtttcagggattcagccacaggaagtgggggcagg

Nucleotide sequence of 600bp promoter region where sgRNAs have been designed for GABRR3 (SEQ ID NO:

39) aaatggctttcttcctaagtcctagtaaaaaggtcaaccgttgctgtgttgctcaccttg tgctattccagttgaagaagattaatttcaatgacatgaccatttattggtgcttt gcatatgtgaagtagaaatattttcttaaatattttctctaagtatgcaaagcaccttta ggagagtgtgtggctataatttaacagtgacagtgtgtgctttgcacactgacc aggattaagttcatttttattaactgggttgcttgctattaaataaaccttaaattaaac cacttttgttatcaatgaaataaaccatcatcttaaaatatgattatttaccttaaaa aaaataattttattttgtattcatgctaaggcagtctgtatggcatttggggaggaaaag attctttctggattaaaaggagccataagataatggaaaaggtcttcaaacg tgtaattaagattaaattaatcatctttttttctcaataagcatattattttgctgagtc actaagtatatttaaatgatattgcattggattaagaggattaatgcttaacctcactt ctttgtttgcttaggactgcc

Nucleotide sequence of 600bp promoter region where sgRNAs have been designed for OPRK1 (SEQ ID NO:

40) aaggagagtgttttgcccttctcagatactatcagcaattcaggtaatacccgtaaggtg cagtttgtctgcagcctgtcatcccagttagagcagacggaatggaaga gaacgcaaggaaatattctatttatgtgtcttttaagtcattattttatgaactggtctt attctaactggatcattttgttactttctttggatgggccattctaataagcgtagttcc t gactgcgaactatgcagataagaagttctagacacaatatgaaaatccaggtgcatactt gcactaaataggcatgctcctcctttttactaaatctaaatggctcagtct caggtcttggggaaggctgcatggccggggaccaggcggtgtgccgctcgggcagttagt gggccgggcgagcctgcggggctggaggggacgcggggctgg gaggctggggagctgggggctgactccgggcgggcggggcggggcagggacctgccggcc tggggcgggcgcaccagacgagctctccgcccgcaggccc ccagcgcccagccgcgtcccggctgcgtcccgccggtcccgccccgccccgccccgc

Nucleotide sequence of 600bp promoter region where sgRNAs have been designed for OPRM1 (SEQ ID NO:

41) ttactggatgccacaaccttctgatttctgtaaccacttcttatgcctcctacccactga aacaaaatcagaggcaaacagagcttcaccctagaaattggggaaaatg aggaacaggttttctgcacaaaagtttatttgtttctcatttctttttcagaaaataaag gatcgctgttgttcccaacaggtttgtagggaagaaaattggagaaacattatt accttttcttagatgttggcaacggaggcaacaaggactgcaaaagaaaattgtgtgtcc cccattcctaaataatcaaaattggcagtagggatggaagagcattgg ggttttagggctgttagggtttcatcaagccaatgtattccctgccagattttaaggaga aaaaggcgctggaaaattgagtgatgttagccccctttcttatttttcactgcta ccaaagactaactctatctctctccccaacccttctctccatctccctcctttagatgtg tttgcacagaagagtgcccagtgaagagacctactccttggatcgctttgcgc aaaatccaccccttttccctcctccctcccttccagcctcc

Nucleotide sequence of 600bp promoter region where sgRNAs have been designed for OPRD1 (SEQ ID NO:

42) tctctcctgcactgggctgtaagccccaggaagcagaggctgcatctggttttgtgtact agagggtccccccaaatacccggctcttctattaggcaccctcagaattttt gttgagcgaatgaatggggtgcaagaaaggcacggataatataggttatttacggagcat gtaactgtccgcagggcactgctctaagctctttgttcgaatcattttatt caatctccccaaccaccctctgagggaggtggtacgattttcctcatctcacagacaaag agaatgaagctgagggaggttaagtgacttacacaaggtcactccgc ctgttagtgcaggggcgggaggcgggatccacacccaggtccctctgacaccaaagtggc aagggggtgggaggggagtccaggttgggacggggtcgcactc gagccggcggagcatccctagggagggggcgggaggcctcccctgcccagctccgagccg gtggtgcagcgtccgcccccggtcgcgggcgcagactggcgg ccgcctccgggccacgtggtgcgcgcggcgggcgcgtccgaggagcctgcggctgctcct ggctc

Nucleotide sequence of 600bp promoter region where sgRNAs have been designed for OPRL1 (SEQ ID NO:

43) ccagatccagcggggtgggggcgggggcggacagggtgtcccgccccggcccctcctcac cgggctgagagggggagggagacgcggaaacctgggttcttc cggcccccacctttgagcaatcacttccccaggctttgagctccagaaaaaggggaaccc ggctgcggcgccccctcccccacgcgcggggggcgggctccactt ccactgcggcccagggtccacgtggacctggcggcgggagcccttggggttcgagtcccg tgcgccggctcccgaagctcccgcccagcacggtccccgggccc gggccgggaggggcagggccgctgtccccggcgctgcgcgcgcgcactcaccagccgcgc tcccgagccactcgcgccgccgccggcccgcgcgctccaag gtccggcccgacagtcggggagggggcgcgggggcgcagtgcgcaggcgcctcggcggca cttccccaaagccaggggccgggacttcctcgcgccggcggt cgccgggcccgccccgcccgccgcgccccgccccgcgctcggccggctccgcaccccacc cgccccgcccgcgcgtcggcccccac

Nucleotide sequence of 600bp promoter region where sgRNAs have been designed for KCNJ2 (SEQ ID NO:

44) gggctctgcgcgcccgccccagtccctcgccccattgactcagtggcttctccgggcgct gcagcctccgcggggggcttcgaagggccgaggggctccggcaga gagggagtggagagggagacgcgccgggaccgacgaacaatcctgcccctgcggcaaagg tctctacccggcgctggcacctcgcaggcccctcgaggagc acgcagggcaagcggcccaagagcgggggaaccgggaagtgtgtggggctccagacggag taggaagctttgcccaaggccaggctgcaatcaggcagccg caacagccgggcgcggagcttcccacctgctgctgtcccagctgggccgcaacttcctcc tccccggcccgggcccgactccccggccgggctccgagggtggag ggggacgaggcggcggcaggttccctccgctggcaacgcctcgcagcatcctcccctccc cgccgcggttcccggggccggccgcgcggccaggcgcgctgcg attggccggcagcggccgggggcggggccaggagagccggtgtcgcacggaccgcctcaa aagagcccaggatattgcagagcgc

Nucleotide sequence of 600bp promoter region where sgRNAs have been designed for GABRA1 (SEQ ID NO:

45) ggtggggtggaaagcgctcccaacctgagaaagtgcgaaagactctctaaatccagtagc caatttcctacctgccagaactctttcctaccatccgtcaccattcgtg actctgcaagacacggggacttagacatatgtgtgggagtgtgtgtgtgagggagagagg cgagacgagtgctctccccacacgtgtaaccctgcatctcccagtttc agagcttgcgttcattcatatgcaggcagtggtttaatatttgatcaaaggtagaatagt tgcactaaatagttgtatttttaatgggctcaccttaaaatcgggtgttcataa attgcaagtgtgaaaagactctaagtgcagtccgtatgtctctcaccctttctacccttc cctcccccattgccgctccccccaaaaagagaagcttgcagcagattgtag aaggatttgagcctgcagctagagagaaggggattagggccagagtggtgcaagttaaat tgtgctgcatataaaaaatgggcggattggtctccagatccagagg ctggtaccaccttcctttctaaaataaaatctctctggcatgaagtcaccgc

Nucleotide sequence of 600bp promoter region where sgRNAs have been designed for GABRA2 (SEQ ID NO:

46) gaacctctttacctcttagcagccacgtcgctccacagtagggtgatgttgggggacggg cggcagggcgcggccccagggatctagggcatcaccgccacacta cattcccggctttacaccaacacccaacagcagctctgtcaggaaccttggggcctctcg ggagccccagcaagcggcctcggggagcagcccgaggctgcgcg tgggctccgctcctccggcgaggtgtgggcgaggggagcggcgctccgagcgcacccagg cgcccgacgccgcccgggtctgcgccgctgctagtgccaggcg ggcgacggtcagttaccagggatcgagggatcgaggcaggggagtgtgtgtgtgtggggg ggggggaggggggggagggggggccctgccttcccgggaacc tccttagccctcctacccggcctgactcctcctcctccaggcgcggggctcgtgcccgcc accgccggcgcgcaccgcgcctccgcccgcgtccccccaatttcccc ccccggccccagctcctgtcatcgttttccccctcctcctcttcctcctcctcctcttcc tcctcctccgcccatcacc

COMBINATORIAL CRISPR CLONING SEQUENCES

All these sequences are for the S. Aureus (sa) dCAS9

1. sgRNA sequences for in vitro screening using qPCR

1.1 LacZ

Nucleotide sequence of sasgRNA for mouse genes: sgRNA LacZ control (SEQ ID NO: 47) gTGCGAATACGCCCACGCGAT pAAV-CMV-sadCas9-U6gRNA(Lacz-sa sgRNA) used as control in in vitro gPCR experiments (SEQ ID NO: 48)

CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCGTCGGGCGACC TTTGGTCGCCCGGCC TCAGTGAGCGAGCGAGCGCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCCTGC GGCCTCTAGACTC GAGGCGTTGACATTGATTATTGACTAGTTATTAATAGTAATCAATTACGGGGTCATTAGT TCATAGCCCATATATG GAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCC CGCCCATTGACGT CAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGG TGGAGTATTTACGGT AAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGACG TCAATGACGGTAAAT

GGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGT ACATCTACGTATTAGTCA TCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAATGGGCGTGGATAGCGGTTTG ACTCACGGGGATTT CCAAGTCTCCACCCCATTGACGTCAATGGGAGTTTGTTTTGGCACCAAAATCAACGGGAC TTTCCAAAATGTCGT

AACAACTCCGCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTAT ATAAGCAGAGCTCTCT

GGCTAACTACCGGTGCCACCATGGCCCCAAAGAAGAAGCGGAAGGTCGGTATCCACG GAGTCCCAGCAGCCAA

GCGGAACTACATCCTGGGCCTGGCCATCGGCATCACCAGCGTGGGCTACGGCATCAT CGACTACGAGACACGG

GACGTGATCGATGCCGGCGTGCGGCTGTTCAAAGAGGCCAACGTGGAAAACAACGAG GGCAGGCGGAGCAAG

AGAGGCGCCAGAAGGCTGAAGCGGCGGAGGCGGCATAGAATCCAGAGAGTGAAGAAG CTGCTGTTCGACTAC

AACCTGCTGACCGACCACAGCGAGCTGAGCGGCATCAACCCCTACGAGGCCAGAGTG AAGGGCCTGAGCCAG

AAGCTGAGCGAGGAAGAGTTCTCTGCCGCCCTGCTGCACCTGGCCAAGAGAAGAGGC GTGCACAACGTGAACG

AGGTGGAAGAGGACACCGGCAACGAGCTGTCCACCAAAGAGCAGATCAGCCGGAACA GCAAGGCCCTGGAAG

AGAAATACGTGGCCGAACTGCAGCTGGAACGGCTGAAGAAAGACGGCGAAGTGCGGG GCAGCATCAACAGATT

CAAGACCAGCGACTACGTGAAAGAAGCCAAACAGCTGCTGAAGGTGCAGAAGGCCTA CCACCAGCTGGACCAG

AGCTTCATCGACACCTACATCGACCTGCTGGAAACCCGGCGGACCTACTATGAGGGA CCTGGCGAGGGCAGCC

CCTTCGGCTGGAAGGACATCAAAGAATGGTACGAGATGCTGATGGGCCACTGCACCT ACTTCCCCGAGGAACT

GCGGAGCGTGAAGTACGCCTACAACGCCGACCTGTACAACGCCCTGAACGACCTGAA CAATCTCGTGATCACC

AGGGACGAGAACGAGAAGCTGGAATATTACGAGAAGTTCCAGATCATCGAGAACGTG TTCAAGCAGAAGAAGAA

GCCCACCCTGAAGCAGATCGCCAAAGAAATCCTCGTGAACGAAGAGGATATTAAGGG CTACAGAGTGACCAGCA

CCGGCAAGCCCGAGTTCACCAACCTGAAGGTGTACCACGACATCAAGGACATTACCG CCCGGAAAGAGATTATT

GAGAACGCCGAGCTGCTGGATCAGATTGCCAAGATCCTGACCATCTACCAGAGCAGC GAGGACATCCAGGAAG

AACTGACCAATCTGAACTCCGAGCTGACCCAGGAAGAGATCGAGCAGATCTCTAATC TGAAGGGCTATACCGGC

ACCCACAACCTGAGCCTGAAGGCCATCAACCTGATCCTGGACGAGCTGTGGCACACC AACGACAACCAGATCG

CTATCTTCAACCGGCTGAAGCTGGTGCCCAAGAAGGTGGACCTGTCCCAGCAGAAAG AGATCCCCACCACCCT

GGTGGACGACTTCATCCTGAGCCCCGTCGTGAAGAGAAGCTTCATCCAGAGCATCAA AGTGATCAACGCCATCA

TCAAGAAGTACGGCCTGCCCAACGACATCATTATCGAGCTGGCCCGCGAGAAGAACT CCAAGGACGCCCAGAA

AATGATCAACGAGATGCAGAAGCGGAACCGGCAGACCAACGAGCGGATCGAGGAAAT CATCCGGACCACCGGC

AAAGAGAACGCCAAGTACCTGATCGAGAAGATCAAGCTGCACGACATGCAGGAAGGC AAGTGCCTGTACAGCC

TGGAAGCCATCCCTCTGGAAGATCTGCTGAACAACCCCTTCAACTATGAGGTGGACC ACATCATCCCCAGAAGC

GTGTCCTTCGACAACAGCTTCAACAACAAGGTGCTCGTGAAGCAGGAAGAAGCCAGC AAGAAGGGCAACCGGA

CCCCATTCCAGTACCTGAGCAGCAGCGACAGCAAGATCAGCTACGAAACCTTCAAGA AGCACATCCTGAATCTG

GCCAAGGGCAAGGGCAGAATCAGCAAGACCAAGAAAGAGTATCTGCTGGAAGAACGG GACATCAACAGGTTCT

CCGTGCAGAAAGACTTCATCAACCGGAACCTGGTGGATACCAGATACGCCACCAGAG GCCTGATGAACCTGCT

GCGGAGCTACTTCAGAGTGAACAACCTGGACGTGAAAGTGAAGTCCATCAATGGCGG CTTCACCAGCTTTCTGC

GGCGGAAGTGGAAGTTTAAGAAAGAGCGGAACAAGGGGTACAAGCACCACGCCGAGG ACGCCCTGATCATTGC

CAACGCCGATTTCATCTTCAAAGAGTGGAAGAAACTGGACAAGGCCAAAAAAGTGAT GGAAAACCAGATGTTCG

AGGAAAAGCAGGCCGAGAGCATGCCCGAGATCGAAACCGAGCAGGAGTACAAAGAGA TCTTCATCACCCCCCA

CCAGATCAAGCACATTAAGGACTTCAAGGACTACAAGTACAGCCACCGGGTGGACAA GAAGCCTAATAGAGAGC

TGATTAACGACACCCTGTACTCCACCCGGAAGGACGACAAGGGCAACACCCTGATCG TGAACAATCTGAACGGC

CTGTACGACAAGGACAATGACAAGCTGAAAAAGCTGATCAACAAGAGCCCCGAAAAG CTGCTGATGTACCACCA

CGACCCCCAGACCTACCAGAAACTGAAGCTGATTATGGAACAGTACGGCGACGAGAA GAATCCCCTGTACAAGT

ACTACGAGGAAACCGGGAACTACCTGACCAAGTACTCCAAAAAGGACAACGGCCCCG TGATCAAGAAGATTAAG

TATTACGGCAACAAACTGAACGCCCATCTGGACATCACCGACGACTACCCCAACAGC AGAAACAAGGTCGTGAA

GCTGTCCCTGAAGCCCTACAGATTCGACGTGTACCTGGACAATGGCGTGTACAAGTT CGTGACCGTGAAGAATC

TGGATGTGATCAAAAAAGAAAACTACTACGAAGTGAATAGCAAGTGCTATGAGGAAG CTAAGAAGCTGAAGAAGA

TCAGCAACCAGGCCGAGTTTATCGCCTCCTTCTACAACAACGATCTGATCAAGATCA ACGGCGAGCTGTATAGA

GTGATCGGCGTGAACAACGACCTGCTGAACCGGATCGAAGTGAACATGATCGACATC ACCTACCGCGAGTACCT

GGAAAACATGAACGACAAGAGGCCCCCCAGGATCATTAAGACAATCGCCTCCAAGAC CCAGAGCATTAAGAAGT

ACAGCACAGACATTCTGGGCAACCTGTATGAAGTGAAATCTAAGAAGCACCCTCAGA TCATCAAAAAGGGCAAAA

GGCCGGCGGCCACGAAAAAGGCCGGCCAGGCAAAAAAGAAAAAGGGATCCGGACGGG CTGACGCATTGGACG

ATTTTGATCTGGATATGCTGGGAAGTGACGCCCTCGATGATTTTGACCTTGACATGC TTGGTTCGGATGCCCTTG

ATGACTTTGACCTCGACATGCTCGGCAGTGACGCCCTTGATGATTTCGACCTGGACA TGCTGATTAACTGTACAG

GCAGTGGAGAGGGCAGAGGAAGTCTGCTAACATGCGGTGACGTCGAGGAGAATCCTG GCCCAATGGCCAAGC

CTTTGTCTCAAGAAGAATCCACCCTCATTGAAAGAGCAACGGCTACAATCAACAGCA TCCCCATCTCTGAAGACT

ACAGCGTCGCCAGCGCAGCTCTCTCTAGCGACGGCCGCATCTTCACTGGTGTCAATG TATATCATTTTACTGGG

GGACCTTGTGCAGAACTCGTGGTGCTGGGCACTGCTGCTGCTGCGGCAGCTGGCAAC CTGACTTGTATCGTCG CGATCGGAAATGAGAACAGGGGCATCTTGAGCCCCTGCGGACGGTGCCGACAGGTGCTTC TCGATCTGCATCC

TGGGATCAAAGCCATAGTGAAGGACAGTGATGGACAGCCGACGGCAGTTGGGATTCG TGAATTGCTGCCCTCT

GGTTATGTGTGGGAGGGCTAAGAATTCCTAGAGCTCGCTGATCAGCCTCGACTGTGC CTTCTAGTTGCCAGCCA

TCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACT GTCCTTTCCTAATAAAAT

GAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTG GGGCAGGACAGCAAGG

GGGAGGATTGGGAAGAGAATAGCAGGCATGCTGGGGAGGTACCGAGGGCCTATTTCC CATGATTCCTTCATATT

TGCATATACGATACAAGGCTGTTAGAGAGATAATTGGAATTAATTTGACTGTAAACA CAAAGATATTAGTACAAAA

TACGTGACGTAGAAAGTAATAATTTCTTGGGTAGTTTGCAGTTTTAAAATTATGTTT TAAAATGGACTATCATATGC

TTACCGTAACTTGAAAGTATTTCGATTTCTTGGCTTTATATATCTTGTGGAAAGGAC GAAAcaccgTGCGAATACGC

CCACGCGATgtTTTTAGTACTCTGGAAACAGAATCTACTAAAACAAGGCAAAATGCC GTGTTTATCTCGTCAACTT

GTTGGCGAGATTTTTGCGGCCGCAGGAACCCCTAGTGATGGAGTTGGCCACTCCCTC TCTGCGCGCTCGCTCG

CTCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGGGCTTTGCCCGGGCGGCC TCAGTGAGCGAGCG

AGCGCGCAGCTGCCTGCAGGGGCGCCTGATGCGGTATTTTCTCCTTACGCATCTGTG CGGTATTTCACACCGCA

TACGTCAAAGCAACCATAGTACGCGCCCTGTAGCGGCGCATTAAGCGCGGCGGGTGT GGTGGTTACGCGCAGC

GTGACCGCTACACTTGCCAGCGCCTTAGCGCCCGCTCCTTTCGCTTTCTTCCCTTCC TTTCTCGCCACGTTCGC

CGGCTTTCCCCGTCAAGCTCTAAATCGGGGGCTCCCTTTAGGGTTCCGATTTAGTGC TTTACGGCACCTCGACC

CCAAAAAACTTGATTTGGGTGATGGTTCACGTAGTGGGCCATCGCCCTGATAGACGG TTTTTCGCCCTTTGACGT

TGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAACTGGAACAACACTCAACT CTATCTCGGGCTATTCTTT

TGATTTATAAGGGATTTTGCCGATTTCGGTCTATTGGTTAAAAAATGAGCTGATTTA ACAAAAATTTAACGCGAATT

TTAACAAAATATTAACGTTTACAATTTTATGGTGCACTCTCAGTACAATCTGCTCTG ATGCCGCATAGTTAAGCCA

GCCCCGACACCCGCCAACACCCGCTGACGCGCCCTGACGGGCTTGTCTGCTCCCGGC ATCCGCTTACAGACAA

GCTGTGACCGTCTCCGGGAGCTGCATGTGTCAGAGGTTTTCACCGTCATCACCGAAA CGCGCGAGACGAAAGG

GCCTCGTGATACGCCTATTTTTATAGGTTAATGTCATGATAATAATGGTTTCTTAGA CGTCAGGTGGCACTTTTCG

GGGAAATGTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTA TCCGCTCATGAGACAATAA

CCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTC CGTGTCGCCCTTATTCCCT

TTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAA AAGATGCTGAAGATCAGTT

GGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAG TTTTCGCCCCGAAGAAC

GTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTA TTGACGCCGGGCAAGAGC

AACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCA CAGAAAAGCATCTTACGG

ATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTG CGGCCAACTTACTTCTGA

CAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATG TAACTCGCCTTGATCGT

TGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCT GTAGCAATGGCAACAA

CGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAA TAGACTGGATGGAGGCG

GATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCT GATAAATCTGGAGCCGG

TGAGCGTGGAAGCCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCG TATCGTAGTTATCTACA

CGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTG CCTCACTGATTAAGCAT

TGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCAT TTTTAATTTAAAAGGATCTAG

GTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTC CACTGAGCGTCAGACCCC

GTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGC TTGCAAACAAAAAAACCAC

CGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGG TAACTGGCTTCAGCAGA

GCGCAGATACCAAATACTGTTCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAG AACTCTGTAGCACCGCCT

ACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCG TGTCTTACCGGGTTGGA

CTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTG CACACAGCCCAGCTTG

GAGCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCC ACGCTTCCCGAAGGGA

GAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGG AGCTTCCAGGGGGA

AACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGA TTTTTGTGATGCTCGTCA

GGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCC TTTTGCTGGCCTTTTG

CTCACATGT

1.2 KCNA1

Nucleotide sequence of sasgRNA for mouse KCNA1; sgRNA1 (SEQ ID NO: 49)

TACTAGCCACAATAGAGCCAG Nucleotide sequence of sasgRNA for mouse KCNA1; sgRNA2 (SEQ ID NO: 50)

CCTTACTAGCCACAATAGAGC

Nucleotide sequence of sasgRNA for mouse KCNA1; sgRNA3 (SEQ ID NO: 51)

TGTGATCATTGACTTTGATTA

Nucleotide sequence of sasgRNA for mouse KCNA1; sgRNA4 (SEQ ID NO: 52)

AGGGGCCTCTAGAAGGATCCC

Nucleotide sequence of sasgRNA for mouse KCNA1; sgRNA5 (SEQ ID NO: 53)

TTGATTAAAGAGGTTGGTGGT

Nucleotide sequence of sasgRNA for mouse KCNA1; sgRNA5 (SEQ ID NO: 54)

GAATTTAACTAGCTGTATCCC

Nucleotide sequence of sasgRNA for mouse KCNA1; sgRNA7 (SEQ ID NO: 55)

TACTAGCCACAATAGAGCCAG pAAV-CMV-sadCas9-U6gRNA(Kcna 1-sa sgRNA1) used in in vitro qPCR experiments (SEQ ID NO: 56)

CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCGTCGGGCGACC TTTGGTCGCCCGGCC

TCAGTGAGCGAGCGAGCGCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCC TGCGGCCTCTAGACTC

GAGGCGTTGACATTGATTATTGACTAGTTATTAATAGTAATCAATTACGGGGTCATT AGTTCATAGCCCATATATG

GAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGAC CCCCGCCCATTGACGT

CAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAAT GGGTGGAGTATTTACGGT

AAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTG ACGTCAATGACGGTAAAT

GGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGT ACATCTACGTATTAGTCA

TCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAATGGGCGTGGATAGCGGT TTGACTCACGGGGATTT

CCAAGTCTCCACCCCATTGACGTCAATGGGAGTTTGTTTTGGCACCAAAATCAACGG GACTTTCCAAAATGTCGT

AACAACTCCGCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTAT ATAAGCAGAGCTCTCT

GGCTAACTACCGGTGCCACCATGGCCCCAAAGAAGAAGCGGAAGGTCGGTATCCACG GAGTCCCAGCAGCCAA

GCGGAACTACATCCTGGGCCTGGCCATCGGCATCACCAGCGTGGGCTACGGCATCAT CGACTACGAGACACGG

GACGTGATCGATGCCGGCGTGCGGCTGTTCAAAGAGGCCAACGTGGAAAACAACGAG GGCAGGCGGAGCAAG

AGAGGCGCCAGAAGGCTGAAGCGGCGGAGGCGGCATAGAATCCAGAGAGTGAAGAAG CTGCTGTTCGACTAC

AACCTGCTGACCGACCACAGCGAGCTGAGCGGCATCAACCCCTACGAGGCCAGAGTG AAGGGCCTGAGCCAG

AAGCTGAGCGAGGAAGAGTTCTCTGCCGCCCTGCTGCACCTGGCCAAGAGAAGAGGC GTGCACAACGTGAACG

AGGTGGAAGAGGACACCGGCAACGAGCTGTCCACCAAAGAGCAGATCAGCCGGAACA GCAAGGCCCTGGAAG

AGAAATACGTGGCCGAACTGCAGCTGGAACGGCTGAAGAAAGACGGCGAAGTGCGGG GCAGCATCAACAGATT

CAAGACCAGCGACTACGTGAAAGAAGCCAAACAGCTGCTGAAGGTGCAGAAGGCCTA CCACCAGCTGGACCAG

AGCTTCATCGACACCTACATCGACCTGCTGGAAACCCGGCGGACCTACTATGAGGGA CCTGGCGAGGGCAGCC

CCTTCGGCTGGAAGGACATCAAAGAATGGTACGAGATGCTGATGGGCCACTGCACCT ACTTCCCCGAGGAACT

GCGGAGCGTGAAGTACGCCTACAACGCCGACCTGTACAACGCCCTGAACGACCTGAA CAATCTCGTGATCACC

AGGGACGAGAACGAGAAGCTGGAATATTACGAGAAGTTCCAGATCATCGAGAACGTG TTCAAGCAGAAGAAGAA

GCCCACCCTGAAGCAGATCGCCAAAGAAATCCTCGTGAACGAAGAGGATATTAAGGG CTACAGAGTGACCAGCA

CCGGCAAGCCCGAGTTCACCAACCTGAAGGTGTACCACGACATCAAGGACATTACCG CCCGGAAAGAGATTATT

GAGAACGCCGAGCTGCTGGATCAGATTGCCAAGATCCTGACCATCTACCAGAGCAGC GAGGACATCCAGGAAG

AACTGACCAATCTGAACTCCGAGCTGACCCAGGAAGAGATCGAGCAGATCTCTAATC TGAAGGGCTATACCGGC

ACCCACAACCTGAGCCTGAAGGCCATCAACCTGATCCTGGACGAGCTGTGGCACACC AACGACAACCAGATCG

CTATCTTCAACCGGCTGAAGCTGGTGCCCAAGAAGGTGGACCTGTCCCAGCAGAAAG AGATCCCCACCACCCT

GGTGGACGACTTCATCCTGAGCCCCGTCGTGAAGAGAAGCTTCATCCAGAGCATCAA AGTGATCAACGCCATCA

TCAAGAAGTACGGCCTGCCCAACGACATCATTATCGAGCTGGCCCGCGAGAAGAACT CCAAGGACGCCCAGAA

AATGATCAACGAGATGCAGAAGCGGAACCGGCAGACCAACGAGCGGATCGAGGAAAT CATCCGGACCACCGGC AAAGAGAACGCCAAGTACCTGATCGAGAAGATCAAGCTGCACGACATGCAGGAAGGCAAG TGCCTGTACAGCC

TGGAAGCCATCCCTCTGGAAGATCTGCTGAACAACCCCTTCAACTATGAGGTGGACC ACATCATCCCCAGAAGC

GTGTCCTTCGACAACAGCTTCAACAACAAGGTGCTCGTGAAGCAGGAAGAAGCCAGC AAGAAGGGCAACCGGA

CCCCATTCCAGTACCTGAGCAGCAGCGACAGCAAGATCAGCTACGAAACCTTCAAGA AGCACATCCTGAATCTG

GCCAAGGGCAAGGGCAGAATCAGCAAGACCAAGAAAGAGTATCTGCTGGAAGAACGG GACATCAACAGGTTCT

CCGTGCAGAAAGACTTCATCAACCGGAACCTGGTGGATACCAGATACGCCACCAGAG GCCTGATGAACCTGCT

GCGGAGCTACTTCAGAGTGAACAACCTGGACGTGAAAGTGAAGTCCATCAATGGCGG CTTCACCAGCTTTCTGC

GGCGGAAGTGGAAGTTTAAGAAAGAGCGGAACAAGGGGTACAAGCACCACGCCGAGG ACGCCCTGATCATTGC

CAACGCCGATTTCATCTTCAAAGAGTGGAAGAAACTGGACAAGGCCAAAAAAGTGAT GGAAAACCAGATGTTCG

AGGAAAAGCAGGCCGAGAGCATGCCCGAGATCGAAACCGAGCAGGAGTACAAAGAGA TCTTCATCACCCCCCA

CCAGATCAAGCACATTAAGGACTTCAAGGACTACAAGTACAGCCACCGGGTGGACAA GAAGCCTAATAGAGAGC

TGATTAACGACACCCTGTACTCCACCCGGAAGGACGACAAGGGCAACACCCTGATCG TGAACAATCTGAACGGC

CTGTACGACAAGGACAATGACAAGCTGAAAAAGCTGATCAACAAGAGCCCCGAAAAG CTGCTGATGTACCACCA

CGACCCCCAGACCTACCAGAAACTGAAGCTGATTATGGAACAGTACGGCGACGAGAA GAATCCCCTGTACAAGT

ACTACGAGGAAACCGGGAACTACCTGACCAAGTACTCCAAAAAGGACAACGGCCCCG TGATCAAGAAGATTAAG

TATTACGGCAACAAACTGAACGCCCATCTGGACATCACCGACGACTACCCCAACAGC AGAAACAAGGTCGTGAA

GCTGTCCCTGAAGCCCTACAGATTCGACGTGTACCTGGACAATGGCGTGTACAAGTT CGTGACCGTGAAGAATC

TGGATGTGATCAAAAAAGAAAACTACTACGAAGTGAATAGCAAGTGCTATGAGGAAG CTAAGAAGCTGAAGAAGA

TCAGCAACCAGGCCGAGTTTATCGCCTCCTTCTACAACAACGATCTGATCAAGATCA ACGGCGAGCTGTATAGA

GTGATCGGCGTGAACAACGACCTGCTGAACCGGATCGAAGTGAACATGATCGACATC ACCTACCGCGAGTACCT

GGAAAACATGAACGACAAGAGGCCCCCCAGGATCATTAAGACAATCGCCTCCAAGAC CCAGAGCATTAAGAAGT

ACAGCACAGACATTCTGGGCAACCTGTATGAAGTGAAATCTAAGAAGCACCCTCAGA TCATCAAAAAGGGCAAAA

GGCCGGCGGCCACGAAAAAGGCCGGCCAGGCAAAAAAGAAAAAGGGATCCGGACGGG CTGACGCATTGGACG

ATTTTGATCTGGATATGCTGGGAAGTGACGCCCTCGATGATTTTGACCTTGACATGC TTGGTTCGGATGCCCTTG

ATGACTTTGACCTCGACATGCTCGGCAGTGACGCCCTTGATGATTTCGACCTGGACA TGCTGATTAACTGTACAG

GCAGTGGAGAGGGCAGAGGAAGTCTGCTAACATGCGGTGACGTCGAGGAGAATCCTG GCCCAATGGCCAAGC

CTTTGTCTCAAGAAGAATCCACCCTCATTGAAAGAGCAACGGCTACAATCAACAGCA TCCCCATCTCTGAAGACT

ACAGCGTCGCCAGCGCAGCTCTCTCTAGCGACGGCCGCATCTTCACTGGTGTCAATG TATATCATTTTACTGGG

GGACCTTGTGCAGAACTCGTGGTGCTGGGCACTGCTGCTGCTGCGGCAGCTGGCAAC CTGACTTGTATCGTCG

CGATCGGAAATGAGAACAGGGGCATCTTGAGCCCCTGCGGACGGTGCCGACAGGTGC TTCTCGATCTGCATCC

TGGGATCAAAGCCATAGTGAAGGACAGTGATGGACAGCCGACGGCAGTTGGGATTCG TGAATTGCTGCCCTCT

GGTTATGTGTGGGAGGGCTAAGAATTCCTAGAGCTCGCTGATCAGCCTCGACTGTGC CTTCTAGTTGCCAGCCA

TCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACT GTCCTTTCCTAATAAAAT

GAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTG GGGCAGGACAGCAAGG

GGGAGGATTGGGAAGAGAATAGCAGGCATGCTGGGGAGGTACCGAGGGCCTATTTCC CATGATTCCTTCATATT

TGCATATACGATACAAGGCTGTTAGAGAGATAATTGGAATTAATTTGACTGTAAACA CAAAGATATTAGTACAAAA

TACGTGACGTAGAAAGTAATAATTTCTTGGGTAGTTTGCAGTTTTAAAATTATGTTT TAAAATGGACTATCATATGC

TTACCGTAACTTGAAAGTATTTCGATTTCTTGGCTTTATATATCTTGTGGAAAGGAC GAAACACCGTACTAGCCAC

AATAGAGCCAGGTTTTAGTACTCTGGAAACAGAATCTACTAAAACAAGGCAAAATGC CGTGTTTATCTCGTCAACT

TGTTGGCGAGATTTTTGCGGCCGCAGGAACCCCTAGTGATGGAGTTGGCCACTCCCT CTCTGCGCGCTCGCTC

GCTCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGGGCTTTGCCCGGGCGGC CTCAGTGAGCGAGC

GAGCGCGCAGCTGCCTGCAGGGGCGCCTGATGCGGTATTTTCTCCTTACGCATCTGT GCGGTATTTCACACCG

CATACGTCAAAGCAACCATAGTACGCGCCCTGTAGCGGCGCATTAAGCGCGGCGGGT GTGGTGGTTACGCGCA

GCGTGACCGCTACACTTGCCAGCGCCTTAGCGCCCGCTCCTTTCGCTTTCTTCCCTT CCTTTCTCGCCACGTTC

GCCGGCTTTCCCCGTCAAGCTCTAAATCGGGGGCTCCCTTTAGGGTTCCGATTTAGT GCTTTACGGCACCTCGA

CCCCAAAAAACTTGATTTGGGTGATGGTTCACGTAGTGGGCCATCGCCCTGATAGAC GGTTTTTCGCCCTTTGAC

GTTGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAACTGGAACAACACTCAA CTCTATCTCGGGCTATTCT

TTTGATTTATAAGGGATTTTGCCGATTTCGGTCTATTGGTTAAAAAATGAGCTGATT TAACAAAAATTTAACGCGAA

TTTTAACAAAATATTAACGTTTACAATTTTATGGTGCACTCTCAGTACAATCTGCTC TGATGCCGCATAGTTAAGCC

AGCCCCGACACCCGCCAACACCCGCTGACGCGCCCTGACGGGCTTGTCTGCTCCCGG CATCCGCTTACAGACA

AGCTGTGACCGTCTCCGGGAGCTGCATGTGTCAGAGGTTTTCACCGTCATCACCGAA ACGCGCGAGACGAAAG

GGCCTCGTGATACGCCTATTTTTATAGGTTAATGTCATGATAATAATGGTTTCTTAG ACGTCAGGTGGCACTTTTC

GGGGAAATGTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGT ATCCGCTCATGAGACAATA ACCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTCCG TGTCGCCCTTATTCCC

TTTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTA AAAGATGCTGAAGATCAGT

TGGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGA GTTTTCGCCCCGAAGAA

CGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGT ATTGACGCCGGGCAAGAG

CAACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTC ACAGAAAAGCATCTTACG

GATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACT GCGGCCAACTTACTTCTG

ACAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCAT GTAACTCGCCTTGATCG

TTGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCC TGTAGCAATGGCAACA

ACGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTA ATAGACTGGATGGAGGCG

GATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCT GATAAATCTGGAGCCGG

TGAGCGTGGAAGCCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCG TATCGTAGTTATCTACA

CGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTG CCTCACTGATTAAGCAT

TGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCAT TTTTAATTTAAAAGGATCTAG

GTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTC CACTGAGCGTCAGACCCC

GTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGC TTGCAAACAAAAAAACCAC

CGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGG TAACTGGCTTCAGCAGA

GCGCAGATACCAAATACTGTTCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAG AACTCTGTAGCACCGCCT

ACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCG TGTCTTACCGGGTTGGA

CTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTG CACACAGCCCAGCTTG

GAGCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCC ACGCTTCCCGAAGGGA

GAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGG AGCTTCCAGGGGGA

AACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGA TTTTTGTGATGCTCGTCA

GGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCC TTTTGCTGGCCTTTTG CTCACATGT pAAV-CMV-sadCas9-U6gRNA(Kcna 1-sa sgRNA2) used in in vitro qPCR experiments (SEQ ID NO: 57)

CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCGTCGGGCGACC TTTGGTCGCCCGGCC

TCAGTGAGCGAGCGAGCGCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCC TGCGGCCTCTAGACTC

GAGGCGTTGACATTGATTATTGACTAGTTATTAATAGTAATCAATTACGGGGTCATT AGTTCATAGCCCATATATG

GAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGAC CCCCGCCCATTGACGT

CAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAAT GGGTGGAGTATTTACGGT

AAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTG ACGTCAATGACGGTAAAT

GGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGT ACATCTACGTATTAGTCA

TCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAATGGGCGTGGATAGCGGT TTGACTCACGGGGATTT

CCAAGTCTCCACCCCATTGACGTCAATGGGAGTTTGTTTTGGCACCAAAATCAACGG GACTTTCCAAAATGTCGT

AACAACTCCGCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTAT ATAAGCAGAGCTCTCT

GGCTAACTACCGGTGCCACCATGGCCCCAAAGAAGAAGCGGAAGGTCGGTATCCACG GAGTCCCAGCAGCCAA

GCGGAACTACATCCTGGGCCTGGCCATCGGCATCACCAGCGTGGGCTACGGCATCAT CGACTACGAGACACGG

GACGTGATCGATGCCGGCGTGCGGCTGTTCAAAGAGGCCAACGTGGAAAACAACGAG GGCAGGCGGAGCAAG

AGAGGCGCCAGAAGGCTGAAGCGGCGGAGGCGGCATAGAATCCAGAGAGTGAAGAAG CTGCTGTTCGACTAC

AACCTGCTGACCGACCACAGCGAGCTGAGCGGCATCAACCCCTACGAGGCCAGAGTG AAGGGCCTGAGCCAG

AAGCTGAGCGAGGAAGAGTTCTCTGCCGCCCTGCTGCACCTGGCCAAGAGAAGAGGC GTGCACAACGTGAACG

AGGTGGAAGAGGACACCGGCAACGAGCTGTCCACCAAAGAGCAGATCAGCCGGAACA GCAAGGCCCTGGAAG

AGAAATACGTGGCCGAACTGCAGCTGGAACGGCTGAAGAAAGACGGCGAAGTGCGGG GCAGCATCAACAGATT

CAAGACCAGCGACTACGTGAAAGAAGCCAAACAGCTGCTGAAGGTGCAGAAGGCCTA CCACCAGCTGGACCAG

AGCTTCATCGACACCTACATCGACCTGCTGGAAACCCGGCGGACCTACTATGAGGGA CCTGGCGAGGGCAGCC

CCTTCGGCTGGAAGGACATCAAAGAATGGTACGAGATGCTGATGGGCCACTGCACCT ACTTCCCCGAGGAACT

GCGGAGCGTGAAGTACGCCTACAACGCCGACCTGTACAACGCCCTGAACGACCTGAA CAATCTCGTGATCACC

AGGGACGAGAACGAGAAGCTGGAATATTACGAGAAGTTCCAGATCATCGAGAACGTG TTCAAGCAGAAGAAGAA

GCCCACCCTGAAGCAGATCGCCAAAGAAATCCTCGTGAACGAAGAGGATATTAAGGG CTACAGAGTGACCAGCA

CCGGCAAGCCCGAGTTCACCAACCTGAAGGTGTACCACGACATCAAGGACATTACCG CCCGGAAAGAGATTATT

GAGAACGCCGAGCTGCTGGATCAGATTGCCAAGATCCTGACCATCTACCAGAGCAGC GAGGACATCCAGGAAG

AACTGACCAATCTGAACTCCGAGCTGACCCAGGAAGAGATCGAGCAGATCTCTAATC TGAAGGGCTATACCGGC ACCCACAACCTGAGCCTGAAGGCCATCAACCTGATCCTGGACGAGCTGTGGCACACCAAC GACAACCAGATCG

CTATCTTCAACCGGCTGAAGCTGGTGCCCAAGAAGGTGGACCTGTCCCAGCAGAAAG AGATCCCCACCACCCT

GGTGGACGACTTCATCCTGAGCCCCGTCGTGAAGAGAAGCTTCATCCAGAGCATCAA AGTGATCAACGCCATCA

TCAAGAAGTACGGCCTGCCCAACGACATCATTATCGAGCTGGCCCGCGAGAAGAACT CCAAGGACGCCCAGAA

AATGATCAACGAGATGCAGAAGCGGAACCGGCAGACCAACGAGCGGATCGAGGAAAT CATCCGGACCACCGGC

AAAGAGAACGCCAAGTACCTGATCGAGAAGATCAAGCTGCACGACATGCAGGAAGGC AAGTGCCTGTACAGCC

TGGAAGCCATCCCTCTGGAAGATCTGCTGAACAACCCCTTCAACTATGAGGTGGACC ACATCATCCCCAGAAGC

GTGTCCTTCGACAACAGCTTCAACAACAAGGTGCTCGTGAAGCAGGAAGAAGCCAGC AAGAAGGGCAACCGGA

CCCCATTCCAGTACCTGAGCAGCAGCGACAGCAAGATCAGCTACGAAACCTTCAAGA AGCACATCCTGAATCTG

GCCAAGGGCAAGGGCAGAATCAGCAAGACCAAGAAAGAGTATCTGCTGGAAGAACGG GACATCAACAGGTTCT

CCGTGCAGAAAGACTTCATCAACCGGAACCTGGTGGATACCAGATACGCCACCAGAG GCCTGATGAACCTGCT

GCGGAGCTACTTCAGAGTGAACAACCTGGACGTGAAAGTGAAGTCCATCAATGGCGG CTTCACCAGCTTTCTGC

GGCGGAAGTGGAAGTTTAAGAAAGAGCGGAACAAGGGGTACAAGCACCACGCCGAGG ACGCCCTGATCATTGC

CAACGCCGATTTCATCTTCAAAGAGTGGAAGAAACTGGACAAGGCCAAAAAAGTGAT GGAAAACCAGATGTTCG

AGGAAAAGCAGGCCGAGAGCATGCCCGAGATCGAAACCGAGCAGGAGTACAAAGAGA TCTTCATCACCCCCCA

CCAGATCAAGCACATTAAGGACTTCAAGGACTACAAGTACAGCCACCGGGTGGACAA GAAGCCTAATAGAGAGC

TGATTAACGACACCCTGTACTCCACCCGGAAGGACGACAAGGGCAACACCCTGATCG TGAACAATCTGAACGGC

CTGTACGACAAGGACAATGACAAGCTGAAAAAGCTGATCAACAAGAGCCCCGAAAAG CTGCTGATGTACCACCA

CGACCCCCAGACCTACCAGAAACTGAAGCTGATTATGGAACAGTACGGCGACGAGAA GAATCCCCTGTACAAGT

ACTACGAGGAAACCGGGAACTACCTGACCAAGTACTCCAAAAAGGACAACGGCCCCG TGATCAAGAAGATTAAG

TATTACGGCAACAAACTGAACGCCCATCTGGACATCACCGACGACTACCCCAACAGC AGAAACAAGGTCGTGAA

GCTGTCCCTGAAGCCCTACAGATTCGACGTGTACCTGGACAATGGCGTGTACAAGTT CGTGACCGTGAAGAATC

TGGATGTGATCAAAAAAGAAAACTACTACGAAGTGAATAGCAAGTGCTATGAGGAAG CTAAGAAGCTGAAGAAGA

TCAGCAACCAGGCCGAGTTTATCGCCTCCTTCTACAACAACGATCTGATCAAGATCA ACGGCGAGCTGTATAGA

GTGATCGGCGTGAACAACGACCTGCTGAACCGGATCGAAGTGAACATGATCGACATC ACCTACCGCGAGTACCT

GGAAAACATGAACGACAAGAGGCCCCCCAGGATCATTAAGACAATCGCCTCCAAGAC CCAGAGCATTAAGAAGT

ACAGCACAGACATTCTGGGCAACCTGTATGAAGTGAAATCTAAGAAGCACCCTCAGA TCATCAAAAAGGGCAAAA

GGCCGGCGGCCACGAAAAAGGCCGGCCAGGCAAAAAAGAAAAAGGGATCCGGACGGG CTGACGCATTGGACG

ATTTTGATCTGGATATGCTGGGAAGTGACGCCCTCGATGATTTTGACCTTGACATGC TTGGTTCGGATGCCCTTG

ATGACTTTGACCTCGACATGCTCGGCAGTGACGCCCTTGATGATTTCGACCTGGACA TGCTGATTAACTGTACAG

GCAGTGGAGAGGGCAGAGGAAGTCTGCTAACATGCGGTGACGTCGAGGAGAATCCTG GCCCAATGGCCAAGC

CTTTGTCTCAAGAAGAATCCACCCTCATTGAAAGAGCAACGGCTACAATCAACAGCA TCCCCATCTCTGAAGACT

ACAGCGTCGCCAGCGCAGCTCTCTCTAGCGACGGCCGCATCTTCACTGGTGTCAATG TATATCATTTTACTGGG

GGACCTTGTGCAGAACTCGTGGTGCTGGGCACTGCTGCTGCTGCGGCAGCTGGCAAC CTGACTTGTATCGTCG

CGATCGGAAATGAGAACAGGGGCATCTTGAGCCCCTGCGGACGGTGCCGACAGGTGC TTCTCGATCTGCATCC

TGGGATCAAAGCCATAGTGAAGGACAGTGATGGACAGCCGACGGCAGTTGGGATTCG TGAATTGCTGCCCTCT

GGTTATGTGTGGGAGGGCTAAGAATTCCTAGAGCTCGCTGATCAGCCTCGACTGTGC CTTCTAGTTGCCAGCCA

TCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACT GTCCTTTCCTAATAAAAT

GAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTG GGGCAGGACAGCAAGG

GGGAGGATTGGGAAGAGAATAGCAGGCATGCTGGGGAGGTACCGAGGGCCTATTTCC CATGATTCCTTCATATT

TGCATATACGATACAAGGCTGTTAGAGAGATAATTGGAATTAATTTGACTGTAAACA CAAAGATATTAGTACAAAA

TACGTGACGTAGAAAGTAATAATTTCTTGGGTAGTTTGCAGTTTTAAAATTATGTTT TAAAATGGACTATCATATGC

TTACCGTAACTTGAAAGTATTTCGATTTCTTGGCTTTATATATCTTGTGGAAAGGAC GAAAcaccgCCTTACTAGCC

ACAATAGAGCgTTTTAGTACTCTGGAAACAGAATCTACTAAAACAAGGCAAAATGCC GTGTTTATCTCGTCAACTT

GTTGGCGAGATTTTTGCGGCCGCAGGAACCCCTAGTGATGGAGTTGGCCACTCCCTC TCTGCGCGCTCGCTCG

CTCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGGGCTTTGCCCGGGCGGCC TCAGTGAGCGAGCG

AGCGCGCAGCTGCCTGCAGGGGCGCCTGATGCGGTATTTTCTCCTTACGCATCTGTG CGGTATTTCACACCGCA

TACGTCAAAGCAACCATAGTACGCGCCCTGTAGCGGCGCATTAAGCGCGGCGGGTGT GGTGGTTACGCGCAGC

GTGACCGCTACACTTGCCAGCGCCTTAGCGCCCGCTCCTTTCGCTTTCTTCCCTTCC TTTCTCGCCACGTTCGC

CGGCTTTCCCCGTCAAGCTCTAAATCGGGGGCTCCCTTTAGGGTTCCGATTTAGTGC TTTACGGCACCTCGACC

CCAAAAAACTTGATTTGGGTGATGGTTCACGTAGTGGGCCATCGCCCTGATAGACGG TTTTTCGCCCTTTGACGT

TGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAACTGGAACAACACTCAACT CTATCTCGGGCTATTCTTT

TGATTTATAAGGGATTTTGCCGATTTCGGTCTATTGGTTAAAAAATGAGCTGATTTA ACAAAAATTTAACGCGAATT TTAACAAAATATTAACGTTTACAATTTTATGGTGCACTCTCAGTACAATCTGCTCTGATG CCGCATAGTTAAGCCA

GCCCCGACACCCGCCAACACCCGCTGACGCGCCCTGACGGGCTTGTCTGCTCCCGGC ATCCGCTTACAGACAA

GCTGTGACCGTCTCCGGGAGCTGCATGTGTCAGAGGTTTTCACCGTCATCACCGAAA CGCGCGAGACGAAAGG

GCCTCGTGATACGCCTATTTTTATAGGTTAATGTCATGATAATAATGGTTTCTTAGA CGTCAGGTGGCACTTTTCG

GGGAAATGTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTA TCCGCTCATGAGACAATAA

CCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTC CGTGTCGCCCTTATTCCCT

TTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAA AAGATGCTGAAGATCAGTT

GGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAG TTTTCGCCCCGAAGAAC

GTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTA TTGACGCCGGGCAAGAGC

AACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCA CAGAAAAGCATCTTACGG

ATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTG CGGCCAACTTACTTCTGA

CAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATG TAACTCGCCTTGATCGT

TGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCT GTAGCAATGGCAACAA

CGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAA TAGACTGGATGGAGGCG

GATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCT GATAAATCTGGAGCCGG

TGAGCGTGGAAGCCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCG TATCGTAGTTATCTACA

CGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTG CCTCACTGATTAAGCAT

TGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCAT TTTTAATTTAAAAGGATCTAG

GTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTC CACTGAGCGTCAGACCCC

GTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGC TTGCAAACAAAAAAACCAC

CGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGG TAACTGGCTTCAGCAGA

GCGCAGATACCAAATACTGTTCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAG AACTCTGTAGCACCGCCT

ACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCG TGTCTTACCGGGTTGGA

CTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTG CACACAGCCCAGCTTG

GAGCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCC ACGCTTCCCGAAGGGA

GAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGG AGCTTCCAGGGGGA

AACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGA TTTTTGTGATGCTCGTCA

GGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCC TTTTGCTGGCCTTTTG CTCACATGT pAAV-CMV-sadCas9-U6gRNA(Kcna 1-sa sgRNA3) used in in vitro qPCR experiments (SEQ ID NO: 58)

CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCGTCGGGCGACC TTTGGTCGCCCGGCC

TCAGTGAGCGAGCGAGCGCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCC TGCGGCCTCTAGACTC

GAGGCGTTGACATTGATTATTGACTAGTTATTAATAGTAATCAATTACGGGGTCATT AGTTCATAGCCCATATATG

GAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGAC CCCCGCCCATTGACGT

CAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAAT GGGTGGAGTATTTACGGT

AAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTG ACGTCAATGACGGTAAAT

GGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGT ACATCTACGTATTAGTCA

TCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAATGGGCGTGGATAGCGGT TTGACTCACGGGGATTT

CCAAGTCTCCACCCCATTGACGTCAATGGGAGTTTGTTTTGGCACCAAAATCAACGG GACTTTCCAAAATGTCGT

AACAACTCCGCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTAT ATAAGCAGAGCTCTCT

GGCTAACTACCGGTGCCACCATGGCCCCAAAGAAGAAGCGGAAGGTCGGTATCCACG GAGTCCCAGCAGCCAA

GCGGAACTACATCCTGGGCCTGGCCATCGGCATCACCAGCGTGGGCTACGGCATCAT CGACTACGAGACACGG

GACGTGATCGATGCCGGCGTGCGGCTGTTCAAAGAGGCCAACGTGGAAAACAACGAG GGCAGGCGGAGCAAG

AGAGGCGCCAGAAGGCTGAAGCGGCGGAGGCGGCATAGAATCCAGAGAGTGAAGAAG CTGCTGTTCGACTAC

AACCTGCTGACCGACCACAGCGAGCTGAGCGGCATCAACCCCTACGAGGCCAGAGTG AAGGGCCTGAGCCAG

AAGCTGAGCGAGGAAGAGTTCTCTGCCGCCCTGCTGCACCTGGCCAAGAGAAGAGGC GTGCACAACGTGAACG

AGGTGGAAGAGGACACCGGCAACGAGCTGTCCACCAAAGAGCAGATCAGCCGGAACA GCAAGGCCCTGGAAG

AGAAATACGTGGCCGAACTGCAGCTGGAACGGCTGAAGAAAGACGGCGAAGTGCGGG GCAGCATCAACAGATT

CAAGACCAGCGACTACGTGAAAGAAGCCAAACAGCTGCTGAAGGTGCAGAAGGCCTA CCACCAGCTGGACCAG

AGCTTCATCGACACCTACATCGACCTGCTGGAAACCCGGCGGACCTACTATGAGGGA CCTGGCGAGGGCAGCC

CCTTCGGCTGGAAGGACATCAAAGAATGGTACGAGATGCTGATGGGCCACTGCACCT ACTTCCCCGAGGAACT

GCGGAGCGTGAAGTACGCCTACAACGCCGACCTGTACAACGCCCTGAACGACCTGAA CAATCTCGTGATCACC AGGGACGAGAACGAGAAGCTGGAATATTACGAGAAGTTCCAGATCATCGAGAACGTGTTC AAGCAGAAGAAGAA

GCCCACCCTGAAGCAGATCGCCAAAGAAATCCTCGTGAACGAAGAGGATATTAAGGG CTACAGAGTGACCAGCA

CCGGCAAGCCCGAGTTCACCAACCTGAAGGTGTACCACGACATCAAGGACATTACCG CCCGGAAAGAGATTATT

GAGAACGCCGAGCTGCTGGATCAGATTGCCAAGATCCTGACCATCTACCAGAGCAGC GAGGACATCCAGGAAG

AACTGACCAATCTGAACTCCGAGCTGACCCAGGAAGAGATCGAGCAGATCTCTAATC TGAAGGGCTATACCGGC

ACCCACAACCTGAGCCTGAAGGCCATCAACCTGATCCTGGACGAGCTGTGGCACACC AACGACAACCAGATCG

CTATCTTCAACCGGCTGAAGCTGGTGCCCAAGAAGGTGGACCTGTCCCAGCAGAAAG AGATCCCCACCACCCT

GGTGGACGACTTCATCCTGAGCCCCGTCGTGAAGAGAAGCTTCATCCAGAGCATCAA AGTGATCAACGCCATCA

TCAAGAAGTACGGCCTGCCCAACGACATCATTATCGAGCTGGCCCGCGAGAAGAACT CCAAGGACGCCCAGAA

AATGATCAACGAGATGCAGAAGCGGAACCGGCAGACCAACGAGCGGATCGAGGAAAT CATCCGGACCACCGGC

AAAGAGAACGCCAAGTACCTGATCGAGAAGATCAAGCTGCACGACATGCAGGAAGGC AAGTGCCTGTACAGCC

TGGAAGCCATCCCTCTGGAAGATCTGCTGAACAACCCCTTCAACTATGAGGTGGACC ACATCATCCCCAGAAGC

GTGTCCTTCGACAACAGCTTCAACAACAAGGTGCTCGTGAAGCAGGAAGAAGCCAGC AAGAAGGGCAACCGGA

CCCCATTCCAGTACCTGAGCAGCAGCGACAGCAAGATCAGCTACGAAACCTTCAAGA AGCACATCCTGAATCTG

GCCAAGGGCAAGGGCAGAATCAGCAAGACCAAGAAAGAGTATCTGCTGGAAGAACGG GACATCAACAGGTTCT

CCGTGCAGAAAGACTTCATCAACCGGAACCTGGTGGATACCAGATACGCCACCAGAG GCCTGATGAACCTGCT

GCGGAGCTACTTCAGAGTGAACAACCTGGACGTGAAAGTGAAGTCCATCAATGGCGG CTTCACCAGCTTTCTGC

GGCGGAAGTGGAAGTTTAAGAAAGAGCGGAACAAGGGGTACAAGCACCACGCCGAGG ACGCCCTGATCATTGC

CAACGCCGATTTCATCTTCAAAGAGTGGAAGAAACTGGACAAGGCCAAAAAAGTGAT GGAAAACCAGATGTTCG

AGGAAAAGCAGGCCGAGAGCATGCCCGAGATCGAAACCGAGCAGGAGTACAAAGAGA TCTTCATCACCCCCCA

CCAGATCAAGCACATTAAGGACTTCAAGGACTACAAGTACAGCCACCGGGTGGACAA GAAGCCTAATAGAGAGC

TGATTAACGACACCCTGTACTCCACCCGGAAGGACGACAAGGGCAACACCCTGATCG TGAACAATCTGAACGGC

CTGTACGACAAGGACAATGACAAGCTGAAAAAGCTGATCAACAAGAGCCCCGAAAAG CTGCTGATGTACCACCA

CGACCCCCAGACCTACCAGAAACTGAAGCTGATTATGGAACAGTACGGCGACGAGAA GAATCCCCTGTACAAGT

ACTACGAGGAAACCGGGAACTACCTGACCAAGTACTCCAAAAAGGACAACGGCCCCG TGATCAAGAAGATTAAG

TATTACGGCAACAAACTGAACGCCCATCTGGACATCACCGACGACTACCCCAACAGC AGAAACAAGGTCGTGAA

GCTGTCCCTGAAGCCCTACAGATTCGACGTGTACCTGGACAATGGCGTGTACAAGTT CGTGACCGTGAAGAATC

TGGATGTGATCAAAAAAGAAAACTACTACGAAGTGAATAGCAAGTGCTATGAGGAAG CTAAGAAGCTGAAGAAGA

TCAGCAACCAGGCCGAGTTTATCGCCTCCTTCTACAACAACGATCTGATCAAGATCA ACGGCGAGCTGTATAGA

GTGATCGGCGTGAACAACGACCTGCTGAACCGGATCGAAGTGAACATGATCGACATC ACCTACCGCGAGTACCT

GGAAAACATGAACGACAAGAGGCCCCCCAGGATCATTAAGACAATCGCCTCCAAGAC CCAGAGCATTAAGAAGT

ACAGCACAGACATTCTGGGCAACCTGTATGAAGTGAAATCTAAGAAGCACCCTCAGA TCATCAAAAAGGGCAAAA

GGCCGGCGGCCACGAAAAAGGCCGGCCAGGCAAAAAAGAAAAAGGGATCCGGACGGG CTGACGCATTGGACG

ATTTTGATCTGGATATGCTGGGAAGTGACGCCCTCGATGATTTTGACCTTGACATGC TTGGTTCGGATGCCCTTG

ATGACTTTGACCTCGACATGCTCGGCAGTGACGCCCTTGATGATTTCGACCTGGACA TGCTGATTAACTGTACAG

GCAGTGGAGAGGGCAGAGGAAGTCTGCTAACATGCGGTGACGTCGAGGAGAATCCTG GCCCAATGGCCAAGC

CTTTGTCTCAAGAAGAATCCACCCTCATTGAAAGAGCAACGGCTACAATCAACAGCA TCCCCATCTCTGAAGACT

ACAGCGTCGCCAGCGCAGCTCTCTCTAGCGACGGCCGCATCTTCACTGGTGTCAATG TATATCATTTTACTGGG

GGACCTTGTGCAGAACTCGTGGTGCTGGGCACTGCTGCTGCTGCGGCAGCTGGCAAC CTGACTTGTATCGTCG

CGATCGGAAATGAGAACAGGGGCATCTTGAGCCCCTGCGGACGGTGCCGACAGGTGC TTCTCGATCTGCATCC

TGGGATCAAAGCCATAGTGAAGGACAGTGATGGACAGCCGACGGCAGTTGGGATTCG TGAATTGCTGCCCTCT

GGTTATGTGTGGGAGGGCTAAGAATTCCTAGAGCTCGCTGATCAGCCTCGACTGTGC CTTCTAGTTGCCAGCCA

TCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACT GTCCTTTCCTAATAAAAT

GAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTG GGGCAGGACAGCAAGG

GGGAGGATTGGGAAGAGAATAGCAGGCATGCTGGGGAGGTACCGAGGGCCTATTTCC CATGATTCCTTCATATT

TGCATATACGATACAAGGCTGTTAGAGAGATAATTGGAATTAATTTGACTGTAAACA CAAAGATATTAGTACAAAA

TACGTGACGTAGAAAGTAATAATTTCTTGGGTAGTTTGCAGTTTTAAAATTATGTTT TAAAATGGACTATCATATGC

TTACCGTAACTTGAAAGTATTTCGATTTCTTGGCTTTATATATCTTGTGGAAAGGAC GAAAcaccgTGTGATCATTGA

CTTTGATTAgTTTTAGTACTCTGGAAACAGAATCTACTAAAACAAGGCAAAATGCCG TGTTTATCTCGTCAACTTGT

TGGCGAGATTTTTGCGGCCGCAGGAACCCCTAGTGATGGAGTTGGCCACTCCCTCTC TGCGCGCTCGCTCGCT

CACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGGGCTTTGCCCGGGCGGCCTC AGTGAGCGAGCGAG

CGCGCAGCTGCCTGCAGGGGCGCCTGATGCGGTATTTTCTCCTTACGCATCTGTGCG GTATTTCACACCGCATA

CGTCAAAGCAACCATAGTACGCGCCCTGTAGCGGCGCATTAAGCGCGGCGGGTGTGG TGGTTACGCGCAGCGT GACCGCTACACTTGCCAGCGCCTTAGCGCCCGCTCCTTTCGCTTTCTTCCCTTCCTTTCT CGCCACGTTCGCCG

GCTTTCCCCGTCAAGCTCTAAATCGGGGGCTCCCTTTAGGGTTCCGATTTAGTGCTT TACGGCACCTCGACCCC

AAAAAACTTGATTTGGGTGATGGTTCACGTAGTGGGCCATCGCCCTGATAGACGGTT TTTCGCCCTTTGACGTTG

GAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAACTGGAACAACACTCAACTCT ATCTCGGGCTATTCTTTTG

ATTTATAAGGGATTTTGCCGATTTCGGTCTATTGGTTAAAAAATGAGCTGATTTAAC AAAAATTTAACGCGAATTTT

AACAAAATATTAACGTTTACAATTTTATGGTGCACTCTCAGTACAATCTGCTCTGAT GCCGCATAGTTAAGCCAGC

CCCGACACCCGCCAACACCCGCTGACGCGCCCTGACGGGCTTGTCTGCTCCCGGCAT CCGCTTACAGACAAGC

TGTGACCGTCTCCGGGAGCTGCATGTGTCAGAGGTTTTCACCGTCATCACCGAAACG CGCGAGACGAAAGGGC

CTCGTGATACGCCTATTTTTATAGGTTAATGTCATGATAATAATGGTTTCTTAGACG TCAGGTGGCACTTTTCGGG

GAAATGTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTATC CGCTCATGAGACAATAACC

CTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTCCG TGTCGCCCTTATTCCCTTTT

TTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAAAAG ATGCTGAAGATCAGTTGG

GTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAGTT TTCGCCCCGAAGAACGT

TTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTATT GACGCCGGGCAAGAGCAA

CTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCACA GAAAAGCATCTTACGGAT

GGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTGCG GCCAACTTACTTCTGACA

ACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATGTA ACTCGCCTTGATCGTTG

GGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCTGT AGCAATGGCAACAACG

TTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAATA GACTGGATGGAGGCGGAT

AAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCTGAT AAATCTGGAGCCGGTGA

GCGTGGAAGCCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCGTAT CGTAGTTATCTACACG

ACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTGCC TCACTGATTAAGCATTG

GTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCATTT TTAATTTAAAAGGATCTAGGT

GAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTCCA CTGAGCGTCAGACCCCGTA

GAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGCTTG CAAACAAAAAAACCACCGC

TACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGGTAA CTGGCTTCAGCAGAGCG

CAGATACCAAATACTGTTCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAGAAC TCTGTAGCACCGCCTACA

TACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCGTGT CTTACCGGGTTGGACTC

AAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTGCAC ACAGCCCAGCTTGGA

GCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCCAC GCTTCCCGAAGGGAGA

AAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGGAG CTTCCAGGGGGAAAC

GCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGATTT TTGTGATGCTCGTCAGGG

GGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCCTTT TGCTGGCCTTTTGCTCA CATGT pAAV-CMV-sadCas9-U6gRNA(Kcna 1-sa sgRNA4) used in in vitro qPCR experiments (SEQ ID NO: 59)

CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCGTCGGGCGACC TTTGGTCGCCCGGCC

TCAGTGAGCGAGCGAGCGCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCC TGCGGCCTCTAGACTC

GAGGCGTTGACATTGATTATTGACTAGTTATTAATAGTAATCAATTACGGGGTCATT AGTTCATAGCCCATATATG

GAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGAC CCCCGCCCATTGACGT

CAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAAT GGGTGGAGTATTTACGGT

AAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTG ACGTCAATGACGGTAAAT

GGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGT ACATCTACGTATTAGTCA

TCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAATGGGCGTGGATAGCGGT TTGACTCACGGGGATTT

CCAAGTCTCCACCCCATTGACGTCAATGGGAGTTTGTTTTGGCACCAAAATCAACGG GACTTTCCAAAATGTCGT

AACAACTCCGCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTAT ATAAGCAGAGCTCTCT

GGCTAACTACCGGTGCCACCATGGCCCCAAAGAAGAAGCGGAAGGTCGGTATCCACG GAGTCCCAGCAGCCAA

GCGGAACTACATCCTGGGCCTGGCCATCGGCATCACCAGCGTGGGCTACGGCATCAT CGACTACGAGACACGG

GACGTGATCGATGCCGGCGTGCGGCTGTTCAAAGAGGCCAACGTGGAAAACAACGAG GGCAGGCGGAGCAAG

AGAGGCGCCAGAAGGCTGAAGCGGCGGAGGCGGCATAGAATCCAGAGAGTGAAGAAG CTGCTGTTCGACTAC

AACCTGCTGACCGACCACAGCGAGCTGAGCGGCATCAACCCCTACGAGGCCAGAGTG AAGGGCCTGAGCCAG

AAGCTGAGCGAGGAAGAGTTCTCTGCCGCCCTGCTGCACCTGGCCAAGAGAAGAGGC GTGCACAACGTGAACG

AGGTGGAAGAGGACACCGGCAACGAGCTGTCCACCAAAGAGCAGATCAGCCGGAACA GCAAGGCCCTGGAAG AGAAATACGTGGCCGAACTGCAGCTGGAACGGCTGAAGAAAGACGGCGAAGTGCGGGGCA GCATCAACAGATT

CAAGACCAGCGACTACGTGAAAGAAGCCAAACAGCTGCTGAAGGTGCAGAAGGCCTA CCACCAGCTGGACCAG

AGCTTCATCGACACCTACATCGACCTGCTGGAAACCCGGCGGACCTACTATGAGGGA CCTGGCGAGGGCAGCC

CCTTCGGCTGGAAGGACATCAAAGAATGGTACGAGATGCTGATGGGCCACTGCACCT ACTTCCCCGAGGAACT

GCGGAGCGTGAAGTACGCCTACAACGCCGACCTGTACAACGCCCTGAACGACCTGAA CAATCTCGTGATCACC

AGGGACGAGAACGAGAAGCTGGAATATTACGAGAAGTTCCAGATCATCGAGAACGTG TTCAAGCAGAAGAAGAA

GCCCACCCTGAAGCAGATCGCCAAAGAAATCCTCGTGAACGAAGAGGATATTAAGGG CTACAGAGTGACCAGCA

CCGGCAAGCCCGAGTTCACCAACCTGAAGGTGTACCACGACATCAAGGACATTACCG CCCGGAAAGAGATTATT

GAGAACGCCGAGCTGCTGGATCAGATTGCCAAGATCCTGACCATCTACCAGAGCAGC GAGGACATCCAGGAAG

AACTGACCAATCTGAACTCCGAGCTGACCCAGGAAGAGATCGAGCAGATCTCTAATC TGAAGGGCTATACCGGC

ACCCACAACCTGAGCCTGAAGGCCATCAACCTGATCCTGGACGAGCTGTGGCACACC AACGACAACCAGATCG

CTATCTTCAACCGGCTGAAGCTGGTGCCCAAGAAGGTGGACCTGTCCCAGCAGAAAG AGATCCCCACCACCCT

GGTGGACGACTTCATCCTGAGCCCCGTCGTGAAGAGAAGCTTCATCCAGAGCATCAA AGTGATCAACGCCATCA

TCAAGAAGTACGGCCTGCCCAACGACATCATTATCGAGCTGGCCCGCGAGAAGAACT CCAAGGACGCCCAGAA

AATGATCAACGAGATGCAGAAGCGGAACCGGCAGACCAACGAGCGGATCGAGGAAAT CATCCGGACCACCGGC

AAAGAGAACGCCAAGTACCTGATCGAGAAGATCAAGCTGCACGACATGCAGGAAGGC AAGTGCCTGTACAGCC

TGGAAGCCATCCCTCTGGAAGATCTGCTGAACAACCCCTTCAACTATGAGGTGGACC ACATCATCCCCAGAAGC

GTGTCCTTCGACAACAGCTTCAACAACAAGGTGCTCGTGAAGCAGGAAGAAGCCAGC AAGAAGGGCAACCGGA

CCCCATTCCAGTACCTGAGCAGCAGCGACAGCAAGATCAGCTACGAAACCTTCAAGA AGCACATCCTGAATCTG

GCCAAGGGCAAGGGCAGAATCAGCAAGACCAAGAAAGAGTATCTGCTGGAAGAACGG GACATCAACAGGTTCT

CCGTGCAGAAAGACTTCATCAACCGGAACCTGGTGGATACCAGATACGCCACCAGAG GCCTGATGAACCTGCT

GCGGAGCTACTTCAGAGTGAACAACCTGGACGTGAAAGTGAAGTCCATCAATGGCGG CTTCACCAGCTTTCTGC

GGCGGAAGTGGAAGTTTAAGAAAGAGCGGAACAAGGGGTACAAGCACCACGCCGAGG ACGCCCTGATCATTGC

CAACGCCGATTTCATCTTCAAAGAGTGGAAGAAACTGGACAAGGCCAAAAAAGTGAT GGAAAACCAGATGTTCG

AGGAAAAGCAGGCCGAGAGCATGCCCGAGATCGAAACCGAGCAGGAGTACAAAGAGA TCTTCATCACCCCCCA

CCAGATCAAGCACATTAAGGACTTCAAGGACTACAAGTACAGCCACCGGGTGGACAA GAAGCCTAATAGAGAGC

TGATTAACGACACCCTGTACTCCACCCGGAAGGACGACAAGGGCAACACCCTGATCG TGAACAATCTGAACGGC

CTGTACGACAAGGACAATGACAAGCTGAAAAAGCTGATCAACAAGAGCCCCGAAAAG CTGCTGATGTACCACCA

CGACCCCCAGACCTACCAGAAACTGAAGCTGATTATGGAACAGTACGGCGACGAGAA GAATCCCCTGTACAAGT

ACTACGAGGAAACCGGGAACTACCTGACCAAGTACTCCAAAAAGGACAACGGCCCCG TGATCAAGAAGATTAAG

TATTACGGCAACAAACTGAACGCCCATCTGGACATCACCGACGACTACCCCAACAGC AGAAACAAGGTCGTGAA

GCTGTCCCTGAAGCCCTACAGATTCGACGTGTACCTGGACAATGGCGTGTACAAGTT CGTGACCGTGAAGAATC

TGGATGTGATCAAAAAAGAAAACTACTACGAAGTGAATAGCAAGTGCTATGAGGAAG CTAAGAAGCTGAAGAAGA

TCAGCAACCAGGCCGAGTTTATCGCCTCCTTCTACAACAACGATCTGATCAAGATCA ACGGCGAGCTGTATAGA

GTGATCGGCGTGAACAACGACCTGCTGAACCGGATCGAAGTGAACATGATCGACATC ACCTACCGCGAGTACCT

GGAAAACATGAACGACAAGAGGCCCCCCAGGATCATTAAGACAATCGCCTCCAAGAC CCAGAGCATTAAGAAGT

ACAGCACAGACATTCTGGGCAACCTGTATGAAGTGAAATCTAAGAAGCACCCTCAGA TCATCAAAAAGGGCAAAA

GGCCGGCGGCCACGAAAAAGGCCGGCCAGGCAAAAAAGAAAAAGGGATCCGGACGGG CTGACGCATTGGACG

ATTTTGATCTGGATATGCTGGGAAGTGACGCCCTCGATGATTTTGACCTTGACATGC TTGGTTCGGATGCCCTTG

ATGACTTTGACCTCGACATGCTCGGCAGTGACGCCCTTGATGATTTCGACCTGGACA TGCTGATTAACTGTACAG

GCAGTGGAGAGGGCAGAGGAAGTCTGCTAACATGCGGTGACGTCGAGGAGAATCCTG GCCCAATGGCCAAGC

CTTTGTCTCAAGAAGAATCCACCCTCATTGAAAGAGCAACGGCTACAATCAACAGCA TCCCCATCTCTGAAGACT

ACAGCGTCGCCAGCGCAGCTCTCTCTAGCGACGGCCGCATCTTCACTGGTGTCAATG TATATCATTTTACTGGG

GGACCTTGTGCAGAACTCGTGGTGCTGGGCACTGCTGCTGCTGCGGCAGCTGGCAAC CTGACTTGTATCGTCG

CGATCGGAAATGAGAACAGGGGCATCTTGAGCCCCTGCGGACGGTGCCGACAGGTGC TTCTCGATCTGCATCC

TGGGATCAAAGCCATAGTGAAGGACAGTGATGGACAGCCGACGGCAGTTGGGATTCG TGAATTGCTGCCCTCT

GGTTATGTGTGGGAGGGCTAAGAATTCCTAGAGCTCGCTGATCAGCCTCGACTGTGC CTTCTAGTTGCCAGCCA

TCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACT GTCCTTTCCTAATAAAAT

GAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTG GGGCAGGACAGCAAGG

GGGAGGATTGGGAAGAGAATAGCAGGCATGCTGGGGAGGTACCGAGGGCCTATTTCC CATGATTCCTTCATATT

TGCATATACGATACAAGGCTGTTAGAGAGATAATTGGAATTAATTTGACTGTAAACA CAAAGATATTAGTACAAAA

TACGTGACGTAGAAAGTAATAATTTCTTGGGTAGTTTGCAGTTTTAAAATTATGTTT TAAAATGGACTATCATATGC

TTACCGTAACTTGAAAGTATTTCGATTTCTTGGCTTTATATATCTTGTGGAAAGGAC GAAAcaccAGGGGCCTCTAG AAGGATCCCgTTTTAGTACTCTGGAAACAGAATCTACTAAAACAAGGCAAAATGCCGTGT TTATCTCGTCAACTTG

TTGGCGAGATTTTTGCGGCCGCAGGAACCCCTAGTGATGGAGTTGGCCACTCCCTCT CTGCGCGCTCGCTCGC

TCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGGGCTTTGCCCGGGCGGCCT CAGTGAGCGAGCGA

GCGCGCAGCTGCCTGCAGGGGCGCCTGATGCGGTATTTTCTCCTTACGCATCTGTGC GGTATTTCACACCGCAT

ACGTCAAAGCAACCATAGTACGCGCCCTGTAGCGGCGCATTAAGCGCGGCGGGTGTG GTGGTTACGCGCAGC

GTGACCGCTACACTTGCCAGCGCCTTAGCGCCCGCTCCTTTCGCTTTCTTCCCTTCC TTTCTCGCCACGTTCGC

CGGCTTTCCCCGTCAAGCTCTAAATCGGGGGCTCCCTTTAGGGTTCCGATTTAGTGC TTTACGGCACCTCGACC

CCAAAAAACTTGATTTGGGTGATGGTTCACGTAGTGGGCCATCGCCCTGATAGACGG TTTTTCGCCCTTTGACGT

TGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAACTGGAACAACACTCAACT CTATCTCGGGCTATTCTTT

TGATTTATAAGGGATTTTGCCGATTTCGGTCTATTGGTTAAAAAATGAGCTGATTTA ACAAAAATTTAACGCGAATT

TTAACAAAATATTAACGTTTACAATTTTATGGTGCACTCTCAGTACAATCTGCTCTG ATGCCGCATAGTTAAGCCA

GCCCCGACACCCGCCAACACCCGCTGACGCGCCCTGACGGGCTTGTCTGCTCCCGGC ATCCGCTTACAGACAA

GCTGTGACCGTCTCCGGGAGCTGCATGTGTCAGAGGTTTTCACCGTCATCACCGAAA CGCGCGAGACGAAAGG

GCCTCGTGATACGCCTATTTTTATAGGTTAATGTCATGATAATAATGGTTTCTTAGA CGTCAGGTGGCACTTTTCG

GGGAAATGTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTA TCCGCTCATGAGACAATAA

CCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTC CGTGTCGCCCTTATTCCCT

TTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAA AAGATGCTGAAGATCAGTT

GGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAG TTTTCGCCCCGAAGAAC

GTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTA TTGACGCCGGGCAAGAGC

AACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCA CAGAAAAGCATCTTACGG

ATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTG CGGCCAACTTACTTCTGA

CAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATG TAACTCGCCTTGATCGT

TGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCT GTAGCAATGGCAACAA

CGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAA TAGACTGGATGGAGGCG

GATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCT GATAAATCTGGAGCCGG

TGAGCGTGGAAGCCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCG TATCGTAGTTATCTACA

CGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTG CCTCACTGATTAAGCAT

TGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCAT TTTTAATTTAAAAGGATCTAG

GTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTC CACTGAGCGTCAGACCCC

GTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGC TTGCAAACAAAAAAACCAC

CGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGG TAACTGGCTTCAGCAGA

GCGCAGATACCAAATACTGTTCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAG AACTCTGTAGCACCGCCT

ACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCG TGTCTTACCGGGTTGGA

CTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTG CACACAGCCCAGCTTG

GAGCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCC ACGCTTCCCGAAGGGA

GAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGG AGCTTCCAGGGGGA

AACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGA TTTTTGTGATGCTCGTCA

GGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCC TTTTGCTGGCCTTTTG CTCACATGT pAAV-CMV-sadCas9-U6gRNA(Kcna 1-sa sgRNA5) used in in vitro qPCR experiments (SEQ ID NO: 60)

CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCGTCGGGCGACC TTTGGTCGCCCGGCC

TCAGTGAGCGAGCGAGCGCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCC TGCGGCCTCTAGACTC

GAGGCGTTGACATTGATTATTGACTAGTTATTAATAGTAATCAATTACGGGGTCATT AGTTCATAGCCCATATATG

GAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGAC CCCCGCCCATTGACGT

CAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAAT GGGTGGAGTATTTACGGT

AAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTG ACGTCAATGACGGTAAAT

GGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGT ACATCTACGTATTAGTCA

TCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAATGGGCGTGGATAGCGGT TTGACTCACGGGGATTT

CCAAGTCTCCACCCCATTGACGTCAATGGGAGTTTGTTTTGGCACCAAAATCAACGG GACTTTCCAAAATGTCGT

AACAACTCCGCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTAT ATAAGCAGAGCTCTCT

GGCTAACTACCGGTGCCACCATGGCCCCAAAGAAGAAGCGGAAGGTCGGTATCCACG GAGTCCCAGCAGCCAA

GCGGAACTACATCCTGGGCCTGGCCATCGGCATCACCAGCGTGGGCTACGGCATCAT CGACTACGAGACACGG GACGTGATCGATGCCGGCGTGCGGCTGTTCAAAGAGGCCAACGTGGAAAACAACGAGGGC AGGCGGAGCAAG

AGAGGCGCCAGAAGGCTGAAGCGGCGGAGGCGGCATAGAATCCAGAGAGTGAAGAAG CTGCTGTTCGACTAC

AACCTGCTGACCGACCACAGCGAGCTGAGCGGCATCAACCCCTACGAGGCCAGAGTG AAGGGCCTGAGCCAG

AAGCTGAGCGAGGAAGAGTTCTCTGCCGCCCTGCTGCACCTGGCCAAGAGAAGAGGC GTGCACAACGTGAACG

AGGTGGAAGAGGACACCGGCAACGAGCTGTCCACCAAAGAGCAGATCAGCCGGAACA GCAAGGCCCTGGAAG

AGAAATACGTGGCCGAACTGCAGCTGGAACGGCTGAAGAAAGACGGCGAAGTGCGGG GCAGCATCAACAGATT

CAAGACCAGCGACTACGTGAAAGAAGCCAAACAGCTGCTGAAGGTGCAGAAGGCCTA CCACCAGCTGGACCAG

AGCTTCATCGACACCTACATCGACCTGCTGGAAACCCGGCGGACCTACTATGAGGGA CCTGGCGAGGGCAGCC

CCTTCGGCTGGAAGGACATCAAAGAATGGTACGAGATGCTGATGGGCCACTGCACCT ACTTCCCCGAGGAACT

GCGGAGCGTGAAGTACGCCTACAACGCCGACCTGTACAACGCCCTGAACGACCTGAA CAATCTCGTGATCACC

AGGGACGAGAACGAGAAGCTGGAATATTACGAGAAGTTCCAGATCATCGAGAACGTG TTCAAGCAGAAGAAGAA

GCCCACCCTGAAGCAGATCGCCAAAGAAATCCTCGTGAACGAAGAGGATATTAAGGG CTACAGAGTGACCAGCA

CCGGCAAGCCCGAGTTCACCAACCTGAAGGTGTACCACGACATCAAGGACATTACCG CCCGGAAAGAGATTATT

GAGAACGCCGAGCTGCTGGATCAGATTGCCAAGATCCTGACCATCTACCAGAGCAGC GAGGACATCCAGGAAG

AACTGACCAATCTGAACTCCGAGCTGACCCAGGAAGAGATCGAGCAGATCTCTAATC TGAAGGGCTATACCGGC

ACCCACAACCTGAGCCTGAAGGCCATCAACCTGATCCTGGACGAGCTGTGGCACACC AACGACAACCAGATCG

CTATCTTCAACCGGCTGAAGCTGGTGCCCAAGAAGGTGGACCTGTCCCAGCAGAAAG AGATCCCCACCACCCT

GGTGGACGACTTCATCCTGAGCCCCGTCGTGAAGAGAAGCTTCATCCAGAGCATCAA AGTGATCAACGCCATCA

TCAAGAAGTACGGCCTGCCCAACGACATCATTATCGAGCTGGCCCGCGAGAAGAACT CCAAGGACGCCCAGAA

AATGATCAACGAGATGCAGAAGCGGAACCGGCAGACCAACGAGCGGATCGAGGAAAT CATCCGGACCACCGGC

AAAGAGAACGCCAAGTACCTGATCGAGAAGATCAAGCTGCACGACATGCAGGAAGGC AAGTGCCTGTACAGCC

TGGAAGCCATCCCTCTGGAAGATCTGCTGAACAACCCCTTCAACTATGAGGTGGACC ACATCATCCCCAGAAGC

GTGTCCTTCGACAACAGCTTCAACAACAAGGTGCTCGTGAAGCAGGAAGAAGCCAGC AAGAAGGGCAACCGGA

CCCCATTCCAGTACCTGAGCAGCAGCGACAGCAAGATCAGCTACGAAACCTTCAAGA AGCACATCCTGAATCTG

GCCAAGGGCAAGGGCAGAATCAGCAAGACCAAGAAAGAGTATCTGCTGGAAGAACGG GACATCAACAGGTTCT

CCGTGCAGAAAGACTTCATCAACCGGAACCTGGTGGATACCAGATACGCCACCAGAG GCCTGATGAACCTGCT

GCGGAGCTACTTCAGAGTGAACAACCTGGACGTGAAAGTGAAGTCCATCAATGGCGG CTTCACCAGCTTTCTGC

GGCGGAAGTGGAAGTTTAAGAAAGAGCGGAACAAGGGGTACAAGCACCACGCCGAGG ACGCCCTGATCATTGC

CAACGCCGATTTCATCTTCAAAGAGTGGAAGAAACTGGACAAGGCCAAAAAAGTGAT GGAAAACCAGATGTTCG

AGGAAAAGCAGGCCGAGAGCATGCCCGAGATCGAAACCGAGCAGGAGTACAAAGAGA TCTTCATCACCCCCCA

CCAGATCAAGCACATTAAGGACTTCAAGGACTACAAGTACAGCCACCGGGTGGACAA GAAGCCTAATAGAGAGC

TGATTAACGACACCCTGTACTCCACCCGGAAGGACGACAAGGGCAACACCCTGATCG TGAACAATCTGAACGGC

CTGTACGACAAGGACAATGACAAGCTGAAAAAGCTGATCAACAAGAGCCCCGAAAAG CTGCTGATGTACCACCA

CGACCCCCAGACCTACCAGAAACTGAAGCTGATTATGGAACAGTACGGCGACGAGAA GAATCCCCTGTACAAGT

ACTACGAGGAAACCGGGAACTACCTGACCAAGTACTCCAAAAAGGACAACGGCCCCG TGATCAAGAAGATTAAG

TATTACGGCAACAAACTGAACGCCCATCTGGACATCACCGACGACTACCCCAACAGC AGAAACAAGGTCGTGAA

GCTGTCCCTGAAGCCCTACAGATTCGACGTGTACCTGGACAATGGCGTGTACAAGTT CGTGACCGTGAAGAATC

TGGATGTGATCAAAAAAGAAAACTACTACGAAGTGAATAGCAAGTGCTATGAGGAAG CTAAGAAGCTGAAGAAGA

TCAGCAACCAGGCCGAGTTTATCGCCTCCTTCTACAACAACGATCTGATCAAGATCA ACGGCGAGCTGTATAGA

GTGATCGGCGTGAACAACGACCTGCTGAACCGGATCGAAGTGAACATGATCGACATC ACCTACCGCGAGTACCT

GGAAAACATGAACGACAAGAGGCCCCCCAGGATCATTAAGACAATCGCCTCCAAGAC CCAGAGCATTAAGAAGT

ACAGCACAGACATTCTGGGCAACCTGTATGAAGTGAAATCTAAGAAGCACCCTCAGA TCATCAAAAAGGGCAAAA

GGCCGGCGGCCACGAAAAAGGCCGGCCAGGCAAAAAAGAAAAAGGGATCCGGACGGG CTGACGCATTGGACG

ATTTTGATCTGGATATGCTGGGAAGTGACGCCCTCGATGATTTTGACCTTGACATGC TTGGTTCGGATGCCCTTG

ATGACTTTGACCTCGACATGCTCGGCAGTGACGCCCTTGATGATTTCGACCTGGACA TGCTGATTAACTGTACAG

GCAGTGGAGAGGGCAGAGGAAGTCTGCTAACATGCGGTGACGTCGAGGAGAATCCTG GCCCAATGGCCAAGC

CTTTGTCTCAAGAAGAATCCACCCTCATTGAAAGAGCAACGGCTACAATCAACAGCA TCCCCATCTCTGAAGACT

ACAGCGTCGCCAGCGCAGCTCTCTCTAGCGACGGCCGCATCTTCACTGGTGTCAATG TATATCATTTTACTGGG

GGACCTTGTGCAGAACTCGTGGTGCTGGGCACTGCTGCTGCTGCGGCAGCTGGCAAC CTGACTTGTATCGTCG

CGATCGGAAATGAGAACAGGGGCATCTTGAGCCCCTGCGGACGGTGCCGACAGGTGC TTCTCGATCTGCATCC

TGGGATCAAAGCCATAGTGAAGGACAGTGATGGACAGCCGACGGCAGTTGGGATTCG TGAATTGCTGCCCTCT

GGTTATGTGTGGGAGGGCTAAGAATTCCTAGAGCTCGCTGATCAGCCTCGACTGTGC CTTCTAGTTGCCAGCCA

TCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACT GTCCTTTCCTAATAAAAT GAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTGGGG CAGGACAGCAAGG

GGGAGGATTGGGAAGAGAATAGCAGGCATGCTGGGGAGGTACCGAGGGCCTATTTCC CATGATTCCTTCATATT

TGCATATACGATACAAGGCTGTTAGAGAGATAATTGGAATTAATTTGACTGTAAACA CAAAGATATTAGTACAAAA

TACGTGACGTAGAAAGTAATAATTTCTTGGGTAGTTTGCAGTTTTAAAATTATGTTT TAAAATGGACTATCATATGC

TTACCGTAACTTGAAAGTATTTCGATTTCTTGGCTTTATATATCTTGTGGAAAGGAC GAAAcaccTTGATTAAAGAG

GTTGGTGGTgTTTTAGTACTCTGGAAACAGAATCTACTAAAACAAGGCAAAATGCCG TGTTTATCTCGTCAACTTG

TTGGCGAGATTTTTGCGGCCGCAGGAACCCCTAGTGATGGAGTTGGCCACTCCCTCT CTGCGCGCTCGCTCGC

TCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGGGCTTTGCCCGGGCGGCCT CAGTGAGCGAGCGA

GCGCGCAGCTGCCTGCAGGGGCGCCTGATGCGGTATTTTCTCCTTACGCATCTGTGC GGTATTTCACACCGCAT

ACGTCAAAGCAACCATAGTACGCGCCCTGTAGCGGCGCATTAAGCGCGGCGGGTGTG GTGGTTACGCGCAGC

GTGACCGCTACACTTGCCAGCGCCTTAGCGCCCGCTCCTTTCGCTTTCTTCCCTTCC TTTCTCGCCACGTTCGC

CGGCTTTCCCCGTCAAGCTCTAAATCGGGGGCTCCCTTTAGGGTTCCGATTTAGTGC TTTACGGCACCTCGACC

CCAAAAAACTTGATTTGGGTGATGGTTCACGTAGTGGGCCATCGCCCTGATAGACGG TTTTTCGCCCTTTGACGT

TGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAACTGGAACAACACTCAACT CTATCTCGGGCTATTCTTT

TGATTTATAAGGGATTTTGCCGATTTCGGTCTATTGGTTAAAAAATGAGCTGATTTA ACAAAAATTTAACGCGAATT

TTAACAAAATATTAACGTTTACAATTTTATGGTGCACTCTCAGTACAATCTGCTCTG ATGCCGCATAGTTAAGCCA

GCCCCGACACCCGCCAACACCCGCTGACGCGCCCTGACGGGCTTGTCTGCTCCCGGC ATCCGCTTACAGACAA

GCTGTGACCGTCTCCGGGAGCTGCATGTGTCAGAGGTTTTCACCGTCATCACCGAAA CGCGCGAGACGAAAGG

GCCTCGTGATACGCCTATTTTTATAGGTTAATGTCATGATAATAATGGTTTCTTAGA CGTCAGGTGGCACTTTTCG

GGGAAATGTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTA TCCGCTCATGAGACAATAA

CCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTC CGTGTCGCCCTTATTCCCT

TTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAA AAGATGCTGAAGATCAGTT

GGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAG TTTTCGCCCCGAAGAAC

GTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTA TTGACGCCGGGCAAGAGC

AACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCA CAGAAAAGCATCTTACGG

ATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTG CGGCCAACTTACTTCTGA

CAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATG TAACTCGCCTTGATCGT

TGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCT GTAGCAATGGCAACAA

CGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAA TAGACTGGATGGAGGCG

GATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCT GATAAATCTGGAGCCGG

TGAGCGTGGAAGCCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCG TATCGTAGTTATCTACA

CGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTG CCTCACTGATTAAGCAT

TGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCAT TTTTAATTTAAAAGGATCTAG

GTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTC CACTGAGCGTCAGACCCC

GTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGC TTGCAAACAAAAAAACCAC

CGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGG TAACTGGCTTCAGCAGA

GCGCAGATACCAAATACTGTTCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAG AACTCTGTAGCACCGCCT

ACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCG TGTCTTACCGGGTTGGA

CTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTG CACACAGCCCAGCTTG

GAGCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCC ACGCTTCCCGAAGGGA

GAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGG AGCTTCCAGGGGGA

AACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGA TTTTTGTGATGCTCGTCA

GGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCC TTTTGCTGGCCTTTTG CTCACATGT pAAV-CMV-sadCas9-U6gRNA(Kcna 1-sa sgRNA6) used in in vitro qPCR experiments (SEQ ID NO: 61)

CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCGTCGGGCGACC TTTGGTCGCCCGGCC

TCAGTGAGCGAGCGAGCGCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCC TGCGGCCTCTAGACTC

GAGGCGTTGACATTGATTATTGACTAGTTATTAATAGTAATCAATTACGGGGTCATT AGTTCATAGCCCATATATG

GAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGAC CCCCGCCCATTGACGT

CAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAAT GGGTGGAGTATTTACGGT

AAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTG ACGTCAATGACGGTAAAT

GGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGT ACATCTACGTATTAGTCA TCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAATGGGCGTGGATAGCGGTTTG ACTCACGGGGATTT

CCAAGTCTCCACCCCATTGACGTCAATGGGAGTTTGTTTTGGCACCAAAATCAACGG GACTTTCCAAAATGTCGT

AACAACTCCGCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTAT ATAAGCAGAGCTCTCT

GGCTAACTACCGGTGCCACCATGGCCCCAAAGAAGAAGCGGAAGGTCGGTATCCACG GAGTCCCAGCAGCCAA

GCGGAACTACATCCTGGGCCTGGCCATCGGCATCACCAGCGTGGGCTACGGCATCAT CGACTACGAGACACGG

GACGTGATCGATGCCGGCGTGCGGCTGTTCAAAGAGGCCAACGTGGAAAACAACGAG GGCAGGCGGAGCAAG

AGAGGCGCCAGAAGGCTGAAGCGGCGGAGGCGGCATAGAATCCAGAGAGTGAAGAAG CTGCTGTTCGACTAC

AACCTGCTGACCGACCACAGCGAGCTGAGCGGCATCAACCCCTACGAGGCCAGAGTG AAGGGCCTGAGCCAG

AAGCTGAGCGAGGAAGAGTTCTCTGCCGCCCTGCTGCACCTGGCCAAGAGAAGAGGC GTGCACAACGTGAACG

AGGTGGAAGAGGACACCGGCAACGAGCTGTCCACCAAAGAGCAGATCAGCCGGAACA GCAAGGCCCTGGAAG

AGAAATACGTGGCCGAACTGCAGCTGGAACGGCTGAAGAAAGACGGCGAAGTGCGGG GCAGCATCAACAGATT

CAAGACCAGCGACTACGTGAAAGAAGCCAAACAGCTGCTGAAGGTGCAGAAGGCCTA CCACCAGCTGGACCAG

AGCTTCATCGACACCTACATCGACCTGCTGGAAACCCGGCGGACCTACTATGAGGGA CCTGGCGAGGGCAGCC

CCTTCGGCTGGAAGGACATCAAAGAATGGTACGAGATGCTGATGGGCCACTGCACCT ACTTCCCCGAGGAACT

GCGGAGCGTGAAGTACGCCTACAACGCCGACCTGTACAACGCCCTGAACGACCTGAA CAATCTCGTGATCACC

AGGGACGAGAACGAGAAGCTGGAATATTACGAGAAGTTCCAGATCATCGAGAACGTG TTCAAGCAGAAGAAGAA

GCCCACCCTGAAGCAGATCGCCAAAGAAATCCTCGTGAACGAAGAGGATATTAAGGG CTACAGAGTGACCAGCA

CCGGCAAGCCCGAGTTCACCAACCTGAAGGTGTACCACGACATCAAGGACATTACCG CCCGGAAAGAGATTATT

GAGAACGCCGAGCTGCTGGATCAGATTGCCAAGATCCTGACCATCTACCAGAGCAGC GAGGACATCCAGGAAG

AACTGACCAATCTGAACTCCGAGCTGACCCAGGAAGAGATCGAGCAGATCTCTAATC TGAAGGGCTATACCGGC

ACCCACAACCTGAGCCTGAAGGCCATCAACCTGATCCTGGACGAGCTGTGGCACACC AACGACAACCAGATCG

CTATCTTCAACCGGCTGAAGCTGGTGCCCAAGAAGGTGGACCTGTCCCAGCAGAAAG AGATCCCCACCACCCT

GGTGGACGACTTCATCCTGAGCCCCGTCGTGAAGAGAAGCTTCATCCAGAGCATCAA AGTGATCAACGCCATCA

TCAAGAAGTACGGCCTGCCCAACGACATCATTATCGAGCTGGCCCGCGAGAAGAACT CCAAGGACGCCCAGAA

AATGATCAACGAGATGCAGAAGCGGAACCGGCAGACCAACGAGCGGATCGAGGAAAT CATCCGGACCACCGGC

AAAGAGAACGCCAAGTACCTGATCGAGAAGATCAAGCTGCACGACATGCAGGAAGGC AAGTGCCTGTACAGCC

TGGAAGCCATCCCTCTGGAAGATCTGCTGAACAACCCCTTCAACTATGAGGTGGACC ACATCATCCCCAGAAGC

GTGTCCTTCGACAACAGCTTCAACAACAAGGTGCTCGTGAAGCAGGAAGAAGCCAGC AAGAAGGGCAACCGGA

CCCCATTCCAGTACCTGAGCAGCAGCGACAGCAAGATCAGCTACGAAACCTTCAAGA AGCACATCCTGAATCTG

GCCAAGGGCAAGGGCAGAATCAGCAAGACCAAGAAAGAGTATCTGCTGGAAGAACGG GACATCAACAGGTTCT

CCGTGCAGAAAGACTTCATCAACCGGAACCTGGTGGATACCAGATACGCCACCAGAG GCCTGATGAACCTGCT

GCGGAGCTACTTCAGAGTGAACAACCTGGACGTGAAAGTGAAGTCCATCAATGGCGG CTTCACCAGCTTTCTGC

GGCGGAAGTGGAAGTTTAAGAAAGAGCGGAACAAGGGGTACAAGCACCACGCCGAGG ACGCCCTGATCATTGC

CAACGCCGATTTCATCTTCAAAGAGTGGAAGAAACTGGACAAGGCCAAAAAAGTGAT GGAAAACCAGATGTTCG

AGGAAAAGCAGGCCGAGAGCATGCCCGAGATCGAAACCGAGCAGGAGTACAAAGAGA TCTTCATCACCCCCCA

CCAGATCAAGCACATTAAGGACTTCAAGGACTACAAGTACAGCCACCGGGTGGACAA GAAGCCTAATAGAGAGC

TGATTAACGACACCCTGTACTCCACCCGGAAGGACGACAAGGGCAACACCCTGATCG TGAACAATCTGAACGGC

CTGTACGACAAGGACAATGACAAGCTGAAAAAGCTGATCAACAAGAGCCCCGAAAAG CTGCTGATGTACCACCA

CGACCCCCAGACCTACCAGAAACTGAAGCTGATTATGGAACAGTACGGCGACGAGAA GAATCCCCTGTACAAGT

ACTACGAGGAAACCGGGAACTACCTGACCAAGTACTCCAAAAAGGACAACGGCCCCG TGATCAAGAAGATTAAG

TATTACGGCAACAAACTGAACGCCCATCTGGACATCACCGACGACTACCCCAACAGC AGAAACAAGGTCGTGAA

GCTGTCCCTGAAGCCCTACAGATTCGACGTGTACCTGGACAATGGCGTGTACAAGTT CGTGACCGTGAAGAATC

TGGATGTGATCAAAAAAGAAAACTACTACGAAGTGAATAGCAAGTGCTATGAGGAAG CTAAGAAGCTGAAGAAGA

TCAGCAACCAGGCCGAGTTTATCGCCTCCTTCTACAACAACGATCTGATCAAGATCA ACGGCGAGCTGTATAGA

GTGATCGGCGTGAACAACGACCTGCTGAACCGGATCGAAGTGAACATGATCGACATC ACCTACCGCGAGTACCT

GGAAAACATGAACGACAAGAGGCCCCCCAGGATCATTAAGACAATCGCCTCCAAGAC CCAGAGCATTAAGAAGT

ACAGCACAGACATTCTGGGCAACCTGTATGAAGTGAAATCTAAGAAGCACCCTCAGA TCATCAAAAAGGGCAAAA

GGCCGGCGGCCACGAAAAAGGCCGGCCAGGCAAAAAAGAAAAAGGGATCCGGACGGG CTGACGCATTGGACG

ATTTTGATCTGGATATGCTGGGAAGTGACGCCCTCGATGATTTTGACCTTGACATGC TTGGTTCGGATGCCCTTG

ATGACTTTGACCTCGACATGCTCGGCAGTGACGCCCTTGATGATTTCGACCTGGACA TGCTGATTAACTGTACAG

GCAGTGGAGAGGGCAGAGGAAGTCTGCTAACATGCGGTGACGTCGAGGAGAATCCTG GCCCAATGGCCAAGC

CTTTGTCTCAAGAAGAATCCACCCTCATTGAAAGAGCAACGGCTACAATCAACAGCA TCCCCATCTCTGAAGACT

ACAGCGTCGCCAGCGCAGCTCTCTCTAGCGACGGCCGCATCTTCACTGGTGTCAATG TATATCATTTTACTGGG GGACCTTGTGCAGAACTCGTGGTGCTGGGCACTGCTGCTGCTGCGGCAGCTGGCAACCTG ACTTGTATCGTCG

CGATCGGAAATGAGAACAGGGGCATCTTGAGCCCCTGCGGACGGTGCCGACAGGTGC TTCTCGATCTGCATCC

TGGGATCAAAGCCATAGTGAAGGACAGTGATGGACAGCCGACGGCAGTTGGGATTCG TGAATTGCTGCCCTCT

GGTTATGTGTGGGAGGGCTAAGAATTCCTAGAGCTCGCTGATCAGCCTCGACTGTGC CTTCTAGTTGCCAGCCA

TCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACT GTCCTTTCCTAATAAAAT

GAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTG GGGCAGGACAGCAAGG

GGGAGGATTGGGAAGAGAATAGCAGGCATGCTGGGGAGGTACCGAGGGCCTATTTCC CATGATTCCTTCATATT

TGCATATACGATACAAGGCTGTTAGAGAGATAATTGGAATTAATTTGACTGTAAACA CAAAGATATTAGTACAAAA

TACGTGACGTAGAAAGTAATAATTTCTTGGGTAGTTTGCAGTTTTAAAATTATGTTT TAAAATGGACTATCATATGC

TTACCGTAACTTGAAAGTATTTCGATTTCTTGGCTTTATATATCTTGTGGAAAGGAC GAAAcaccGAATTTAACTAG

CTGTATCCCgTTTTAGTACTCTGGAAACAGAATCTACTAAAACAAGGCAAAATGCCG TGTTTATCTCGTCAACTTG

TTGGCGAGATTTTTGCGGCCGCAGGAACCCCTAGTGATGGAGTTGGCCACTCCCTCT CTGCGCGCTCGCTCGC

TCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGGGCTTTGCCCGGGCGGCCT CAGTGAGCGAGCGA

GCGCGCAGCTGCCTGCAGGGGCGCCTGATGCGGTATTTTCTCCTTACGCATCTGTGC GGTATTTCACACCGCAT

ACGTCAAAGCAACCATAGTACGCGCCCTGTAGCGGCGCATTAAGCGCGGCGGGTGTG GTGGTTACGCGCAGC

GTGACCGCTACACTTGCCAGCGCCTTAGCGCCCGCTCCTTTCGCTTTCTTCCCTTCC TTTCTCGCCACGTTCGC

CGGCTTTCCCCGTCAAGCTCTAAATCGGGGGCTCCCTTTAGGGTTCCGATTTAGTGC TTTACGGCACCTCGACC

CCAAAAAACTTGATTTGGGTGATGGTTCACGTAGTGGGCCATCGCCCTGATAGACGG TTTTTCGCCCTTTGACGT

TGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAACTGGAACAACACTCAACT CTATCTCGGGCTATTCTTT

TGATTTATAAGGGATTTTGCCGATTTCGGTCTATTGGTTAAAAAATGAGCTGATTTA ACAAAAATTTAACGCGAATT

TTAACAAAATATTAACGTTTACAATTTTATGGTGCACTCTCAGTACAATCTGCTCTG ATGCCGCATAGTTAAGCCA

GCCCCGACACCCGCCAACACCCGCTGACGCGCCCTGACGGGCTTGTCTGCTCCCGGC ATCCGCTTACAGACAA

GCTGTGACCGTCTCCGGGAGCTGCATGTGTCAGAGGTTTTCACCGTCATCACCGAAA CGCGCGAGACGAAAGG

GCCTCGTGATACGCCTATTTTTATAGGTTAATGTCATGATAATAATGGTTTCTTAGA CGTCAGGTGGCACTTTTCG

GGGAAATGTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTA TCCGCTCATGAGACAATAA

CCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTC CGTGTCGCCCTTATTCCCT

TTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAA AAGATGCTGAAGATCAGTT

GGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAG TTTTCGCCCCGAAGAAC

GTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTA TTGACGCCGGGCAAGAGC

AACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCA CAGAAAAGCATCTTACGG

ATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTG CGGCCAACTTACTTCTGA

CAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATG TAACTCGCCTTGATCGT

TGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCT GTAGCAATGGCAACAA

CGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAA TAGACTGGATGGAGGCG

GATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCT GATAAATCTGGAGCCGG

TGAGCGTGGAAGCCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCG TATCGTAGTTATCTACA

CGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTG CCTCACTGATTAAGCAT

TGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCAT TTTTAATTTAAAAGGATCTAG

GTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTC CACTGAGCGTCAGACCCC

GTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGC TTGCAAACAAAAAAACCAC

CGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGG TAACTGGCTTCAGCAGA

GCGCAGATACCAAATACTGTTCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAG AACTCTGTAGCACCGCCT

ACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCG TGTCTTACCGGGTTGGA

CTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTG CACACAGCCCAGCTTG

GAGCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCC ACGCTTCCCGAAGGGA

GAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGG AGCTTCCAGGGGGA

AACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGA TTTTTGTGATGCTCGTCA

GGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCC TTTTGCTGGCCTTTTG

CTCACATGT pAAV-CMV-sadCas9-U6gRNA(Kcna 1-sa sgRNA7) used in in vitro qPCR experiments (SEQ ID NO: 62)

CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCGTCGGGCGACC TTTGGTCGCCCGGCC

TCAGTGAGCGAGCGAGCGCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCC TGCGGCCTCTAGACTC GAGGCGTTGACATTGATTATTGACTAGTTATTAATAGTAATCAATTACGGGGTCATTAGT TCATAGCCCATATATG

GAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGAC CCCCGCCCATTGACGT

CAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAAT GGGTGGAGTATTTACGGT

AAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTG ACGTCAATGACGGTAAAT

GGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGT ACATCTACGTATTAGTCA

TCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAATGGGCGTGGATAGCGGT TTGACTCACGGGGATTT

CCAAGTCTCCACCCCATTGACGTCAATGGGAGTTTGTTTTGGCACCAAAATCAACGG GACTTTCCAAAATGTCGT

AACAACTCCGCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTAT ATAAGCAGAGCTCTCT

GGCTAACTACCGGTGCCACCATGGCCCCAAAGAAGAAGCGGAAGGTCGGTATCCACG GAGTCCCAGCAGCCAA

GCGGAACTACATCCTGGGCCTGGCCATCGGCATCACCAGCGTGGGCTACGGCATCAT CGACTACGAGACACGG

GACGTGATCGATGCCGGCGTGCGGCTGTTCAAAGAGGCCAACGTGGAAAACAACGAG GGCAGGCGGAGCAAG

AGAGGCGCCAGAAGGCTGAAGCGGCGGAGGCGGCATAGAATCCAGAGAGTGAAGAAG CTGCTGTTCGACTAC

AACCTGCTGACCGACCACAGCGAGCTGAGCGGCATCAACCCCTACGAGGCCAGAGTG AAGGGCCTGAGCCAG

AAGCTGAGCGAGGAAGAGTTCTCTGCCGCCCTGCTGCACCTGGCCAAGAGAAGAGGC GTGCACAACGTGAACG

AGGTGGAAGAGGACACCGGCAACGAGCTGTCCACCAAAGAGCAGATCAGCCGGAACA GCAAGGCCCTGGAAG

AGAAATACGTGGCCGAACTGCAGCTGGAACGGCTGAAGAAAGACGGCGAAGTGCGGG GCAGCATCAACAGATT

CAAGACCAGCGACTACGTGAAAGAAGCCAAACAGCTGCTGAAGGTGCAGAAGGCCTA CCACCAGCTGGACCAG

AGCTTCATCGACACCTACATCGACCTGCTGGAAACCCGGCGGACCTACTATGAGGGA CCTGGCGAGGGCAGCC

CCTTCGGCTGGAAGGACATCAAAGAATGGTACGAGATGCTGATGGGCCACTGCACCT ACTTCCCCGAGGAACT

GCGGAGCGTGAAGTACGCCTACAACGCCGACCTGTACAACGCCCTGAACGACCTGAA CAATCTCGTGATCACC

AGGGACGAGAACGAGAAGCTGGAATATTACGAGAAGTTCCAGATCATCGAGAACGTG TTCAAGCAGAAGAAGAA

GCCCACCCTGAAGCAGATCGCCAAAGAAATCCTCGTGAACGAAGAGGATATTAAGGG CTACAGAGTGACCAGCA

CCGGCAAGCCCGAGTTCACCAACCTGAAGGTGTACCACGACATCAAGGACATTACCG CCCGGAAAGAGATTATT

GAGAACGCCGAGCTGCTGGATCAGATTGCCAAGATCCTGACCATCTACCAGAGCAGC GAGGACATCCAGGAAG

AACTGACCAATCTGAACTCCGAGCTGACCCAGGAAGAGATCGAGCAGATCTCTAATC TGAAGGGCTATACCGGC

ACCCACAACCTGAGCCTGAAGGCCATCAACCTGATCCTGGACGAGCTGTGGCACACC AACGACAACCAGATCG

CTATCTTCAACCGGCTGAAGCTGGTGCCCAAGAAGGTGGACCTGTCCCAGCAGAAAG AGATCCCCACCACCCT

GGTGGACGACTTCATCCTGAGCCCCGTCGTGAAGAGAAGCTTCATCCAGAGCATCAA AGTGATCAACGCCATCA

TCAAGAAGTACGGCCTGCCCAACGACATCATTATCGAGCTGGCCCGCGAGAAGAACT CCAAGGACGCCCAGAA

AATGATCAACGAGATGCAGAAGCGGAACCGGCAGACCAACGAGCGGATCGAGGAAAT CATCCGGACCACCGGC

AAAGAGAACGCCAAGTACCTGATCGAGAAGATCAAGCTGCACGACATGCAGGAAGGC AAGTGCCTGTACAGCC

TGGAAGCCATCCCTCTGGAAGATCTGCTGAACAACCCCTTCAACTATGAGGTGGACC ACATCATCCCCAGAAGC

GTGTCCTTCGACAACAGCTTCAACAACAAGGTGCTCGTGAAGCAGGAAGAAGCCAGC AAGAAGGGCAACCGGA

CCCCATTCCAGTACCTGAGCAGCAGCGACAGCAAGATCAGCTACGAAACCTTCAAGA AGCACATCCTGAATCTG

GCCAAGGGCAAGGGCAGAATCAGCAAGACCAAGAAAGAGTATCTGCTGGAAGAACGG GACATCAACAGGTTCT

CCGTGCAGAAAGACTTCATCAACCGGAACCTGGTGGATACCAGATACGCCACCAGAG GCCTGATGAACCTGCT

GCGGAGCTACTTCAGAGTGAACAACCTGGACGTGAAAGTGAAGTCCATCAATGGCGG CTTCACCAGCTTTCTGC

GGCGGAAGTGGAAGTTTAAGAAAGAGCGGAACAAGGGGTACAAGCACCACGCCGAGG ACGCCCTGATCATTGC

CAACGCCGATTTCATCTTCAAAGAGTGGAAGAAACTGGACAAGGCCAAAAAAGTGAT GGAAAACCAGATGTTCG

AGGAAAAGCAGGCCGAGAGCATGCCCGAGATCGAAACCGAGCAGGAGTACAAAGAGA TCTTCATCACCCCCCA

CCAGATCAAGCACATTAAGGACTTCAAGGACTACAAGTACAGCCACCGGGTGGACAA GAAGCCTAATAGAGAGC

TGATTAACGACACCCTGTACTCCACCCGGAAGGACGACAAGGGCAACACCCTGATCG TGAACAATCTGAACGGC

CTGTACGACAAGGACAATGACAAGCTGAAAAAGCTGATCAACAAGAGCCCCGAAAAG CTGCTGATGTACCACCA

CGACCCCCAGACCTACCAGAAACTGAAGCTGATTATGGAACAGTACGGCGACGAGAA GAATCCCCTGTACAAGT

ACTACGAGGAAACCGGGAACTACCTGACCAAGTACTCCAAAAAGGACAACGGCCCCG TGATCAAGAAGATTAAG

TATTACGGCAACAAACTGAACGCCCATCTGGACATCACCGACGACTACCCCAACAGC AGAAACAAGGTCGTGAA

GCTGTCCCTGAAGCCCTACAGATTCGACGTGTACCTGGACAATGGCGTGTACAAGTT CGTGACCGTGAAGAATC

TGGATGTGATCAAAAAAGAAAACTACTACGAAGTGAATAGCAAGTGCTATGAGGAAG CTAAGAAGCTGAAGAAGA

TCAGCAACCAGGCCGAGTTTATCGCCTCCTTCTACAACAACGATCTGATCAAGATCA ACGGCGAGCTGTATAGA

GTGATCGGCGTGAACAACGACCTGCTGAACCGGATCGAAGTGAACATGATCGACATC ACCTACCGCGAGTACCT

GGAAAACATGAACGACAAGAGGCCCCCCAGGATCATTAAGACAATCGCCTCCAAGAC CCAGAGCATTAAGAAGT

ACAGCACAGACATTCTGGGCAACCTGTATGAAGTGAAATCTAAGAAGCACCCTCAGA TCATCAAAAAGGGCAAAA

GGCCGGCGGCCACGAAAAAGGCCGGCCAGGCAAAAAAGAAAAAGGGATCCGGACGGG CTGACGCATTGGACG ATTTTGATCTGGATATGCTGGGAAGTGACGCCCTCGATGATTTTGACCTTGACATGCTTG GTTCGGATGCCCTTG

ATGACTTTGACCTCGACATGCTCGGCAGTGACGCCCTTGATGATTTCGACCTGGACA TGCTGATTAACTGTACAG

GCAGTGGAGAGGGCAGAGGAAGTCTGCTAACATGCGGTGACGTCGAGGAGAATCCTG GCCCAATGGCCAAGC

CTTTGTCTCAAGAAGAATCCACCCTCATTGAAAGAGCAACGGCTACAATCAACAGCA TCCCCATCTCTGAAGACT

ACAGCGTCGCCAGCGCAGCTCTCTCTAGCGACGGCCGCATCTTCACTGGTGTCAATG TATATCATTTTACTGGG

GGACCTTGTGCAGAACTCGTGGTGCTGGGCACTGCTGCTGCTGCGGCAGCTGGCAAC CTGACTTGTATCGTCG

CGATCGGAAATGAGAACAGGGGCATCTTGAGCCCCTGCGGACGGTGCCGACAGGTGC TTCTCGATCTGCATCC

TGGGATCAAAGCCATAGTGAAGGACAGTGATGGACAGCCGACGGCAGTTGGGATTCG TGAATTGCTGCCCTCT

GGTTATGTGTGGGAGGGCTAAGAATTCCTAGAGCTCGCTGATCAGCCTCGACTGTGC CTTCTAGTTGCCAGCCA

TCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACT GTCCTTTCCTAATAAAAT

GAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTG GGGCAGGACAGCAAGG

GGGAGGATTGGGAAGAGAATAGCAGGCATGCTGGGGAGGTACCGAGGGCCTATTTCC CATGATTCCTTCATATT

TGCATATACGATACAAGGCTGTTAGAGAGATAATTGGAATTAATTTGACTGTAAACA CAAAGATATTAGTACAAAA

TACGTGACGTAGAAAGTAATAATTTCTTGGGTAGTTTGCAGTTTTAAAATTATGTTT TAAAATGGACTATCATATGC

TTACCGTAACTTGAAAGTATTTCGATTTCTTGGCTTTATATATCTTGTGGAAAGGAC GAAAcaccTACTAGCCACAA

TAGAGCCAGgTTTTAGTACTCTGGAAACAGAATCTACTAAAACAAGGCAAAATGCCG TGTTTATCTCGTCAACTTG

TTGGCGAGATTTTTGCGGCCGCAGGAACCCCTAGTGATGGAGTTGGCCACTCCCTCT CTGCGCGCTCGCTCGC

TCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGGGCTTTGCCCGGGCGGCCT CAGTGAGCGAGCGA

GCGCGCAGCTGCCTGCAGGGGCGCCTGATGCGGTATTTTCTCCTTACGCATCTGTGC GGTATTTCACACCGCAT

ACGTCAAAGCAACCATAGTACGCGCCCTGTAGCGGCGCATTAAGCGCGGCGGGTGTG GTGGTTACGCGCAGC

GTGACCGCTACACTTGCCAGCGCCTTAGCGCCCGCTCCTTTCGCTTTCTTCCCTTCC TTTCTCGCCACGTTCGC

CGGCTTTCCCCGTCAAGCTCTAAATCGGGGGCTCCCTTTAGGGTTCCGATTTAGTGC TTTACGGCACCTCGACC

CCAAAAAACTTGATTTGGGTGATGGTTCACGTAGTGGGCCATCGCCCTGATAGACGG TTTTTCGCCCTTTGACGT

TGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAACTGGAACAACACTCAACT CTATCTCGGGCTATTCTTT

TGATTTATAAGGGATTTTGCCGATTTCGGTCTATTGGTTAAAAAATGAGCTGATTTA ACAAAAATTTAACGCGAATT

TTAACAAAATATTAACGTTTACAATTTTATGGTGCACTCTCAGTACAATCTGCTCTG ATGCCGCATAGTTAAGCCA

GCCCCGACACCCGCCAACACCCGCTGACGCGCCCTGACGGGCTTGTCTGCTCCCGGC ATCCGCTTACAGACAA

GCTGTGACCGTCTCCGGGAGCTGCATGTGTCAGAGGTTTTCACCGTCATCACCGAAA CGCGCGAGACGAAAGG

GCCTCGTGATACGCCTATTTTTATAGGTTAATGTCATGATAATAATGGTTTCTTAGA CGTCAGGTGGCACTTTTCG

GGGAAATGTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTA TCCGCTCATGAGACAATAA

CCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTC CGTGTCGCCCTTATTCCCT

TTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAA AAGATGCTGAAGATCAGTT

GGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAG TTTTCGCCCCGAAGAAC

GTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTA TTGACGCCGGGCAAGAGC

AACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCA CAGAAAAGCATCTTACGG

ATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTG CGGCCAACTTACTTCTGA

CAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATG TAACTCGCCTTGATCGT

TGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCT GTAGCAATGGCAACAA

CGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAA TAGACTGGATGGAGGCG

GATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCT GATAAATCTGGAGCCGG

TGAGCGTGGAAGCCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCG TATCGTAGTTATCTACA

CGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTG CCTCACTGATTAAGCAT

TGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCAT TTTTAATTTAAAAGGATCTAG

GTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTC CACTGAGCGTCAGACCCC

GTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGC TTGCAAACAAAAAAACCAC

CGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGG TAACTGGCTTCAGCAGA

GCGCAGATACCAAATACTGTTCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAG AACTCTGTAGCACCGCCT

ACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCG TGTCTTACCGGGTTGGA

CTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTG CACACAGCCCAGCTTG

GAGCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCC ACGCTTCCCGAAGGGA

GAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGG AGCTTCCAGGGGGA

AACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGA TTTTTGTGATGCTCGTCA GGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCCTTT TGCTGGCCTTTTG

CTCACATGT

1.3 KCNA2

Nucleotide sequence of sasgRNA for mouse KCNA2; sgRNA1 (SEQ ID NO: 63)

CCGCCGCCGCCAAGCTGGCCA

Nucleotide sequence of sasgRNA for mouse KCNA2; sgRNA2 (SEQ ID NO: 64)

GCCCCAGCCGGCCCCTTTAAT

Nucleotide sequence of sasgRNA for mouse KCNA2; sgRNA3 (SEQ ID NO: 65)

CCCGCAGCGAACTCGAATTAA pAAV-CMV-sadCas9-U6gRNA(Kcna2-sa sgRNA1) used in in vitro qPCR experiments (SEQ ID NO: 66)

CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCGTCGGGCGACC TTTGGTCGCCCGGCC

TCAGTGAGCGAGCGAGCGCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCC TGCGGCCTCTAGACTC

GAGGCGTTGACATTGATTATTGACTAGTTATTAATAGTAATCAATTACGGGGTCATT AGTTCATAGCCCATATATG

GAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGAC CCCCGCCCATTGACGT

CAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAAT GGGTGGAGTATTTACGGT

AAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTG ACGTCAATGACGGTAAAT

GGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGT ACATCTACGTATTAGTCA

TCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAATGGGCGTGGATAGCGGT TTGACTCACGGGGATTT

CCAAGTCTCCACCCCATTGACGTCAATGGGAGTTTGTTTTGGCACCAAAATCAACGG GACTTTCCAAAATGTCGT

AACAACTCCGCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTAT ATAAGCAGAGCTCTCT

GGCTAACTACCGGTGCCACCATGGCCCCAAAGAAGAAGCGGAAGGTCGGTATCCACG GAGTCCCAGCAGCCAA

GCGGAACTACATCCTGGGCCTGGCCATCGGCATCACCAGCGTGGGCTACGGCATCAT CGACTACGAGACACGG

GACGTGATCGATGCCGGCGTGCGGCTGTTCAAAGAGGCCAACGTGGAAAACAACGAG GGCAGGCGGAGCAAG

AGAGGCGCCAGAAGGCTGAAGCGGCGGAGGCGGCATAGAATCCAGAGAGTGAAGAAG CTGCTGTTCGACTAC

AACCTGCTGACCGACCACAGCGAGCTGAGCGGCATCAACCCCTACGAGGCCAGAGTG AAGGGCCTGAGCCAG

AAGCTGAGCGAGGAAGAGTTCTCTGCCGCCCTGCTGCACCTGGCCAAGAGAAGAGGC GTGCACAACGTGAACG

AGGTGGAAGAGGACACCGGCAACGAGCTGTCCACCAAAGAGCAGATCAGCCGGAACA GCAAGGCCCTGGAAG

AGAAATACGTGGCCGAACTGCAGCTGGAACGGCTGAAGAAAGACGGCGAAGTGCGGG GCAGCATCAACAGATT

CAAGACCAGCGACTACGTGAAAGAAGCCAAACAGCTGCTGAAGGTGCAGAAGGCCTA CCACCAGCTGGACCAG

AGCTTCATCGACACCTACATCGACCTGCTGGAAACCCGGCGGACCTACTATGAGGGA CCTGGCGAGGGCAGCC

CCTTCGGCTGGAAGGACATCAAAGAATGGTACGAGATGCTGATGGGCCACTGCACCT ACTTCCCCGAGGAACT

GCGGAGCGTGAAGTACGCCTACAACGCCGACCTGTACAACGCCCTGAACGACCTGAA CAATCTCGTGATCACC

AGGGACGAGAACGAGAAGCTGGAATATTACGAGAAGTTCCAGATCATCGAGAACGTG TTCAAGCAGAAGAAGAA

GCCCACCCTGAAGCAGATCGCCAAAGAAATCCTCGTGAACGAAGAGGATATTAAGGG CTACAGAGTGACCAGCA

CCGGCAAGCCCGAGTTCACCAACCTGAAGGTGTACCACGACATCAAGGACATTACCG CCCGGAAAGAGATTATT

GAGAACGCCGAGCTGCTGGATCAGATTGCCAAGATCCTGACCATCTACCAGAGCAGC GAGGACATCCAGGAAG

AACTGACCAATCTGAACTCCGAGCTGACCCAGGAAGAGATCGAGCAGATCTCTAATC TGAAGGGCTATACCGGC

ACCCACAACCTGAGCCTGAAGGCCATCAACCTGATCCTGGACGAGCTGTGGCACACC AACGACAACCAGATCG

CTATCTTCAACCGGCTGAAGCTGGTGCCCAAGAAGGTGGACCTGTCCCAGCAGAAAG AGATCCCCACCACCCT

GGTGGACGACTTCATCCTGAGCCCCGTCGTGAAGAGAAGCTTCATCCAGAGCATCAA AGTGATCAACGCCATCA

TCAAGAAGTACGGCCTGCCCAACGACATCATTATCGAGCTGGCCCGCGAGAAGAACT CCAAGGACGCCCAGAA

AATGATCAACGAGATGCAGAAGCGGAACCGGCAGACCAACGAGCGGATCGAGGAAAT CATCCGGACCACCGGC

AAAGAGAACGCCAAGTACCTGATCGAGAAGATCAAGCTGCACGACATGCAGGAAGGC AAGTGCCTGTACAGCC

TGGAAGCCATCCCTCTGGAAGATCTGCTGAACAACCCCTTCAACTATGAGGTGGACC ACATCATCCCCAGAAGC

GTGTCCTTCGACAACAGCTTCAACAACAAGGTGCTCGTGAAGCAGGAAGAAGCCAGC AAGAAGGGCAACCGGA

CCCCATTCCAGTACCTGAGCAGCAGCGACAGCAAGATCAGCTACGAAACCTTCAAGA AGCACATCCTGAATCTG

GCCAAGGGCAAGGGCAGAATCAGCAAGACCAAGAAAGAGTATCTGCTGGAAGAACGG GACATCAACAGGTTCT CCGTGCAGAAAGACTTCATCAACCGGAACCTGGTGGATACCAGATACGCCACCAGAGGCC TGATGAACCTGCT

GCGGAGCTACTTCAGAGTGAACAACCTGGACGTGAAAGTGAAGTCCATCAATGGCGG CTTCACCAGCTTTCTGC

GGCGGAAGTGGAAGTTTAAGAAAGAGCGGAACAAGGGGTACAAGCACCACGCCGAGG ACGCCCTGATCATTGC

CAACGCCGATTTCATCTTCAAAGAGTGGAAGAAACTGGACAAGGCCAAAAAAGTGAT GGAAAACCAGATGTTCG

AGGAAAAGCAGGCCGAGAGCATGCCCGAGATCGAAACCGAGCAGGAGTACAAAGAGA TCTTCATCACCCCCCA

CCAGATCAAGCACATTAAGGACTTCAAGGACTACAAGTACAGCCACCGGGTGGACAA GAAGCCTAATAGAGAGC

TGATTAACGACACCCTGTACTCCACCCGGAAGGACGACAAGGGCAACACCCTGATCG TGAACAATCTGAACGGC

CTGTACGACAAGGACAATGACAAGCTGAAAAAGCTGATCAACAAGAGCCCCGAAAAG CTGCTGATGTACCACCA

CGACCCCCAGACCTACCAGAAACTGAAGCTGATTATGGAACAGTACGGCGACGAGAA GAATCCCCTGTACAAGT

ACTACGAGGAAACCGGGAACTACCTGACCAAGTACTCCAAAAAGGACAACGGCCCCG TGATCAAGAAGATTAAG

TATTACGGCAACAAACTGAACGCCCATCTGGACATCACCGACGACTACCCCAACAGC AGAAACAAGGTCGTGAA

GCTGTCCCTGAAGCCCTACAGATTCGACGTGTACCTGGACAATGGCGTGTACAAGTT CGTGACCGTGAAGAATC

TGGATGTGATCAAAAAAGAAAACTACTACGAAGTGAATAGCAAGTGCTATGAGGAAG CTAAGAAGCTGAAGAAGA

TCAGCAACCAGGCCGAGTTTATCGCCTCCTTCTACAACAACGATCTGATCAAGATCA ACGGCGAGCTGTATAGA

GTGATCGGCGTGAACAACGACCTGCTGAACCGGATCGAAGTGAACATGATCGACATC ACCTACCGCGAGTACCT

GGAAAACATGAACGACAAGAGGCCCCCCAGGATCATTAAGACAATCGCCTCCAAGAC CCAGAGCATTAAGAAGT

ACAGCACAGACATTCTGGGCAACCTGTATGAAGTGAAATCTAAGAAGCACCCTCAGA TCATCAAAAAGGGCAAAA

GGCCGGCGGCCACGAAAAAGGCCGGCCAGGCAAAAAAGAAAAAGGGATCCGGACGGG CTGACGCATTGGACG

ATTTTGATCTGGATATGCTGGGAAGTGACGCCCTCGATGATTTTGACCTTGACATGC TTGGTTCGGATGCCCTTG

ATGACTTTGACCTCGACATGCTCGGCAGTGACGCCCTTGATGATTTCGACCTGGACA TGCTGATTAACTGTACAG

GCAGTGGAGAGGGCAGAGGAAGTCTGCTAACATGCGGTGACGTCGAGGAGAATCCTG GCCCAATGGCCAAGC

CTTTGTCTCAAGAAGAATCCACCCTCATTGAAAGAGCAACGGCTACAATCAACAGCA TCCCCATCTCTGAAGACT

ACAGCGTCGCCAGCGCAGCTCTCTCTAGCGACGGCCGCATCTTCACTGGTGTCAATG TATATCATTTTACTGGG

GGACCTTGTGCAGAACTCGTGGTGCTGGGCACTGCTGCTGCTGCGGCAGCTGGCAAC CTGACTTGTATCGTCG

CGATCGGAAATGAGAACAGGGGCATCTTGAGCCCCTGCGGACGGTGCCGACAGGTGC TTCTCGATCTGCATCC

TGGGATCAAAGCCATAGTGAAGGACAGTGATGGACAGCCGACGGCAGTTGGGATTCG TGAATTGCTGCCCTCT

GGTTATGTGTGGGAGGGCTAAGAATTCCTAGAGCTCGCTGATCAGCCTCGACTGTGC CTTCTAGTTGCCAGCCA

TCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACT GTCCTTTCCTAATAAAAT

GAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTG GGGCAGGACAGCAAGG

GGGAGGATTGGGAAGAGAATAGCAGGCATGCTGGGGAGGTACCGAGGGCCTATTTCC CATGATTCCTTCATATT

TGCATATACGATACAAGGCTGTTAGAGAGATAATTGGAATTAATTTGACTGTAAACA CAAAGATATTAGTACAAAA

TACGTGACGTAGAAAGTAATAATTTCTTGGGTAGTTTGCAGTTTTAAAATTATGTTT TAAAATGGACTATCATATGC

TTACCGTAACTTGAAAGTATTTCGATTTCTTGGCTTTATATATCTTGTGGAAAGGAC GAAAcaccGCCGCCGCCGC

CAAGCTGGCCAgTTTTAGTACTCTGGAAACAGAATCTACTAAAACAAGGCAAAATGC CGTGTTTATCTCGTCAACT

TGTTGGCGAGATTTTTGCGGCCGCAGGAACCCCTAGTGATGGAGTTGGCCACTCCCT CTCTGCGCGCTCGCTC

GCTCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGGGCTTTGCCCGGGCGGC CTCAGTGAGCGAGC

GAGCGCGCAGCTGCCTGCAGGGGCGCCTGATGCGGTATTTTCTCCTTACGCATCTGT GCGGTATTTCACACCG

CATACGTCAAAGCAACCATAGTACGCGCCCTGTAGCGGCGCATTAAGCGCGGCGGGT GTGGTGGTTACGCGCA

GCGTGACCGCTACACTTGCCAGCGCCTTAGCGCCCGCTCCTTTCGCTTTCTTCCCTT CCTTTCTCGCCACGTTC

GCCGGCTTTCCCCGTCAAGCTCTAAATCGGGGGCTCCCTTTAGGGTTCCGATTTAGT GCTTTACGGCACCTCGA

CCCCAAAAAACTTGATTTGGGTGATGGTTCACGTAGTGGGCCATCGCCCTGATAGAC GGTTTTTCGCCCTTTGAC

GTTGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAACTGGAACAACACTCAA CTCTATCTCGGGCTATTCT

TTTGATTTATAAGGGATTTTGCCGATTTCGGTCTATTGGTTAAAAAATGAGCTGATT TAACAAAAATTTAACGCGAA

TTTTAACAAAATATTAACGTTTACAATTTTATGGTGCACTCTCAGTACAATCTGCTC TGATGCCGCATAGTTAAGCC

AGCCCCGACACCCGCCAACACCCGCTGACGCGCCCTGACGGGCTTGTCTGCTCCCGG CATCCGCTTACAGACA

AGCTGTGACCGTCTCCGGGAGCTGCATGTGTCAGAGGTTTTCACCGTCATCACCGAA ACGCGCGAGACGAAAG

GGCCTCGTGATACGCCTATTTTTATAGGTTAATGTCATGATAATAATGGTTTCTTAG ACGTCAGGTGGCACTTTTC

GGGGAAATGTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGT ATCCGCTCATGAGACAATA

ACCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTT CCGTGTCGCCCTTATTCCC

TTTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTA AAAGATGCTGAAGATCAGT

TGGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGA GTTTTCGCCCCGAAGAA

CGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGT ATTGACGCCGGGCAAGAG

CAACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTC ACAGAAAAGCATCTTACG GATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTGCG GCCAACTTACTTCTG

ACAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCAT GTAACTCGCCTTGATCG

TTGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCC TGTAGCAATGGCAACA

ACGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTA ATAGACTGGATGGAGGCG

GATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCT GATAAATCTGGAGCCGG

TGAGCGTGGAAGCCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCG TATCGTAGTTATCTACA

CGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTG CCTCACTGATTAAGCAT

TGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCAT TTTTAATTTAAAAGGATCTAG

GTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTC CACTGAGCGTCAGACCCC

GTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGC TTGCAAACAAAAAAACCAC

CGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGG TAACTGGCTTCAGCAGA

GCGCAGATACCAAATACTGTTCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAG AACTCTGTAGCACCGCCT

ACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCG TGTCTTACCGGGTTGGA

CTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTG CACACAGCCCAGCTTG

GAGCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCC ACGCTTCCCGAAGGGA

GAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGG AGCTTCCAGGGGGA

AACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGA TTTTTGTGATGCTCGTCA

GGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCC TTTTGCTGGCCTTTTG CTCACATGT pAAV-CMV-sadCas9-U6gRNA(Kcna2-sa sgRNA2) used in in vitro qPCR experiments (SEQ ID NO: 67)

CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCGTCGGGCGACC TTTGGTCGCCCGGCC

TCAGTGAGCGAGCGAGCGCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCC TGCGGCCTCTAGACTC

GAGGCGTTGACATTGATTATTGACTAGTTATTAATAGTAATCAATTACGGGGTCATT AGTTCATAGCCCATATATG

GAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGAC CCCCGCCCATTGACGT

CAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAAT GGGTGGAGTATTTACGGT

AAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTG ACGTCAATGACGGTAAAT

GGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGT ACATCTACGTATTAGTCA

TCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAATGGGCGTGGATAGCGGT TTGACTCACGGGGATTT

CCAAGTCTCCACCCCATTGACGTCAATGGGAGTTTGTTTTGGCACCAAAATCAACGG GACTTTCCAAAATGTCGT

AACAACTCCGCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTAT ATAAGCAGAGCTCTCT

GGCTAACTACCGGTGCCACCATGGCCCCAAAGAAGAAGCGGAAGGTCGGTATCCACG GAGTCCCAGCAGCCAA

GCGGAACTACATCCTGGGCCTGGCCATCGGCATCACCAGCGTGGGCTACGGCATCAT CGACTACGAGACACGG

GACGTGATCGATGCCGGCGTGCGGCTGTTCAAAGAGGCCAACGTGGAAAACAACGAG GGCAGGCGGAGCAAG

AGAGGCGCCAGAAGGCTGAAGCGGCGGAGGCGGCATAGAATCCAGAGAGTGAAGAAG CTGCTGTTCGACTAC

AACCTGCTGACCGACCACAGCGAGCTGAGCGGCATCAACCCCTACGAGGCCAGAGTG AAGGGCCTGAGCCAG

AAGCTGAGCGAGGAAGAGTTCTCTGCCGCCCTGCTGCACCTGGCCAAGAGAAGAGGC GTGCACAACGTGAACG

AGGTGGAAGAGGACACCGGCAACGAGCTGTCCACCAAAGAGCAGATCAGCCGGAACA GCAAGGCCCTGGAAG

AGAAATACGTGGCCGAACTGCAGCTGGAACGGCTGAAGAAAGACGGCGAAGTGCGGG GCAGCATCAACAGATT

CAAGACCAGCGACTACGTGAAAGAAGCCAAACAGCTGCTGAAGGTGCAGAAGGCCTA CCACCAGCTGGACCAG

AGCTTCATCGACACCTACATCGACCTGCTGGAAACCCGGCGGACCTACTATGAGGGA CCTGGCGAGGGCAGCC

CCTTCGGCTGGAAGGACATCAAAGAATGGTACGAGATGCTGATGGGCCACTGCACCT ACTTCCCCGAGGAACT

GCGGAGCGTGAAGTACGCCTACAACGCCGACCTGTACAACGCCCTGAACGACCTGAA CAATCTCGTGATCACC

AGGGACGAGAACGAGAAGCTGGAATATTACGAGAAGTTCCAGATCATCGAGAACGTG TTCAAGCAGAAGAAGAA

GCCCACCCTGAAGCAGATCGCCAAAGAAATCCTCGTGAACGAAGAGGATATTAAGGG CTACAGAGTGACCAGCA

CCGGCAAGCCCGAGTTCACCAACCTGAAGGTGTACCACGACATCAAGGACATTACCG CCCGGAAAGAGATTATT

GAGAACGCCGAGCTGCTGGATCAGATTGCCAAGATCCTGACCATCTACCAGAGCAGC GAGGACATCCAGGAAG

AACTGACCAATCTGAACTCCGAGCTGACCCAGGAAGAGATCGAGCAGATCTCTAATC TGAAGGGCTATACCGGC

ACCCACAACCTGAGCCTGAAGGCCATCAACCTGATCCTGGACGAGCTGTGGCACACC AACGACAACCAGATCG

CTATCTTCAACCGGCTGAAGCTGGTGCCCAAGAAGGTGGACCTGTCCCAGCAGAAAG AGATCCCCACCACCCT

GGTGGACGACTTCATCCTGAGCCCCGTCGTGAAGAGAAGCTTCATCCAGAGCATCAA AGTGATCAACGCCATCA

TCAAGAAGTACGGCCTGCCCAACGACATCATTATCGAGCTGGCCCGCGAGAAGAACT CCAAGGACGCCCAGAA

AATGATCAACGAGATGCAGAAGCGGAACCGGCAGACCAACGAGCGGATCGAGGAAAT CATCCGGACCACCGGC AAAGAGAACGCCAAGTACCTGATCGAGAAGATCAAGCTGCACGACATGCAGGAAGGCAAG TGCCTGTACAGCC

TGGAAGCCATCCCTCTGGAAGATCTGCTGAACAACCCCTTCAACTATGAGGTGGACC ACATCATCCCCAGAAGC

GTGTCCTTCGACAACAGCTTCAACAACAAGGTGCTCGTGAAGCAGGAAGAAGCCAGC AAGAAGGGCAACCGGA

CCCCATTCCAGTACCTGAGCAGCAGCGACAGCAAGATCAGCTACGAAACCTTCAAGA AGCACATCCTGAATCTG

GCCAAGGGCAAGGGCAGAATCAGCAAGACCAAGAAAGAGTATCTGCTGGAAGAACGG GACATCAACAGGTTCT

CCGTGCAGAAAGACTTCATCAACCGGAACCTGGTGGATACCAGATACGCCACCAGAG GCCTGATGAACCTGCT

GCGGAGCTACTTCAGAGTGAACAACCTGGACGTGAAAGTGAAGTCCATCAATGGCGG CTTCACCAGCTTTCTGC

GGCGGAAGTGGAAGTTTAAGAAAGAGCGGAACAAGGGGTACAAGCACCACGCCGAGG ACGCCCTGATCATTGC

CAACGCCGATTTCATCTTCAAAGAGTGGAAGAAACTGGACAAGGCCAAAAAAGTGAT GGAAAACCAGATGTTCG

AGGAAAAGCAGGCCGAGAGCATGCCCGAGATCGAAACCGAGCAGGAGTACAAAGAGA TCTTCATCACCCCCCA

CCAGATCAAGCACATTAAGGACTTCAAGGACTACAAGTACAGCCACCGGGTGGACAA GAAGCCTAATAGAGAGC

TGATTAACGACACCCTGTACTCCACCCGGAAGGACGACAAGGGCAACACCCTGATCG TGAACAATCTGAACGGC

CTGTACGACAAGGACAATGACAAGCTGAAAAAGCTGATCAACAAGAGCCCCGAAAAG CTGCTGATGTACCACCA

CGACCCCCAGACCTACCAGAAACTGAAGCTGATTATGGAACAGTACGGCGACGAGAA GAATCCCCTGTACAAGT

ACTACGAGGAAACCGGGAACTACCTGACCAAGTACTCCAAAAAGGACAACGGCCCCG TGATCAAGAAGATTAAG

TATTACGGCAACAAACTGAACGCCCATCTGGACATCACCGACGACTACCCCAACAGC AGAAACAAGGTCGTGAA

GCTGTCCCTGAAGCCCTACAGATTCGACGTGTACCTGGACAATGGCGTGTACAAGTT CGTGACCGTGAAGAATC

TGGATGTGATCAAAAAAGAAAACTACTACGAAGTGAATAGCAAGTGCTATGAGGAAG CTAAGAAGCTGAAGAAGA

TCAGCAACCAGGCCGAGTTTATCGCCTCCTTCTACAACAACGATCTGATCAAGATCA ACGGCGAGCTGTATAGA

GTGATCGGCGTGAACAACGACCTGCTGAACCGGATCGAAGTGAACATGATCGACATC ACCTACCGCGAGTACCT

GGAAAACATGAACGACAAGAGGCCCCCCAGGATCATTAAGACAATCGCCTCCAAGAC CCAGAGCATTAAGAAGT

ACAGCACAGACATTCTGGGCAACCTGTATGAAGTGAAATCTAAGAAGCACCCTCAGA TCATCAAAAAGGGCAAAA

GGCCGGCGGCCACGAAAAAGGCCGGCCAGGCAAAAAAGAAAAAGGGATCCGGACGGG CTGACGCATTGGACG

ATTTTGATCTGGATATGCTGGGAAGTGACGCCCTCGATGATTTTGACCTTGACATGC TTGGTTCGGATGCCCTTG

ATGACTTTGACCTCGACATGCTCGGCAGTGACGCCCTTGATGATTTCGACCTGGACA TGCTGATTAACTGTACAG

GCAGTGGAGAGGGCAGAGGAAGTCTGCTAACATGCGGTGACGTCGAGGAGAATCCTG GCCCAATGGCCAAGC

CTTTGTCTCAAGAAGAATCCACCCTCATTGAAAGAGCAACGGCTACAATCAACAGCA TCCCCATCTCTGAAGACT

ACAGCGTCGCCAGCGCAGCTCTCTCTAGCGACGGCCGCATCTTCACTGGTGTCAATG TATATCATTTTACTGGG

GGACCTTGTGCAGAACTCGTGGTGCTGGGCACTGCTGCTGCTGCGGCAGCTGGCAAC CTGACTTGTATCGTCG

CGATCGGAAATGAGAACAGGGGCATCTTGAGCCCCTGCGGACGGTGCCGACAGGTGC TTCTCGATCTGCATCC

TGGGATCAAAGCCATAGTGAAGGACAGTGATGGACAGCCGACGGCAGTTGGGATTCG TGAATTGCTGCCCTCT

GGTTATGTGTGGGAGGGCTAAGAATTCCTAGAGCTCGCTGATCAGCCTCGACTGTGC CTTCTAGTTGCCAGCCA

TCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACT GTCCTTTCCTAATAAAAT

GAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTG GGGCAGGACAGCAAGG

GGGAGGATTGGGAAGAGAATAGCAGGCATGCTGGGGAGGTACCGAGGGCCTATTTCC CATGATTCCTTCATATT

TGCATATACGATACAAGGCTGTTAGAGAGATAATTGGAATTAATTTGACTGTAAACA CAAAGATATTAGTACAAAA

TACGTGACGTAGAAAGTAATAATTTCTTGGGTAGTTTGCAGTTTTAAAATTATGTTT TAAAATGGACTATCATATGC

TTACCGTAACTTGAAAGTATTTCGATTTCTTGGCTTTATATATCTTGTGGAAAGGAC GAAAcaccGCCCCAGCCGG

CCCCTTTAATgTTTTAGTACTCTGGAAACAGAATCTACTAAAACAAGGCAAAATGCC GTGTTTATCTCGTCAACTT

GTTGGCGAGATTTTTGCGGCCGCAGGAACCCCTAGTGATGGAGTTGGCCACTCCCTC TCTGCGCGCTCGCTCG

CTCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGGGCTTTGCCCGGGCGGCC TCAGTGAGCGAGCG

AGCGCGCAGCTGCCTGCAGGGGCGCCTGATGCGGTATTTTCTCCTTACGCATCTGTG CGGTATTTCACACCGCA

TACGTCAAAGCAACCATAGTACGCGCCCTGTAGCGGCGCATTAAGCGCGGCGGGTGT GGTGGTTACGCGCAGC

GTGACCGCTACACTTGCCAGCGCCTTAGCGCCCGCTCCTTTCGCTTTCTTCCCTTCC TTTCTCGCCACGTTCGC

CGGCTTTCCCCGTCAAGCTCTAAATCGGGGGCTCCCTTTAGGGTTCCGATTTAGTGC TTTACGGCACCTCGACC

CCAAAAAACTTGATTTGGGTGATGGTTCACGTAGTGGGCCATCGCCCTGATAGACGG TTTTTCGCCCTTTGACGT

TGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAACTGGAACAACACTCAACT CTATCTCGGGCTATTCTTT

TGATTTATAAGGGATTTTGCCGATTTCGGTCTATTGGTTAAAAAATGAGCTGATTTA ACAAAAATTTAACGCGAATT

TTAACAAAATATTAACGTTTACAATTTTATGGTGCACTCTCAGTACAATCTGCTCTG ATGCCGCATAGTTAAGCCA

GCCCCGACACCCGCCAACACCCGCTGACGCGCCCTGACGGGCTTGTCTGCTCCCGGC ATCCGCTTACAGACAA

GCTGTGACCGTCTCCGGGAGCTGCATGTGTCAGAGGTTTTCACCGTCATCACCGAAA CGCGCGAGACGAAAGG

GCCTCGTGATACGCCTATTTTTATAGGTTAATGTCATGATAATAATGGTTTCTTAGA CGTCAGGTGGCACTTTTCG

GGGAAATGTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTA TCCGCTCATGAGACAATAA CCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTCCGT GTCGCCCTTATTCCCT

TTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAA AAGATGCTGAAGATCAGTT

GGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAG TTTTCGCCCCGAAGAAC

GTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTA TTGACGCCGGGCAAGAGC

AACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCA CAGAAAAGCATCTTACGG

ATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTG CGGCCAACTTACTTCTGA

CAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATG TAACTCGCCTTGATCGT

TGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCT GTAGCAATGGCAACAA

CGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAA TAGACTGGATGGAGGCG

GATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCT GATAAATCTGGAGCCGG

TGAGCGTGGAAGCCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCG TATCGTAGTTATCTACA

CGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTG CCTCACTGATTAAGCAT

TGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCAT TTTTAATTTAAAAGGATCTAG

GTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTC CACTGAGCGTCAGACCCC

GTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGC TTGCAAACAAAAAAACCAC

CGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGG TAACTGGCTTCAGCAGA

GCGCAGATACCAAATACTGTTCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAG AACTCTGTAGCACCGCCT

ACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCG TGTCTTACCGGGTTGGA

CTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTG CACACAGCCCAGCTTG

GAGCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCC ACGCTTCCCGAAGGGA

GAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGG AGCTTCCAGGGGGA

AACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGA TTTTTGTGATGCTCGTCA

GGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCC TTTTGCTGGCCTTTTG CTCACATGT pAAV-CMV-sadCas9-U6gRNA(Kcna2-sa sgRNA3) used in in vitro qPCR experiments (SEQ ID NO: 68)

CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCGTCGGGCGACC TTTGGTCGCCCGGCC

TCAGTGAGCGAGCGAGCGCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCC TGCGGCCTCTAGACTC

GAGGCGTTGACATTGATTATTGACTAGTTATTAATAGTAATCAATTACGGGGTCATT AGTTCATAGCCCATATATG

GAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGAC CCCCGCCCATTGACGT

CAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAAT GGGTGGAGTATTTACGGT

AAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTG ACGTCAATGACGGTAAAT

GGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGT ACATCTACGTATTAGTCA

TCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAATGGGCGTGGATAGCGGT TTGACTCACGGGGATTT

CCAAGTCTCCACCCCATTGACGTCAATGGGAGTTTGTTTTGGCACCAAAATCAACGG GACTTTCCAAAATGTCGT

AACAACTCCGCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTAT ATAAGCAGAGCTCTCT

GGCTAACTACCGGTGCCACCATGGCCCCAAAGAAGAAGCGGAAGGTCGGTATCCACG GAGTCCCAGCAGCCAA

GCGGAACTACATCCTGGGCCTGGCCATCGGCATCACCAGCGTGGGCTACGGCATCAT CGACTACGAGACACGG

GACGTGATCGATGCCGGCGTGCGGCTGTTCAAAGAGGCCAACGTGGAAAACAACGAG GGCAGGCGGAGCAAG

AGAGGCGCCAGAAGGCTGAAGCGGCGGAGGCGGCATAGAATCCAGAGAGTGAAGAAG CTGCTGTTCGACTAC

AACCTGCTGACCGACCACAGCGAGCTGAGCGGCATCAACCCCTACGAGGCCAGAGTG AAGGGCCTGAGCCAG

AAGCTGAGCGAGGAAGAGTTCTCTGCCGCCCTGCTGCACCTGGCCAAGAGAAGAGGC GTGCACAACGTGAACG

AGGTGGAAGAGGACACCGGCAACGAGCTGTCCACCAAAGAGCAGATCAGCCGGAACA GCAAGGCCCTGGAAG

AGAAATACGTGGCCGAACTGCAGCTGGAACGGCTGAAGAAAGACGGCGAAGTGCGGG GCAGCATCAACAGATT

CAAGACCAGCGACTACGTGAAAGAAGCCAAACAGCTGCTGAAGGTGCAGAAGGCCTA CCACCAGCTGGACCAG

AGCTTCATCGACACCTACATCGACCTGCTGGAAACCCGGCGGACCTACTATGAGGGA CCTGGCGAGGGCAGCC

CCTTCGGCTGGAAGGACATCAAAGAATGGTACGAGATGCTGATGGGCCACTGCACCT ACTTCCCCGAGGAACT

GCGGAGCGTGAAGTACGCCTACAACGCCGACCTGTACAACGCCCTGAACGACCTGAA CAATCTCGTGATCACC

AGGGACGAGAACGAGAAGCTGGAATATTACGAGAAGTTCCAGATCATCGAGAACGTG TTCAAGCAGAAGAAGAA

GCCCACCCTGAAGCAGATCGCCAAAGAAATCCTCGTGAACGAAGAGGATATTAAGGG CTACAGAGTGACCAGCA

CCGGCAAGCCCGAGTTCACCAACCTGAAGGTGTACCACGACATCAAGGACATTACCG CCCGGAAAGAGATTATT

GAGAACGCCGAGCTGCTGGATCAGATTGCCAAGATCCTGACCATCTACCAGAGCAGC GAGGACATCCAGGAAG

AACTGACCAATCTGAACTCCGAGCTGACCCAGGAAGAGATCGAGCAGATCTCTAATC TGAAGGGCTATACCGGC ACCCACAACCTGAGCCTGAAGGCCATCAACCTGATCCTGGACGAGCTGTGGCACACCAAC GACAACCAGATCG

CTATCTTCAACCGGCTGAAGCTGGTGCCCAAGAAGGTGGACCTGTCCCAGCAGAAAG AGATCCCCACCACCCT

GGTGGACGACTTCATCCTGAGCCCCGTCGTGAAGAGAAGCTTCATCCAGAGCATCAA AGTGATCAACGCCATCA

TCAAGAAGTACGGCCTGCCCAACGACATCATTATCGAGCTGGCCCGCGAGAAGAACT CCAAGGACGCCCAGAA

AATGATCAACGAGATGCAGAAGCGGAACCGGCAGACCAACGAGCGGATCGAGGAAAT CATCCGGACCACCGGC

AAAGAGAACGCCAAGTACCTGATCGAGAAGATCAAGCTGCACGACATGCAGGAAGGC AAGTGCCTGTACAGCC

TGGAAGCCATCCCTCTGGAAGATCTGCTGAACAACCCCTTCAACTATGAGGTGGACC ACATCATCCCCAGAAGC

GTGTCCTTCGACAACAGCTTCAACAACAAGGTGCTCGTGAAGCAGGAAGAAGCCAGC AAGAAGGGCAACCGGA

CCCCATTCCAGTACCTGAGCAGCAGCGACAGCAAGATCAGCTACGAAACCTTCAAGA AGCACATCCTGAATCTG

GCCAAGGGCAAGGGCAGAATCAGCAAGACCAAGAAAGAGTATCTGCTGGAAGAACGG GACATCAACAGGTTCT

CCGTGCAGAAAGACTTCATCAACCGGAACCTGGTGGATACCAGATACGCCACCAGAG GCCTGATGAACCTGCT

GCGGAGCTACTTCAGAGTGAACAACCTGGACGTGAAAGTGAAGTCCATCAATGGCGG CTTCACCAGCTTTCTGC

GGCGGAAGTGGAAGTTTAAGAAAGAGCGGAACAAGGGGTACAAGCACCACGCCGAGG ACGCCCTGATCATTGC

CAACGCCGATTTCATCTTCAAAGAGTGGAAGAAACTGGACAAGGCCAAAAAAGTGAT GGAAAACCAGATGTTCG

AGGAAAAGCAGGCCGAGAGCATGCCCGAGATCGAAACCGAGCAGGAGTACAAAGAGA TCTTCATCACCCCCCA

CCAGATCAAGCACATTAAGGACTTCAAGGACTACAAGTACAGCCACCGGGTGGACAA GAAGCCTAATAGAGAGC

TGATTAACGACACCCTGTACTCCACCCGGAAGGACGACAAGGGCAACACCCTGATCG TGAACAATCTGAACGGC

CTGTACGACAAGGACAATGACAAGCTGAAAAAGCTGATCAACAAGAGCCCCGAAAAG CTGCTGATGTACCACCA

CGACCCCCAGACCTACCAGAAACTGAAGCTGATTATGGAACAGTACGGCGACGAGAA GAATCCCCTGTACAAGT

ACTACGAGGAAACCGGGAACTACCTGACCAAGTACTCCAAAAAGGACAACGGCCCCG TGATCAAGAAGATTAAG

TATTACGGCAACAAACTGAACGCCCATCTGGACATCACCGACGACTACCCCAACAGC AGAAACAAGGTCGTGAA

GCTGTCCCTGAAGCCCTACAGATTCGACGTGTACCTGGACAATGGCGTGTACAAGTT CGTGACCGTGAAGAATC

TGGATGTGATCAAAAAAGAAAACTACTACGAAGTGAATAGCAAGTGCTATGAGGAAG CTAAGAAGCTGAAGAAGA

TCAGCAACCAGGCCGAGTTTATCGCCTCCTTCTACAACAACGATCTGATCAAGATCA ACGGCGAGCTGTATAGA

GTGATCGGCGTGAACAACGACCTGCTGAACCGGATCGAAGTGAACATGATCGACATC ACCTACCGCGAGTACCT

GGAAAACATGAACGACAAGAGGCCCCCCAGGATCATTAAGACAATCGCCTCCAAGAC CCAGAGCATTAAGAAGT

ACAGCACAGACATTCTGGGCAACCTGTATGAAGTGAAATCTAAGAAGCACCCTCAGA TCATCAAAAAGGGCAAAA

GGCCGGCGGCCACGAAAAAGGCCGGCCAGGCAAAAAAGAAAAAGGGATCCGGACGGG CTGACGCATTGGACG

ATTTTGATCTGGATATGCTGGGAAGTGACGCCCTCGATGATTTTGACCTTGACATGC TTGGTTCGGATGCCCTTG

ATGACTTTGACCTCGACATGCTCGGCAGTGACGCCCTTGATGATTTCGACCTGGACA TGCTGATTAACTGTACAG

GCAGTGGAGAGGGCAGAGGAAGTCTGCTAACATGCGGTGACGTCGAGGAGAATCCTG GCCCAATGGCCAAGC

CTTTGTCTCAAGAAGAATCCACCCTCATTGAAAGAGCAACGGCTACAATCAACAGCA TCCCCATCTCTGAAGACT

ACAGCGTCGCCAGCGCAGCTCTCTCTAGCGACGGCCGCATCTTCACTGGTGTCAATG TATATCATTTTACTGGG

GGACCTTGTGCAGAACTCGTGGTGCTGGGCACTGCTGCTGCTGCGGCAGCTGGCAAC CTGACTTGTATCGTCG

CGATCGGAAATGAGAACAGGGGCATCTTGAGCCCCTGCGGACGGTGCCGACAGGTGC TTCTCGATCTGCATCC

TGGGATCAAAGCCATAGTGAAGGACAGTGATGGACAGCCGACGGCAGTTGGGATTCG TGAATTGCTGCCCTCT

GGTTATGTGTGGGAGGGCTAAGAATTCCTAGAGCTCGCTGATCAGCCTCGACTGTGC CTTCTAGTTGCCAGCCA

TCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACT GTCCTTTCCTAATAAAAT

GAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTG GGGCAGGACAGCAAGG

GGGAGGATTGGGAAGAGAATAGCAGGCATGCTGGGGAGGTACCGAGGGCCTATTTCC CATGATTCCTTCATATT

TGCATATACGATACAAGGCTGTTAGAGAGATAATTGGAATTAATTTGACTGTAAACA CAAAGATATTAGTACAAAA

TACGTGACGTAGAAAGTAATAATTTCTTGGGTAGTTTGCAGTTTTAAAATTATGTTT TAAAATGGACTATCATATGC

TTACCGTAACTTGAAAGTATTTCGATTTCTTGGCTTTATATATCTTGTGGAAAGGAC GAAAcaccGCCCGCAGCGAA

CTCGAATTAAgTTTTAGTACTCTGGAAACAGAATCTACTAAAACAAGGCAAAATGCC GTGTTTATCTCGTCAACTT

GTTGGCGAGATTTTTGCGGCCGCAGGAACCCCTAGTGATGGAGTTGGCCACTCCCTC TCTGCGCGCTCGCTCG

CTCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGGGCTTTGCCCGGGCGGCC TCAGTGAGCGAGCG

AGCGCGCAGCTGCCTGCAGGGGCGCCTGATGCGGTATTTTCTCCTTACGCATCTGTG CGGTATTTCACACCGCA

TACGTCAAAGCAACCATAGTACGCGCCCTGTAGCGGCGCATTAAGCGCGGCGGGTGT GGTGGTTACGCGCAGC

GTGACCGCTACACTTGCCAGCGCCTTAGCGCCCGCTCCTTTCGCTTTCTTCCCTTCC TTTCTCGCCACGTTCGC

CGGCTTTCCCCGTCAAGCTCTAAATCGGGGGCTCCCTTTAGGGTTCCGATTTAGTGC TTTACGGCACCTCGACC

CCAAAAAACTTGATTTGGGTGATGGTTCACGTAGTGGGCCATCGCCCTGATAGACGG TTTTTCGCCCTTTGACGT

TGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAACTGGAACAACACTCAACT CTATCTCGGGCTATTCTTT

TGATTTATAAGGGATTTTGCCGATTTCGGTCTATTGGTTAAAAAATGAGCTGATTTA ACAAAAATTTAACGCGAATT TTAACAAAATATTAACGTTTACAATTTTATGGTGCACTCTCAGTACAATCTGCTCTGATG CCGCATAGTTAAGCCA

GCCCCGACACCCGCCAACACCCGCTGACGCGCCCTGACGGGCTTGTCTGCTCCCGGC ATCCGCTTACAGACAA

GCTGTGACCGTCTCCGGGAGCTGCATGTGTCAGAGGTTTTCACCGTCATCACCGAAA CGCGCGAGACGAAAGG

GCCTCGTGATACGCCTATTTTTATAGGTTAATGTCATGATAATAATGGTTTCTTAGA CGTCAGGTGGCACTTTTCG

GGGAAATGTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTA TCCGCTCATGAGACAATAA

CCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTC CGTGTCGCCCTTATTCCCT

TTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAA AAGATGCTGAAGATCAGTT

GGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAG TTTTCGCCCCGAAGAAC

GTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTA TTGACGCCGGGCAAGAGC

AACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCA CAGAAAAGCATCTTACGG

ATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTG CGGCCAACTTACTTCTGA

CAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATG TAACTCGCCTTGATCGT

TGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCT GTAGCAATGGCAACAA

CGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAA TAGACTGGATGGAGGCG

GATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCT GATAAATCTGGAGCCGG

TGAGCGTGGAAGCCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCG TATCGTAGTTATCTACA

CGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTG CCTCACTGATTAAGCAT

TGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCAT TTTTAATTTAAAAGGATCTAG

GTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTC CACTGAGCGTCAGACCCC

GTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGC TTGCAAACAAAAAAACCAC

CGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGG TAACTGGCTTCAGCAGA

GCGCAGATACCAAATACTGTTCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAG AACTCTGTAGCACCGCCT

ACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCG TGTCTTACCGGGTTGGA

CTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTG CACACAGCCCAGCTTG

GAGCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCC ACGCTTCCCGAAGGGA

GAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGG AGCTTCCAGGGGGA

AACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGA TTTTTGTGATGCTCGTCA

GGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCC TTTTGCTGGCCTTTTG

CTCACATGT

1.4 LGI1

Nucleotide sequence of sasgRNA for mouse LGI1; sgRNA1 (SEQ ID NO: 69)

TGCCTGAGCGAGGAACAGCTC

Nucleotide sequence of sasgRNA for mouse LGI1; sgRNA2 (SEQ ID NO: 70)

CACTGCTGGGGGAAGAGACCT

Nucleotide sequence of sasgRNA for mouse LGI1; sgRNA3 (SEQ ID NO: 71)

GACCTGTGAGGTGCTGCGAGG pAAV-CMV-sadCas9-U6gRNA(Lgi1-sa sgRNA1) used in in vitro qPCR experiments (SEQ ID NO: 72)

CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCGTCGGGCGACC TTTGGTCGCCCGGCC

TCAGTGAGCGAGCGAGCGCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCC TGCGGCCTCTAGACTC

GAGGCGTTGACATTGATTATTGACTAGTTATTAATAGTAATCAATTACGGGGTCATT AGTTCATAGCCCATATATG

GAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGAC CCCCGCCCATTGACGT

CAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAAT GGGTGGAGTATTTACGGT

AAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTG ACGTCAATGACGGTAAAT

GGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGT ACATCTACGTATTAGTCA

TCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAATGGGCGTGGATAGCGGT TTGACTCACGGGGATTT

CCAAGTCTCCACCCCATTGACGTCAATGGGAGTTTGTTTTGGCACCAAAATCAACGG GACTTTCCAAAATGTCGT AACAACTCCGCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTATATA AGCAGAGCTCTCT

GGCTAACTACCGGTGCCACCATGGCCCCAAAGAAGAAGCGGAAGGTCGGTATCCACG GAGTCCCAGCAGCCAA

GCGGAACTACATCCTGGGCCTGGCCATCGGCATCACCAGCGTGGGCTACGGCATCAT CGACTACGAGACACGG

GACGTGATCGATGCCGGCGTGCGGCTGTTCAAAGAGGCCAACGTGGAAAACAACGAG GGCAGGCGGAGCAAG

AGAGGCGCCAGAAGGCTGAAGCGGCGGAGGCGGCATAGAATCCAGAGAGTGAAGAAG CTGCTGTTCGACTAC

AACCTGCTGACCGACCACAGCGAGCTGAGCGGCATCAACCCCTACGAGGCCAGAGTG AAGGGCCTGAGCCAG

AAGCTGAGCGAGGAAGAGTTCTCTGCCGCCCTGCTGCACCTGGCCAAGAGAAGAGGC GTGCACAACGTGAACG

AGGTGGAAGAGGACACCGGCAACGAGCTGTCCACCAAAGAGCAGATCAGCCGGAACA GCAAGGCCCTGGAAG

AGAAATACGTGGCCGAACTGCAGCTGGAACGGCTGAAGAAAGACGGCGAAGTGCGGG GCAGCATCAACAGATT

CAAGACCAGCGACTACGTGAAAGAAGCCAAACAGCTGCTGAAGGTGCAGAAGGCCTA CCACCAGCTGGACCAG

AGCTTCATCGACACCTACATCGACCTGCTGGAAACCCGGCGGACCTACTATGAGGGA CCTGGCGAGGGCAGCC

CCTTCGGCTGGAAGGACATCAAAGAATGGTACGAGATGCTGATGGGCCACTGCACCT ACTTCCCCGAGGAACT

GCGGAGCGTGAAGTACGCCTACAACGCCGACCTGTACAACGCCCTGAACGACCTGAA CAATCTCGTGATCACC

AGGGACGAGAACGAGAAGCTGGAATATTACGAGAAGTTCCAGATCATCGAGAACGTG TTCAAGCAGAAGAAGAA

GCCCACCCTGAAGCAGATCGCCAAAGAAATCCTCGTGAACGAAGAGGATATTAAGGG CTACAGAGTGACCAGCA

CCGGCAAGCCCGAGTTCACCAACCTGAAGGTGTACCACGACATCAAGGACATTACCG CCCGGAAAGAGATTATT

GAGAACGCCGAGCTGCTGGATCAGATTGCCAAGATCCTGACCATCTACCAGAGCAGC GAGGACATCCAGGAAG

AACTGACCAATCTGAACTCCGAGCTGACCCAGGAAGAGATCGAGCAGATCTCTAATC TGAAGGGCTATACCGGC

ACCCACAACCTGAGCCTGAAGGCCATCAACCTGATCCTGGACGAGCTGTGGCACACC AACGACAACCAGATCG

CTATCTTCAACCGGCTGAAGCTGGTGCCCAAGAAGGTGGACCTGTCCCAGCAGAAAG AGATCCCCACCACCCT

GGTGGACGACTTCATCCTGAGCCCCGTCGTGAAGAGAAGCTTCATCCAGAGCATCAA AGTGATCAACGCCATCA

TCAAGAAGTACGGCCTGCCCAACGACATCATTATCGAGCTGGCCCGCGAGAAGAACT CCAAGGACGCCCAGAA

AATGATCAACGAGATGCAGAAGCGGAACCGGCAGACCAACGAGCGGATCGAGGAAAT CATCCGGACCACCGGC

AAAGAGAACGCCAAGTACCTGATCGAGAAGATCAAGCTGCACGACATGCAGGAAGGC AAGTGCCTGTACAGCC

TGGAAGCCATCCCTCTGGAAGATCTGCTGAACAACCCCTTCAACTATGAGGTGGACC ACATCATCCCCAGAAGC

GTGTCCTTCGACAACAGCTTCAACAACAAGGTGCTCGTGAAGCAGGAAGAAGCCAGC AAGAAGGGCAACCGGA

CCCCATTCCAGTACCTGAGCAGCAGCGACAGCAAGATCAGCTACGAAACCTTCAAGA AGCACATCCTGAATCTG

GCCAAGGGCAAGGGCAGAATCAGCAAGACCAAGAAAGAGTATCTGCTGGAAGAACGG GACATCAACAGGTTCT

CCGTGCAGAAAGACTTCATCAACCGGAACCTGGTGGATACCAGATACGCCACCAGAG GCCTGATGAACCTGCT

GCGGAGCTACTTCAGAGTGAACAACCTGGACGTGAAAGTGAAGTCCATCAATGGCGG CTTCACCAGCTTTCTGC

GGCGGAAGTGGAAGTTTAAGAAAGAGCGGAACAAGGGGTACAAGCACCACGCCGAGG ACGCCCTGATCATTGC

CAACGCCGATTTCATCTTCAAAGAGTGGAAGAAACTGGACAAGGCCAAAAAAGTGAT GGAAAACCAGATGTTCG

AGGAAAAGCAGGCCGAGAGCATGCCCGAGATCGAAACCGAGCAGGAGTACAAAGAGA TCTTCATCACCCCCCA

CCAGATCAAGCACATTAAGGACTTCAAGGACTACAAGTACAGCCACCGGGTGGACAA GAAGCCTAATAGAGAGC

TGATTAACGACACCCTGTACTCCACCCGGAAGGACGACAAGGGCAACACCCTGATCG TGAACAATCTGAACGGC

CTGTACGACAAGGACAATGACAAGCTGAAAAAGCTGATCAACAAGAGCCCCGAAAAG CTGCTGATGTACCACCA

CGACCCCCAGACCTACCAGAAACTGAAGCTGATTATGGAACAGTACGGCGACGAGAA GAATCCCCTGTACAAGT

ACTACGAGGAAACCGGGAACTACCTGACCAAGTACTCCAAAAAGGACAACGGCCCCG TGATCAAGAAGATTAAG

TATTACGGCAACAAACTGAACGCCCATCTGGACATCACCGACGACTACCCCAACAGC AGAAACAAGGTCGTGAA

GCTGTCCCTGAAGCCCTACAGATTCGACGTGTACCTGGACAATGGCGTGTACAAGTT CGTGACCGTGAAGAATC

TGGATGTGATCAAAAAAGAAAACTACTACGAAGTGAATAGCAAGTGCTATGAGGAAG CTAAGAAGCTGAAGAAGA

TCAGCAACCAGGCCGAGTTTATCGCCTCCTTCTACAACAACGATCTGATCAAGATCA ACGGCGAGCTGTATAGA

GTGATCGGCGTGAACAACGACCTGCTGAACCGGATCGAAGTGAACATGATCGACATC ACCTACCGCGAGTACCT

GGAAAACATGAACGACAAGAGGCCCCCCAGGATCATTAAGACAATCGCCTCCAAGAC CCAGAGCATTAAGAAGT

ACAGCACAGACATTCTGGGCAACCTGTATGAAGTGAAATCTAAGAAGCACCCTCAGA TCATCAAAAAGGGCAAAA

GGCCGGCGGCCACGAAAAAGGCCGGCCAGGCAAAAAAGAAAAAGGGATCCGGACGGG CTGACGCATTGGACG

ATTTTGATCTGGATATGCTGGGAAGTGACGCCCTCGATGATTTTGACCTTGACATGC TTGGTTCGGATGCCCTTG

ATGACTTTGACCTCGACATGCTCGGCAGTGACGCCCTTGATGATTTCGACCTGGACA TGCTGATTAACTGTACAG

GCAGTGGAGAGGGCAGAGGAAGTCTGCTAACATGCGGTGACGTCGAGGAGAATCCTG GCCCAATGGCCAAGC

CTTTGTCTCAAGAAGAATCCACCCTCATTGAAAGAGCAACGGCTACAATCAACAGCA TCCCCATCTCTGAAGACT

ACAGCGTCGCCAGCGCAGCTCTCTCTAGCGACGGCCGCATCTTCACTGGTGTCAATG TATATCATTTTACTGGG

GGACCTTGTGCAGAACTCGTGGTGCTGGGCACTGCTGCTGCTGCGGCAGCTGGCAAC CTGACTTGTATCGTCG

CGATCGGAAATGAGAACAGGGGCATCTTGAGCCCCTGCGGACGGTGCCGACAGGTGC TTCTCGATCTGCATCC TGGGATCAAAGCCATAGTGAAGGACAGTGATGGACAGCCGACGGCAGTTGGGATTCGTGA ATTGCTGCCCTCT

GGTTATGTGTGGGAGGGCTAAGAATTCCTAGAGCTCGCTGATCAGCCTCGACTGTGC CTTCTAGTTGCCAGCCA

TCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACT GTCCTTTCCTAATAAAAT

GAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTG GGGCAGGACAGCAAGG

GGGAGGATTGGGAAGAGAATAGCAGGCATGCTGGGGAGGTACCGAGGGCCTATTTCC CATGATTCCTTCATATT

TGCATATACGATACAAGGCTGTTAGAGAGATAATTGGAATTAATTTGACTGTAAACA CAAAGATATTAGTACAAAA

TACGTGACGTAGAAAGTAATAATTTCTTGGGTAGTTTGCAGTTTTAAAATTATGTTT TAAAATGGACTATCATATGC

TTACCGTAACTTGAAAGTATTTCGATTTCTTGGCTTTATATATCTTGTGGAAAGGAC GAAAcaccgTGCCTGAGCGA

GGAACAGCTCgTTTTAGTACTCTGGAAACAGAATCTACTAAAACAAGGCAAAATGCC GTGTTTATCTCGTCAACTT

GTTGGCGAGATTTTTGCGGCCGCAGGAACCCCTAGTGATGGAGTTGGCCACTCCCTC TCTGCGCGCTCGCTCG

CTCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGGGCTTTGCCCGGGCGGCC TCAGTGAGCGAGCG

AGCGCGCAGCTGCCTGCAGGGGCGCCTGATGCGGTATTTTCTCCTTACGCATCTGTG CGGTATTTCACACCGCA

TACGTCAAAGCAACCATAGTACGCGCCCTGTAGCGGCGCATTAAGCGCGGCGGGTGT GGTGGTTACGCGCAGC

GTGACCGCTACACTTGCCAGCGCCTTAGCGCCCGCTCCTTTCGCTTTCTTCCCTTCC TTTCTCGCCACGTTCGC

CGGCTTTCCCCGTCAAGCTCTAAATCGGGGGCTCCCTTTAGGGTTCCGATTTAGTGC TTTACGGCACCTCGACC

CCAAAAAACTTGATTTGGGTGATGGTTCACGTAGTGGGCCATCGCCCTGATAGACGG TTTTTCGCCCTTTGACGT

TGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAACTGGAACAACACTCAACT CTATCTCGGGCTATTCTTT

TGATTTATAAGGGATTTTGCCGATTTCGGTCTATTGGTTAAAAAATGAGCTGATTTA ACAAAAATTTAACGCGAATT

TTAACAAAATATTAACGTTTACAATTTTATGGTGCACTCTCAGTACAATCTGCTCTG ATGCCGCATAGTTAAGCCA

GCCCCGACACCCGCCAACACCCGCTGACGCGCCCTGACGGGCTTGTCTGCTCCCGGC ATCCGCTTACAGACAA

GCTGTGACCGTCTCCGGGAGCTGCATGTGTCAGAGGTTTTCACCGTCATCACCGAAA CGCGCGAGACGAAAGG

GCCTCGTGATACGCCTATTTTTATAGGTTAATGTCATGATAATAATGGTTTCTTAGA CGTCAGGTGGCACTTTTCG

GGGAAATGTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTA TCCGCTCATGAGACAATAA

CCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTC CGTGTCGCCCTTATTCCCT

TTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAA AAGATGCTGAAGATCAGTT

GGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAG TTTTCGCCCCGAAGAAC

GTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTA TTGACGCCGGGCAAGAGC

AACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCA CAGAAAAGCATCTTACGG

ATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTG CGGCCAACTTACTTCTGA

CAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATG TAACTCGCCTTGATCGT

TGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCT GTAGCAATGGCAACAA

CGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAA TAGACTGGATGGAGGCG

GATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCT GATAAATCTGGAGCCGG

TGAGCGTGGAAGCCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCG TATCGTAGTTATCTACA

CGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTG CCTCACTGATTAAGCAT

TGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCAT TTTTAATTTAAAAGGATCTAG

GTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTC CACTGAGCGTCAGACCCC

GTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGC TTGCAAACAAAAAAACCAC

CGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGG TAACTGGCTTCAGCAGA

GCGCAGATACCAAATACTGTTCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAG AACTCTGTAGCACCGCCT

ACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCG TGTCTTACCGGGTTGGA

CTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTG CACACAGCCCAGCTTG

GAGCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCC ACGCTTCCCGAAGGGA

GAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGG AGCTTCCAGGGGGA

AACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGA TTTTTGTGATGCTCGTCA

GGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCC TTTTGCTGGCCTTTTG CTCACATGT pAAV-CMV-sadCas9-U6gRNA(Lgi1-sa sgRNA2) used in in vitro qPCR experiments (SEQ ID NO: 73)

CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCGTCGGGCGACC TTTGGTCGCCCGGCC

TCAGTGAGCGAGCGAGCGCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCC TGCGGCCTCTAGACTC

GAGGCGTTGACATTGATTATTGACTAGTTATTAATAGTAATCAATTACGGGGTCATT AGTTCATAGCCCATATATG

GAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGAC CCCCGCCCATTGACGT CAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGG TGGAGTATTTACGGT

AAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTG ACGTCAATGACGGTAAAT

GGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGT ACATCTACGTATTAGTCA

TCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAATGGGCGTGGATAGCGGT TTGACTCACGGGGATTT

CCAAGTCTCCACCCCATTGACGTCAATGGGAGTTTGTTTTGGCACCAAAATCAACGG GACTTTCCAAAATGTCGT

AACAACTCCGCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTAT ATAAGCAGAGCTCTCT

GGCTAACTACCGGTGCCACCATGGCCCCAAAGAAGAAGCGGAAGGTCGGTATCCACG GAGTCCCAGCAGCCAA

GCGGAACTACATCCTGGGCCTGGCCATCGGCATCACCAGCGTGGGCTACGGCATCAT CGACTACGAGACACGG

GACGTGATCGATGCCGGCGTGCGGCTGTTCAAAGAGGCCAACGTGGAAAACAACGAG GGCAGGCGGAGCAAG

AGAGGCGCCAGAAGGCTGAAGCGGCGGAGGCGGCATAGAATCCAGAGAGTGAAGAAG CTGCTGTTCGACTAC

AACCTGCTGACCGACCACAGCGAGCTGAGCGGCATCAACCCCTACGAGGCCAGAGTG AAGGGCCTGAGCCAG

AAGCTGAGCGAGGAAGAGTTCTCTGCCGCCCTGCTGCACCTGGCCAAGAGAAGAGGC GTGCACAACGTGAACG

AGGTGGAAGAGGACACCGGCAACGAGCTGTCCACCAAAGAGCAGATCAGCCGGAACA GCAAGGCCCTGGAAG

AGAAATACGTGGCCGAACTGCAGCTGGAACGGCTGAAGAAAGACGGCGAAGTGCGGG GCAGCATCAACAGATT

CAAGACCAGCGACTACGTGAAAGAAGCCAAACAGCTGCTGAAGGTGCAGAAGGCCTA CCACCAGCTGGACCAG

AGCTTCATCGACACCTACATCGACCTGCTGGAAACCCGGCGGACCTACTATGAGGGA CCTGGCGAGGGCAGCC

CCTTCGGCTGGAAGGACATCAAAGAATGGTACGAGATGCTGATGGGCCACTGCACCT ACTTCCCCGAGGAACT

GCGGAGCGTGAAGTACGCCTACAACGCCGACCTGTACAACGCCCTGAACGACCTGAA CAATCTCGTGATCACC

AGGGACGAGAACGAGAAGCTGGAATATTACGAGAAGTTCCAGATCATCGAGAACGTG TTCAAGCAGAAGAAGAA

GCCCACCCTGAAGCAGATCGCCAAAGAAATCCTCGTGAACGAAGAGGATATTAAGGG CTACAGAGTGACCAGCA

CCGGCAAGCCCGAGTTCACCAACCTGAAGGTGTACCACGACATCAAGGACATTACCG CCCGGAAAGAGATTATT

GAGAACGCCGAGCTGCTGGATCAGATTGCCAAGATCCTGACCATCTACCAGAGCAGC GAGGACATCCAGGAAG

AACTGACCAATCTGAACTCCGAGCTGACCCAGGAAGAGATCGAGCAGATCTCTAATC TGAAGGGCTATACCGGC

ACCCACAACCTGAGCCTGAAGGCCATCAACCTGATCCTGGACGAGCTGTGGCACACC AACGACAACCAGATCG

CTATCTTCAACCGGCTGAAGCTGGTGCCCAAGAAGGTGGACCTGTCCCAGCAGAAAG AGATCCCCACCACCCT

GGTGGACGACTTCATCCTGAGCCCCGTCGTGAAGAGAAGCTTCATCCAGAGCATCAA AGTGATCAACGCCATCA

TCAAGAAGTACGGCCTGCCCAACGACATCATTATCGAGCTGGCCCGCGAGAAGAACT CCAAGGACGCCCAGAA

AATGATCAACGAGATGCAGAAGCGGAACCGGCAGACCAACGAGCGGATCGAGGAAAT CATCCGGACCACCGGC

AAAGAGAACGCCAAGTACCTGATCGAGAAGATCAAGCTGCACGACATGCAGGAAGGC AAGTGCCTGTACAGCC

TGGAAGCCATCCCTCTGGAAGATCTGCTGAACAACCCCTTCAACTATGAGGTGGACC ACATCATCCCCAGAAGC

GTGTCCTTCGACAACAGCTTCAACAACAAGGTGCTCGTGAAGCAGGAAGAAGCCAGC AAGAAGGGCAACCGGA

CCCCATTCCAGTACCTGAGCAGCAGCGACAGCAAGATCAGCTACGAAACCTTCAAGA AGCACATCCTGAATCTG

GCCAAGGGCAAGGGCAGAATCAGCAAGACCAAGAAAGAGTATCTGCTGGAAGAACGG GACATCAACAGGTTCT

CCGTGCAGAAAGACTTCATCAACCGGAACCTGGTGGATACCAGATACGCCACCAGAG GCCTGATGAACCTGCT

GCGGAGCTACTTCAGAGTGAACAACCTGGACGTGAAAGTGAAGTCCATCAATGGCGG CTTCACCAGCTTTCTGC

GGCGGAAGTGGAAGTTTAAGAAAGAGCGGAACAAGGGGTACAAGCACCACGCCGAGG ACGCCCTGATCATTGC

CAACGCCGATTTCATCTTCAAAGAGTGGAAGAAACTGGACAAGGCCAAAAAAGTGAT GGAAAACCAGATGTTCG

AGGAAAAGCAGGCCGAGAGCATGCCCGAGATCGAAACCGAGCAGGAGTACAAAGAGA TCTTCATCACCCCCCA

CCAGATCAAGCACATTAAGGACTTCAAGGACTACAAGTACAGCCACCGGGTGGACAA GAAGCCTAATAGAGAGC

TGATTAACGACACCCTGTACTCCACCCGGAAGGACGACAAGGGCAACACCCTGATCG TGAACAATCTGAACGGC

CTGTACGACAAGGACAATGACAAGCTGAAAAAGCTGATCAACAAGAGCCCCGAAAAG CTGCTGATGTACCACCA

CGACCCCCAGACCTACCAGAAACTGAAGCTGATTATGGAACAGTACGGCGACGAGAA GAATCCCCTGTACAAGT

ACTACGAGGAAACCGGGAACTACCTGACCAAGTACTCCAAAAAGGACAACGGCCCCG TGATCAAGAAGATTAAG

TATTACGGCAACAAACTGAACGCCCATCTGGACATCACCGACGACTACCCCAACAGC AGAAACAAGGTCGTGAA

GCTGTCCCTGAAGCCCTACAGATTCGACGTGTACCTGGACAATGGCGTGTACAAGTT CGTGACCGTGAAGAATC

TGGATGTGATCAAAAAAGAAAACTACTACGAAGTGAATAGCAAGTGCTATGAGGAAG CTAAGAAGCTGAAGAAGA

TCAGCAACCAGGCCGAGTTTATCGCCTCCTTCTACAACAACGATCTGATCAAGATCA ACGGCGAGCTGTATAGA

GTGATCGGCGTGAACAACGACCTGCTGAACCGGATCGAAGTGAACATGATCGACATC ACCTACCGCGAGTACCT

GGAAAACATGAACGACAAGAGGCCCCCCAGGATCATTAAGACAATCGCCTCCAAGAC CCAGAGCATTAAGAAGT

ACAGCACAGACATTCTGGGCAACCTGTATGAAGTGAAATCTAAGAAGCACCCTCAGA TCATCAAAAAGGGCAAAA

GGCCGGCGGCCACGAAAAAGGCCGGCCAGGCAAAAAAGAAAAAGGGATCCGGACGGG CTGACGCATTGGACG

ATTTTGATCTGGATATGCTGGGAAGTGACGCCCTCGATGATTTTGACCTTGACATGC TTGGTTCGGATGCCCTTG

ATGACTTTGACCTCGACATGCTCGGCAGTGACGCCCTTGATGATTTCGACCTGGACA TGCTGATTAACTGTACAG GCAGTGGAGAGGGCAGAGGAAGTCTGCTAACATGCGGTGACGTCGAGGAGAATCCTGGCC CAATGGCCAAGC

CTTTGTCTCAAGAAGAATCCACCCTCATTGAAAGAGCAACGGCTACAATCAACAGCA TCCCCATCTCTGAAGACT

ACAGCGTCGCCAGCGCAGCTCTCTCTAGCGACGGCCGCATCTTCACTGGTGTCAATG TATATCATTTTACTGGG

GGACCTTGTGCAGAACTCGTGGTGCTGGGCACTGCTGCTGCTGCGGCAGCTGGCAAC CTGACTTGTATCGTCG

CGATCGGAAATGAGAACAGGGGCATCTTGAGCCCCTGCGGACGGTGCCGACAGGTGC TTCTCGATCTGCATCC

TGGGATCAAAGCCATAGTGAAGGACAGTGATGGACAGCCGACGGCAGTTGGGATTCG TGAATTGCTGCCCTCT

GGTTATGTGTGGGAGGGCTAAGAATTCCTAGAGCTCGCTGATCAGCCTCGACTGTGC CTTCTAGTTGCCAGCCA

TCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACT GTCCTTTCCTAATAAAAT

GAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTG GGGCAGGACAGCAAGG

GGGAGGATTGGGAAGAGAATAGCAGGCATGCTGGGGAGGTACCGAGGGCCTATTTCC CATGATTCCTTCATATT

TGCATATACGATACAAGGCTGTTAGAGAGATAATTGGAATTAATTTGACTGTAAACA CAAAGATATTAGTACAAAA

TACGTGACGTAGAAAGTAATAATTTCTTGGGTAGTTTGCAGTTTTAAAATTATGTTT TAAAATGGACTATCATATGC

TTACCGTAACTTGAAAGTATTTCGATTTCTTGGCTTTATATATCTTGTGGAAAGGAC GAAAcaccgCACTGCTGGGG

GAAGAGACCTgTTTTAGTACTCTGGAAACAGAATCTACTAAAACAAGGCAAAATGCC GTGTTTATCTCGTCAACTT

GTTGGCGAGATTTTTGCGGCCGCAGGAACCCCTAGTGATGGAGTTGGCCACTCCCTC TCTGCGCGCTCGCTCG

CTCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGGGCTTTGCCCGGGCGGCC TCAGTGAGCGAGCG

AGCGCGCAGCTGCCTGCAGGGGCGCCTGATGCGGTATTTTCTCCTTACGCATCTGTG CGGTATTTCACACCGCA

TACGTCAAAGCAACCATAGTACGCGCCCTGTAGCGGCGCATTAAGCGCGGCGGGTGT GGTGGTTACGCGCAGC

GTGACCGCTACACTTGCCAGCGCCTTAGCGCCCGCTCCTTTCGCTTTCTTCCCTTCC TTTCTCGCCACGTTCGC

CGGCTTTCCCCGTCAAGCTCTAAATCGGGGGCTCCCTTTAGGGTTCCGATTTAGTGC TTTACGGCACCTCGACC

CCAAAAAACTTGATTTGGGTGATGGTTCACGTAGTGGGCCATCGCCCTGATAGACGG TTTTTCGCCCTTTGACGT

TGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAACTGGAACAACACTCAACT CTATCTCGGGCTATTCTTT

TGATTTATAAGGGATTTTGCCGATTTCGGTCTATTGGTTAAAAAATGAGCTGATTTA ACAAAAATTTAACGCGAATT

TTAACAAAATATTAACGTTTACAATTTTATGGTGCACTCTCAGTACAATCTGCTCTG ATGCCGCATAGTTAAGCCA

GCCCCGACACCCGCCAACACCCGCTGACGCGCCCTGACGGGCTTGTCTGCTCCCGGC ATCCGCTTACAGACAA

GCTGTGACCGTCTCCGGGAGCTGCATGTGTCAGAGGTTTTCACCGTCATCACCGAAA CGCGCGAGACGAAAGG

GCCTCGTGATACGCCTATTTTTATAGGTTAATGTCATGATAATAATGGTTTCTTAGA CGTCAGGTGGCACTTTTCG

GGGAAATGTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTA TCCGCTCATGAGACAATAA

CCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTC CGTGTCGCCCTTATTCCCT

TTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAA AAGATGCTGAAGATCAGTT

GGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAG TTTTCGCCCCGAAGAAC

GTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTA TTGACGCCGGGCAAGAGC

AACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCA CAGAAAAGCATCTTACGG

ATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTG CGGCCAACTTACTTCTGA

CAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATG TAACTCGCCTTGATCGT

TGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCT GTAGCAATGGCAACAA

CGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAA TAGACTGGATGGAGGCG

GATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCT GATAAATCTGGAGCCGG

TGAGCGTGGAAGCCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCG TATCGTAGTTATCTACA

CGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTG CCTCACTGATTAAGCAT

TGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCAT TTTTAATTTAAAAGGATCTAG

GTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTC CACTGAGCGTCAGACCCC

GTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGC TTGCAAACAAAAAAACCAC

CGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGG TAACTGGCTTCAGCAGA

GCGCAGATACCAAATACTGTTCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAG AACTCTGTAGCACCGCCT

ACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCG TGTCTTACCGGGTTGGA

CTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTG CACACAGCCCAGCTTG

GAGCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCC ACGCTTCCCGAAGGGA

GAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGG AGCTTCCAGGGGGA

AACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGA TTTTTGTGATGCTCGTCA

GGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCC TTTTGCTGGCCTTTTG

CTCACATGT pAAV-CMV-sadCas9-U6gRNA(Lgi1-sa sgRNA3) used in in vitro qPCR experiments (SEQ ID NO: 74)

CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCGTCGGGCGACC TTTGGTCGCCCGGCC

TCAGTGAGCGAGCGAGCGCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCC TGCGGCCTCTAGACTC

GAGGCGTTGACATTGATTATTGACTAGTTATTAATAGTAATCAATTACGGGGTCATT AGTTCATAGCCCATATATG

GAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGAC CCCCGCCCATTGACGT

CAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAAT GGGTGGAGTATTTACGGT

AAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTG ACGTCAATGACGGTAAAT

GGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGT ACATCTACGTATTAGTCA

TCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAATGGGCGTGGATAGCGGT TTGACTCACGGGGATTT

CCAAGTCTCCACCCCATTGACGTCAATGGGAGTTTGTTTTGGCACCAAAATCAACGG GACTTTCCAAAATGTCGT

AACAACTCCGCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTAT ATAAGCAGAGCTCTCT

GGCTAACTACCGGTGCCACCATGGCCCCAAAGAAGAAGCGGAAGGTCGGTATCCACG GAGTCCCAGCAGCCAA

GCGGAACTACATCCTGGGCCTGGCCATCGGCATCACCAGCGTGGGCTACGGCATCAT CGACTACGAGACACGG

GACGTGATCGATGCCGGCGTGCGGCTGTTCAAAGAGGCCAACGTGGAAAACAACGAG GGCAGGCGGAGCAAG

AGAGGCGCCAGAAGGCTGAAGCGGCGGAGGCGGCATAGAATCCAGAGAGTGAAGAAG CTGCTGTTCGACTAC

AACCTGCTGACCGACCACAGCGAGCTGAGCGGCATCAACCCCTACGAGGCCAGAGTG AAGGGCCTGAGCCAG

AAGCTGAGCGAGGAAGAGTTCTCTGCCGCCCTGCTGCACCTGGCCAAGAGAAGAGGC GTGCACAACGTGAACG

AGGTGGAAGAGGACACCGGCAACGAGCTGTCCACCAAAGAGCAGATCAGCCGGAACA GCAAGGCCCTGGAAG

AGAAATACGTGGCCGAACTGCAGCTGGAACGGCTGAAGAAAGACGGCGAAGTGCGGG GCAGCATCAACAGATT

CAAGACCAGCGACTACGTGAAAGAAGCCAAACAGCTGCTGAAGGTGCAGAAGGCCTA CCACCAGCTGGACCAG

AGCTTCATCGACACCTACATCGACCTGCTGGAAACCCGGCGGACCTACTATGAGGGA CCTGGCGAGGGCAGCC

CCTTCGGCTGGAAGGACATCAAAGAATGGTACGAGATGCTGATGGGCCACTGCACCT ACTTCCCCGAGGAACT

GCGGAGCGTGAAGTACGCCTACAACGCCGACCTGTACAACGCCCTGAACGACCTGAA CAATCTCGTGATCACC

AGGGACGAGAACGAGAAGCTGGAATATTACGAGAAGTTCCAGATCATCGAGAACGTG TTCAAGCAGAAGAAGAA

GCCCACCCTGAAGCAGATCGCCAAAGAAATCCTCGTGAACGAAGAGGATATTAAGGG CTACAGAGTGACCAGCA

CCGGCAAGCCCGAGTTCACCAACCTGAAGGTGTACCACGACATCAAGGACATTACCG CCCGGAAAGAGATTATT

GAGAACGCCGAGCTGCTGGATCAGATTGCCAAGATCCTGACCATCTACCAGAGCAGC GAGGACATCCAGGAAG

AACTGACCAATCTGAACTCCGAGCTGACCCAGGAAGAGATCGAGCAGATCTCTAATC TGAAGGGCTATACCGGC

ACCCACAACCTGAGCCTGAAGGCCATCAACCTGATCCTGGACGAGCTGTGGCACACC AACGACAACCAGATCG

CTATCTTCAACCGGCTGAAGCTGGTGCCCAAGAAGGTGGACCTGTCCCAGCAGAAAG AGATCCCCACCACCCT

GGTGGACGACTTCATCCTGAGCCCCGTCGTGAAGAGAAGCTTCATCCAGAGCATCAA AGTGATCAACGCCATCA

TCAAGAAGTACGGCCTGCCCAACGACATCATTATCGAGCTGGCCCGCGAGAAGAACT CCAAGGACGCCCAGAA

AATGATCAACGAGATGCAGAAGCGGAACCGGCAGACCAACGAGCGGATCGAGGAAAT CATCCGGACCACCGGC

AAAGAGAACGCCAAGTACCTGATCGAGAAGATCAAGCTGCACGACATGCAGGAAGGC AAGTGCCTGTACAGCC

TGGAAGCCATCCCTCTGGAAGATCTGCTGAACAACCCCTTCAACTATGAGGTGGACC ACATCATCCCCAGAAGC

GTGTCCTTCGACAACAGCTTCAACAACAAGGTGCTCGTGAAGCAGGAAGAAGCCAGC AAGAAGGGCAACCGGA

CCCCATTCCAGTACCTGAGCAGCAGCGACAGCAAGATCAGCTACGAAACCTTCAAGA AGCACATCCTGAATCTG

GCCAAGGGCAAGGGCAGAATCAGCAAGACCAAGAAAGAGTATCTGCTGGAAGAACGG GACATCAACAGGTTCT

CCGTGCAGAAAGACTTCATCAACCGGAACCTGGTGGATACCAGATACGCCACCAGAG GCCTGATGAACCTGCT

GCGGAGCTACTTCAGAGTGAACAACCTGGACGTGAAAGTGAAGTCCATCAATGGCGG CTTCACCAGCTTTCTGC

GGCGGAAGTGGAAGTTTAAGAAAGAGCGGAACAAGGGGTACAAGCACCACGCCGAGG ACGCCCTGATCATTGC

CAACGCCGATTTCATCTTCAAAGAGTGGAAGAAACTGGACAAGGCCAAAAAAGTGAT GGAAAACCAGATGTTCG

AGGAAAAGCAGGCCGAGAGCATGCCCGAGATCGAAACCGAGCAGGAGTACAAAGAGA TCTTCATCACCCCCCA

CCAGATCAAGCACATTAAGGACTTCAAGGACTACAAGTACAGCCACCGGGTGGACAA GAAGCCTAATAGAGAGC

TGATTAACGACACCCTGTACTCCACCCGGAAGGACGACAAGGGCAACACCCTGATCG TGAACAATCTGAACGGC

CTGTACGACAAGGACAATGACAAGCTGAAAAAGCTGATCAACAAGAGCCCCGAAAAG CTGCTGATGTACCACCA

CGACCCCCAGACCTACCAGAAACTGAAGCTGATTATGGAACAGTACGGCGACGAGAA GAATCCCCTGTACAAGT

ACTACGAGGAAACCGGGAACTACCTGACCAAGTACTCCAAAAAGGACAACGGCCCCG TGATCAAGAAGATTAAG

TATTACGGCAACAAACTGAACGCCCATCTGGACATCACCGACGACTACCCCAACAGC AGAAACAAGGTCGTGAA

GCTGTCCCTGAAGCCCTACAGATTCGACGTGTACCTGGACAATGGCGTGTACAAGTT CGTGACCGTGAAGAATC

TGGATGTGATCAAAAAAGAAAACTACTACGAAGTGAATAGCAAGTGCTATGAGGAAG CTAAGAAGCTGAAGAAGA

TCAGCAACCAGGCCGAGTTTATCGCCTCCTTCTACAACAACGATCTGATCAAGATCA ACGGCGAGCTGTATAGA

GTGATCGGCGTGAACAACGACCTGCTGAACCGGATCGAAGTGAACATGATCGACATC ACCTACCGCGAGTACCT GGAAAACATGAACGACAAGAGGCCCCCCAGGATCATTAAGACAATCGCCTCCAAGACCCA GAGCATTAAGAAGT

ACAGCACAGACATTCTGGGCAACCTGTATGAAGTGAAATCTAAGAAGCACCCTCAGA TCATCAAAAAGGGCAAAA

GGCCGGCGGCCACGAAAAAGGCCGGCCAGGCAAAAAAGAAAAAGGGATCCGGACGGG CTGACGCATTGGACG

ATTTTGATCTGGATATGCTGGGAAGTGACGCCCTCGATGATTTTGACCTTGACATGC TTGGTTCGGATGCCCTTG

ATGACTTTGACCTCGACATGCTCGGCAGTGACGCCCTTGATGATTTCGACCTGGACA TGCTGATTAACTGTACAG

GCAGTGGAGAGGGCAGAGGAAGTCTGCTAACATGCGGTGACGTCGAGGAGAATCCTG GCCCAATGGCCAAGC

CTTTGTCTCAAGAAGAATCCACCCTCATTGAAAGAGCAACGGCTACAATCAACAGCA TCCCCATCTCTGAAGACT

ACAGCGTCGCCAGCGCAGCTCTCTCTAGCGACGGCCGCATCTTCACTGGTGTCAATG TATATCATTTTACTGGG

GGACCTTGTGCAGAACTCGTGGTGCTGGGCACTGCTGCTGCTGCGGCAGCTGGCAAC CTGACTTGTATCGTCG

CGATCGGAAATGAGAACAGGGGCATCTTGAGCCCCTGCGGACGGTGCCGACAGGTGC TTCTCGATCTGCATCC

TGGGATCAAAGCCATAGTGAAGGACAGTGATGGACAGCCGACGGCAGTTGGGATTCG TGAATTGCTGCCCTCT

GGTTATGTGTGGGAGGGCTAAGAATTCCTAGAGCTCGCTGATCAGCCTCGACTGTGC CTTCTAGTTGCCAGCCA

TCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACT GTCCTTTCCTAATAAAAT

GAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTG GGGCAGGACAGCAAGG

GGGAGGATTGGGAAGAGAATAGCAGGCATGCTGGGGAGGTACCGAGGGCCTATTTCC CATGATTCCTTCATATT

TGCATATACGATACAAGGCTGTTAGAGAGATAATTGGAATTAATTTGACTGTAAACA CAAAGATATTAGTACAAAA

TACGTGACGTAGAAAGTAATAATTTCTTGGGTAGTTTGCAGTTTTAAAATTATGTTT TAAAATGGACTATCATATGC

TTACCGTAACTTGAAAGTATTTCGATTTCTTGGCTTTATATATCTTGTGGAAAGGAC GAAAcaccgACCTGTGAGGT

GCTGCGAGGgTTTTAGTACTCTGGAAACAGAATCTACTAAAACAAGGCAAAATGCCG TGTTTATCTCGTCAACTT

GTTGGCGAGATTTTTGCGGCCGCAGGAACCCCTAGTGATGGAGTTGGCCACTCCCTC TCTGCGCGCTCGCTCG

CTCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGGGCTTTGCCCGGGCGGCC TCAGTGAGCGAGCG

AGCGCGCAGCTGCCTGCAGGGGCGCCTGATGCGGTATTTTCTCCTTACGCATCTGTG CGGTATTTCACACCGCA

TACGTCAAAGCAACCATAGTACGCGCCCTGTAGCGGCGCATTAAGCGCGGCGGGTGT GGTGGTTACGCGCAGC

GTGACCGCTACACTTGCCAGCGCCTTAGCGCCCGCTCCTTTCGCTTTCTTCCCTTCC TTTCTCGCCACGTTCGC

CGGCTTTCCCCGTCAAGCTCTAAATCGGGGGCTCCCTTTAGGGTTCCGATTTAGTGC TTTACGGCACCTCGACC

CCAAAAAACTTGATTTGGGTGATGGTTCACGTAGTGGGCCATCGCCCTGATAGACGG TTTTTCGCCCTTTGACGT

TGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAACTGGAACAACACTCAACT CTATCTCGGGCTATTCTTT

TGATTTATAAGGGATTTTGCCGATTTCGGTCTATTGGTTAAAAAATGAGCTGATTTA ACAAAAATTTAACGCGAATT

TTAACAAAATATTAACGTTTACAATTTTATGGTGCACTCTCAGTACAATCTGCTCTG ATGCCGCATAGTTAAGCCA

GCCCCGACACCCGCCAACACCCGCTGACGCGCCCTGACGGGCTTGTCTGCTCCCGGC ATCCGCTTACAGACAA

GCTGTGACCGTCTCCGGGAGCTGCATGTGTCAGAGGTTTTCACCGTCATCACCGAAA CGCGCGAGACGAAAGG

GCCTCGTGATACGCCTATTTTTATAGGTTAATGTCATGATAATAATGGTTTCTTAGA CGTCAGGTGGCACTTTTCG

GGGAAATGTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTA TCCGCTCATGAGACAATAA

CCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTC CGTGTCGCCCTTATTCCCT

TTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAA AAGATGCTGAAGATCAGTT

GGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAG TTTTCGCCCCGAAGAAC

GTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTA TTGACGCCGGGCAAGAGC

AACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCA CAGAAAAGCATCTTACGG

ATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTG CGGCCAACTTACTTCTGA

CAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATG TAACTCGCCTTGATCGT

TGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCT GTAGCAATGGCAACAA

CGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAA TAGACTGGATGGAGGCG

GATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCT GATAAATCTGGAGCCGG

TGAGCGTGGAAGCCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCG TATCGTAGTTATCTACA

CGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTG CCTCACTGATTAAGCAT

TGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCAT TTTTAATTTAAAAGGATCTAG

GTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTC CACTGAGCGTCAGACCCC

GTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGC TTGCAAACAAAAAAACCAC

CGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGG TAACTGGCTTCAGCAGA

GCGCAGATACCAAATACTGTTCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAG AACTCTGTAGCACCGCCT

ACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCG TGTCTTACCGGGTTGGA

CTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTG CACACAGCCCAGCTTG

GAGCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCC ACGCTTCCCGAAGGGA GAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGGAGC TTCCAGGGGGA AACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGATTT TTGTGATGCTCGTCA GGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCCTTT TGCTGGCCTTTTG

CTCACATGT

1.5 KCNQ2

Nucleotide sequence of sasgRNA for mouse KCNQ2; sgRNA1 (SEQ ID NO: 75)

CCTCAAGGATTACCGGGCTAG

Nucleotide sequence of sasgRNA for mouse KCNQ2; sgRNA2 (SEQ ID NO: 76)

CTAGCCCGGTAATCCTTGAGG

Nucleotide of sasgRNA for mouse KCNQ2:

GGCAGGGCTGGACTCCCCCTC

Nucleotide sequence of sasgRNA for mouse KCNQ2; sgRNA4 (SEQ ID NO: 78)

CTAGCCCGGTAATCCTTGAGG

Nucleotide sequence of sasgRNA for mouse KCNQ2; sgRNA5 (SEQ ID NO: 79)

GGCAGGGCTGGACTCCCCCTC

Nucleotide sequence of sasgRNA for mouse KCNQ2; sgRNA6 (SEQ ID NO: 80)

TCCTAGCCCGGTAATCCTTGA pAAV-CMV-sadCas9-U6gRNA(Kcnq 2-sa sgRNA1) used in in vitro qPCR experiments (SEQ ID NO: 81)

CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCGTCGGGCGACC TTTGGTCGCCCGGCC

TCAGTGAGCGAGCGAGCGCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCC TGCGGCCTCTAGACTC

GAGGCGTTGACATTGATTATTGACTAGTTATTAATAGTAATCAATTACGGGGTCATT AGTTCATAGCCCATATATG

GAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGAC CCCCGCCCATTGACGT

CAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAAT GGGTGGAGTATTTACGGT

AAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTG ACGTCAATGACGGTAAAT

GGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGT ACATCTACGTATTAGTCA

TCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAATGGGCGTGGATAGCGGT TTGACTCACGGGGATTT

CCAAGTCTCCACCCCATTGACGTCAATGGGAGTTTGTTTTGGCACCAAAATCAACGG GACTTTCCAAAATGTCGT

AACAACTCCGCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTAT ATAAGCAGAGCTCTCT

GGCTAACTACCGGTGCCACCATGGCCCCAAAGAAGAAGCGGAAGGTCGGTATCCACG GAGTCCCAGCAGCCAA

GCGGAACTACATCCTGGGCCTGGCCATCGGCATCACCAGCGTGGGCTACGGCATCAT CGACTACGAGACACGG

GACGTGATCGATGCCGGCGTGCGGCTGTTCAAAGAGGCCAACGTGGAAAACAACGAG GGCAGGCGGAGCAAG

AGAGGCGCCAGAAGGCTGAAGCGGCGGAGGCGGCATAGAATCCAGAGAGTGAAGAAG CTGCTGTTCGACTAC

AACCTGCTGACCGACCACAGCGAGCTGAGCGGCATCAACCCCTACGAGGCCAGAGTG AAGGGCCTGAGCCAG

AAGCTGAGCGAGGAAGAGTTCTCTGCCGCCCTGCTGCACCTGGCCAAGAGAAGAGGC GTGCACAACGTGAACG

AGGTGGAAGAGGACACCGGCAACGAGCTGTCCACCAAAGAGCAGATCAGCCGGAACA GCAAGGCCCTGGAAG

AGAAATACGTGGCCGAACTGCAGCTGGAACGGCTGAAGAAAGACGGCGAAGTGCGGG GCAGCATCAACAGATT

CAAGACCAGCGACTACGTGAAAGAAGCCAAACAGCTGCTGAAGGTGCAGAAGGCCTA CCACCAGCTGGACCAG

AGCTTCATCGACACCTACATCGACCTGCTGGAAACCCGGCGGACCTACTATGAGGGA CCTGGCGAGGGCAGCC

CCTTCGGCTGGAAGGACATCAAAGAATGGTACGAGATGCTGATGGGCCACTGCACCT ACTTCCCCGAGGAACT

GCGGAGCGTGAAGTACGCCTACAACGCCGACCTGTACAACGCCCTGAACGACCTGAA CAATCTCGTGATCACC

AGGGACGAGAACGAGAAGCTGGAATATTACGAGAAGTTCCAGATCATCGAGAACGTG TTCAAGCAGAAGAAGAA

GCCCACCCTGAAGCAGATCGCCAAAGAAATCCTCGTGAACGAAGAGGATATTAAGGG CTACAGAGTGACCAGCA CCGGCAAGCCCGAGTTCACCAACCTGAAGGTGTACCACGACATCAAGGACATTACCGCCC GGAAAGAGATTATT

GAGAACGCCGAGCTGCTGGATCAGATTGCCAAGATCCTGACCATCTACCAGAGCAGC GAGGACATCCAGGAAG

AACTGACCAATCTGAACTCCGAGCTGACCCAGGAAGAGATCGAGCAGATCTCTAATC TGAAGGGCTATACCGGC

ACCCACAACCTGAGCCTGAAGGCCATCAACCTGATCCTGGACGAGCTGTGGCACACC AACGACAACCAGATCG

CTATCTTCAACCGGCTGAAGCTGGTGCCCAAGAAGGTGGACCTGTCCCAGCAGAAAG AGATCCCCACCACCCT

GGTGGACGACTTCATCCTGAGCCCCGTCGTGAAGAGAAGCTTCATCCAGAGCATCAA AGTGATCAACGCCATCA

TCAAGAAGTACGGCCTGCCCAACGACATCATTATCGAGCTGGCCCGCGAGAAGAACT CCAAGGACGCCCAGAA

AATGATCAACGAGATGCAGAAGCGGAACCGGCAGACCAACGAGCGGATCGAGGAAAT CATCCGGACCACCGGC

AAAGAGAACGCCAAGTACCTGATCGAGAAGATCAAGCTGCACGACATGCAGGAAGGC AAGTGCCTGTACAGCC

TGGAAGCCATCCCTCTGGAAGATCTGCTGAACAACCCCTTCAACTATGAGGTGGACC ACATCATCCCCAGAAGC

GTGTCCTTCGACAACAGCTTCAACAACAAGGTGCTCGTGAAGCAGGAAGAAGCCAGC AAGAAGGGCAACCGGA

CCCCATTCCAGTACCTGAGCAGCAGCGACAGCAAGATCAGCTACGAAACCTTCAAGA AGCACATCCTGAATCTG

GCCAAGGGCAAGGGCAGAATCAGCAAGACCAAGAAAGAGTATCTGCTGGAAGAACGG GACATCAACAGGTTCT

CCGTGCAGAAAGACTTCATCAACCGGAACCTGGTGGATACCAGATACGCCACCAGAG GCCTGATGAACCTGCT

GCGGAGCTACTTCAGAGTGAACAACCTGGACGTGAAAGTGAAGTCCATCAATGGCGG CTTCACCAGCTTTCTGC

GGCGGAAGTGGAAGTTTAAGAAAGAGCGGAACAAGGGGTACAAGCACCACGCCGAGG ACGCCCTGATCATTGC

CAACGCCGATTTCATCTTCAAAGAGTGGAAGAAACTGGACAAGGCCAAAAAAGTGAT GGAAAACCAGATGTTCG

AGGAAAAGCAGGCCGAGAGCATGCCCGAGATCGAAACCGAGCAGGAGTACAAAGAGA TCTTCATCACCCCCCA

CCAGATCAAGCACATTAAGGACTTCAAGGACTACAAGTACAGCCACCGGGTGGACAA GAAGCCTAATAGAGAGC

TGATTAACGACACCCTGTACTCCACCCGGAAGGACGACAAGGGCAACACCCTGATCG TGAACAATCTGAACGGC

CTGTACGACAAGGACAATGACAAGCTGAAAAAGCTGATCAACAAGAGCCCCGAAAAG CTGCTGATGTACCACCA

CGACCCCCAGACCTACCAGAAACTGAAGCTGATTATGGAACAGTACGGCGACGAGAA GAATCCCCTGTACAAGT

ACTACGAGGAAACCGGGAACTACCTGACCAAGTACTCCAAAAAGGACAACGGCCCCG TGATCAAGAAGATTAAG

TATTACGGCAACAAACTGAACGCCCATCTGGACATCACCGACGACTACCCCAACAGC AGAAACAAGGTCGTGAA

GCTGTCCCTGAAGCCCTACAGATTCGACGTGTACCTGGACAATGGCGTGTACAAGTT CGTGACCGTGAAGAATC

TGGATGTGATCAAAAAAGAAAACTACTACGAAGTGAATAGCAAGTGCTATGAGGAAG CTAAGAAGCTGAAGAAGA

TCAGCAACCAGGCCGAGTTTATCGCCTCCTTCTACAACAACGATCTGATCAAGATCA ACGGCGAGCTGTATAGA

GTGATCGGCGTGAACAACGACCTGCTGAACCGGATCGAAGTGAACATGATCGACATC ACCTACCGCGAGTACCT

GGAAAACATGAACGACAAGAGGCCCCCCAGGATCATTAAGACAATCGCCTCCAAGAC CCAGAGCATTAAGAAGT

ACAGCACAGACATTCTGGGCAACCTGTATGAAGTGAAATCTAAGAAGCACCCTCAGA TCATCAAAAAGGGCAAAA

GGCCGGCGGCCACGAAAAAGGCCGGCCAGGCAAAAAAGAAAAAGGGATCCGGACGGG CTGACGCATTGGACG

ATTTTGATCTGGATATGCTGGGAAGTGACGCCCTCGATGATTTTGACCTTGACATGC TTGGTTCGGATGCCCTTG

ATGACTTTGACCTCGACATGCTCGGCAGTGACGCCCTTGATGATTTCGACCTGGACA TGCTGATTAACTGTACAG

GCAGTGGAGAGGGCAGAGGAAGTCTGCTAACATGCGGTGACGTCGAGGAGAATCCTG GCCCAATGGCCAAGC

CTTTGTCTCAAGAAGAATCCACCCTCATTGAAAGAGCAACGGCTACAATCAACAGCA TCCCCATCTCTGAAGACT

ACAGCGTCGCCAGCGCAGCTCTCTCTAGCGACGGCCGCATCTTCACTGGTGTCAATG TATATCATTTTACTGGG

GGACCTTGTGCAGAACTCGTGGTGCTGGGCACTGCTGCTGCTGCGGCAGCTGGCAAC CTGACTTGTATCGTCG

CGATCGGAAATGAGAACAGGGGCATCTTGAGCCCCTGCGGACGGTGCCGACAGGTGC TTCTCGATCTGCATCC

TGGGATCAAAGCCATAGTGAAGGACAGTGATGGACAGCCGACGGCAGTTGGGATTCG TGAATTGCTGCCCTCT

GGTTATGTGTGGGAGGGCTAAGAATTCCTAGAGCTCGCTGATCAGCCTCGACTGTGC CTTCTAGTTGCCAGCCA

TCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACT GTCCTTTCCTAATAAAAT

GAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTG GGGCAGGACAGCAAGG

GGGAGGATTGGGAAGAGAATAGCAGGCATGCTGGGGAGGTACCGAGGGCCTATTTCC CATGATTCCTTCATATT

TGCATATACGATACAAGGCTGTTAGAGAGATAATTGGAATTAATTTGACTGTAAACA CAAAGATATTAGTACAAAA

TACGTGACGTAGAAAGTAATAATTTCTTGGGTAGTTTGCAGTTTTAAAATTATGTTT TAAAATGGACTATCATATGC

TTACCGTAACTTGAAAGTATTTCGATTTCTTGGCTTTATATATCTTGTGGAAAGGAC GAAAcaccgCCTCAAGGATT

ACCGGGCTAGgTTTTAGTACTCTGGAAACAGAATCTACTAAAACAAGGCAAAATGCC GTGTTTATCTCGTCAACTT

GTTGGCGAGATTTTTGCGGCCGCAGGAACCCCTAGTGATGGAGTTGGCCACTCCCTC TCTGCGCGCTCGCTCG

CTCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGGGCTTTGCCCGGGCGGCC TCAGTGAGCGAGCG

AGCGCGCAGCTGCCTGCAGGGGCGCCTGATGCGGTATTTTCTCCTTACGCATCTGTG CGGTATTTCACACCGCA

TACGTCAAAGCAACCATAGTACGCGCCCTGTAGCGGCGCATTAAGCGCGGCGGGTGT GGTGGTTACGCGCAGC

GTGACCGCTACACTTGCCAGCGCCTTAGCGCCCGCTCCTTTCGCTTTCTTCCCTTCC TTTCTCGCCACGTTCGC

CGGCTTTCCCCGTCAAGCTCTAAATCGGGGGCTCCCTTTAGGGTTCCGATTTAGTGC TTTACGGCACCTCGACC CCAAAAAACTTGATTTGGGTGATGGTTCACGTAGTGGGCCATCGCCCTGATAGACGGTTT TTCGCCCTTTGACGT

TGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAACTGGAACAACACTCAACT CTATCTCGGGCTATTCTTT

TGATTTATAAGGGATTTTGCCGATTTCGGTCTATTGGTTAAAAAATGAGCTGATTTA ACAAAAATTTAACGCGAATT

TTAACAAAATATTAACGTTTACAATTTTATGGTGCACTCTCAGTACAATCTGCTCTG ATGCCGCATAGTTAAGCCA

GCCCCGACACCCGCCAACACCCGCTGACGCGCCCTGACGGGCTTGTCTGCTCCCGGC ATCCGCTTACAGACAA

GCTGTGACCGTCTCCGGGAGCTGCATGTGTCAGAGGTTTTCACCGTCATCACCGAAA CGCGCGAGACGAAAGG

GCCTCGTGATACGCCTATTTTTATAGGTTAATGTCATGATAATAATGGTTTCTTAGA CGTCAGGTGGCACTTTTCG

GGGAAATGTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTA TCCGCTCATGAGACAATAA

CCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTC CGTGTCGCCCTTATTCCCT

TTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAA AAGATGCTGAAGATCAGTT

GGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAG TTTTCGCCCCGAAGAAC

GTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTA TTGACGCCGGGCAAGAGC

AACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCA CAGAAAAGCATCTTACGG

ATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTG CGGCCAACTTACTTCTGA

CAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATG TAACTCGCCTTGATCGT

TGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCT GTAGCAATGGCAACAA

CGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAA TAGACTGGATGGAGGCG

GATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCT GATAAATCTGGAGCCGG

TGAGCGTGGAAGCCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCG TATCGTAGTTATCTACA

CGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTG CCTCACTGATTAAGCAT

TGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCAT TTTTAATTTAAAAGGATCTAG

GTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTC CACTGAGCGTCAGACCCC

GTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGC TTGCAAACAAAAAAACCAC

CGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGG TAACTGGCTTCAGCAGA

GCGCAGATACCAAATACTGTTCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAG AACTCTGTAGCACCGCCT

ACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCG TGTCTTACCGGGTTGGA

CTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTG CACACAGCCCAGCTTG

GAGCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCC ACGCTTCCCGAAGGGA

GAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGG AGCTTCCAGGGGGA

AACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGA TTTTTGTGATGCTCGTCA

GGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCC TTTTGCTGGCCTTTTG CTCACATGT pAAV-CMV-sadCas9-U6gRNA(Kcnq 2-sa sgRNA2) used in in vitro qPCR experiments (SEQ ID NO: 82)

CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCGTCGGGCGACC TTTGGTCGCCCGGCC

TCAGTGAGCGAGCGAGCGCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCC TGCGGCCTCTAGACTC

GAGGCGTTGACATTGATTATTGACTAGTTATTAATAGTAATCAATTACGGGGTCATT AGTTCATAGCCCATATATG

GAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGAC CCCCGCCCATTGACGT

CAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAAT GGGTGGAGTATTTACGGT

AAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTG ACGTCAATGACGGTAAAT

GGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGT ACATCTACGTATTAGTCA

TCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAATGGGCGTGGATAGCGGT TTGACTCACGGGGATTT

CCAAGTCTCCACCCCATTGACGTCAATGGGAGTTTGTTTTGGCACCAAAATCAACGG GACTTTCCAAAATGTCGT

AACAACTCCGCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTAT ATAAGCAGAGCTCTCT

GGCTAACTACCGGTGCCACCATGGCCCCAAAGAAGAAGCGGAAGGTCGGTATCCACG GAGTCCCAGCAGCCAA

GCGGAACTACATCCTGGGCCTGGCCATCGGCATCACCAGCGTGGGCTACGGCATCAT CGACTACGAGACACGG

GACGTGATCGATGCCGGCGTGCGGCTGTTCAAAGAGGCCAACGTGGAAAACAACGAG GGCAGGCGGAGCAAG

AGAGGCGCCAGAAGGCTGAAGCGGCGGAGGCGGCATAGAATCCAGAGAGTGAAGAAG CTGCTGTTCGACTAC

AACCTGCTGACCGACCACAGCGAGCTGAGCGGCATCAACCCCTACGAGGCCAGAGTG AAGGGCCTGAGCCAG

AAGCTGAGCGAGGAAGAGTTCTCTGCCGCCCTGCTGCACCTGGCCAAGAGAAGAGGC GTGCACAACGTGAACG

AGGTGGAAGAGGACACCGGCAACGAGCTGTCCACCAAAGAGCAGATCAGCCGGAACA GCAAGGCCCTGGAAG

AGAAATACGTGGCCGAACTGCAGCTGGAACGGCTGAAGAAAGACGGCGAAGTGCGGG GCAGCATCAACAGATT

CAAGACCAGCGACTACGTGAAAGAAGCCAAACAGCTGCTGAAGGTGCAGAAGGCCTA CCACCAGCTGGACCAG AGCTTCATCGACACCTACATCGACCTGCTGGAAACCCGGCGGACCTACTATGAGGGACCT GGCGAGGGCAGCC

CCTTCGGCTGGAAGGACATCAAAGAATGGTACGAGATGCTGATGGGCCACTGCACCT ACTTCCCCGAGGAACT

GCGGAGCGTGAAGTACGCCTACAACGCCGACCTGTACAACGCCCTGAACGACCTGAA CAATCTCGTGATCACC

AGGGACGAGAACGAGAAGCTGGAATATTACGAGAAGTTCCAGATCATCGAGAACGTG TTCAAGCAGAAGAAGAA

GCCCACCCTGAAGCAGATCGCCAAAGAAATCCTCGTGAACGAAGAGGATATTAAGGG CTACAGAGTGACCAGCA

CCGGCAAGCCCGAGTTCACCAACCTGAAGGTGTACCACGACATCAAGGACATTACCG CCCGGAAAGAGATTATT

GAGAACGCCGAGCTGCTGGATCAGATTGCCAAGATCCTGACCATCTACCAGAGCAGC GAGGACATCCAGGAAG

AACTGACCAATCTGAACTCCGAGCTGACCCAGGAAGAGATCGAGCAGATCTCTAATC TGAAGGGCTATACCGGC

ACCCACAACCTGAGCCTGAAGGCCATCAACCTGATCCTGGACGAGCTGTGGCACACC AACGACAACCAGATCG

CTATCTTCAACCGGCTGAAGCTGGTGCCCAAGAAGGTGGACCTGTCCCAGCAGAAAG AGATCCCCACCACCCT

GGTGGACGACTTCATCCTGAGCCCCGTCGTGAAGAGAAGCTTCATCCAGAGCATCAA AGTGATCAACGCCATCA

TCAAGAAGTACGGCCTGCCCAACGACATCATTATCGAGCTGGCCCGCGAGAAGAACT CCAAGGACGCCCAGAA

AATGATCAACGAGATGCAGAAGCGGAACCGGCAGACCAACGAGCGGATCGAGGAAAT CATCCGGACCACCGGC

AAAGAGAACGCCAAGTACCTGATCGAGAAGATCAAGCTGCACGACATGCAGGAAGGC AAGTGCCTGTACAGCC

TGGAAGCCATCCCTCTGGAAGATCTGCTGAACAACCCCTTCAACTATGAGGTGGACC ACATCATCCCCAGAAGC

GTGTCCTTCGACAACAGCTTCAACAACAAGGTGCTCGTGAAGCAGGAAGAAGCCAGC AAGAAGGGCAACCGGA

CCCCATTCCAGTACCTGAGCAGCAGCGACAGCAAGATCAGCTACGAAACCTTCAAGA AGCACATCCTGAATCTG

GCCAAGGGCAAGGGCAGAATCAGCAAGACCAAGAAAGAGTATCTGCTGGAAGAACGG GACATCAACAGGTTCT

CCGTGCAGAAAGACTTCATCAACCGGAACCTGGTGGATACCAGATACGCCACCAGAG GCCTGATGAACCTGCT

GCGGAGCTACTTCAGAGTGAACAACCTGGACGTGAAAGTGAAGTCCATCAATGGCGG CTTCACCAGCTTTCTGC

GGCGGAAGTGGAAGTTTAAGAAAGAGCGGAACAAGGGGTACAAGCACCACGCCGAGG ACGCCCTGATCATTGC

CAACGCCGATTTCATCTTCAAAGAGTGGAAGAAACTGGACAAGGCCAAAAAAGTGAT GGAAAACCAGATGTTCG

AGGAAAAGCAGGCCGAGAGCATGCCCGAGATCGAAACCGAGCAGGAGTACAAAGAGA TCTTCATCACCCCCCA

CCAGATCAAGCACATTAAGGACTTCAAGGACTACAAGTACAGCCACCGGGTGGACAA GAAGCCTAATAGAGAGC

TGATTAACGACACCCTGTACTCCACCCGGAAGGACGACAAGGGCAACACCCTGATCG TGAACAATCTGAACGGC

CTGTACGACAAGGACAATGACAAGCTGAAAAAGCTGATCAACAAGAGCCCCGAAAAG CTGCTGATGTACCACCA

CGACCCCCAGACCTACCAGAAACTGAAGCTGATTATGGAACAGTACGGCGACGAGAA GAATCCCCTGTACAAGT

ACTACGAGGAAACCGGGAACTACCTGACCAAGTACTCCAAAAAGGACAACGGCCCCG TGATCAAGAAGATTAAG

TATTACGGCAACAAACTGAACGCCCATCTGGACATCACCGACGACTACCCCAACAGC AGAAACAAGGTCGTGAA

GCTGTCCCTGAAGCCCTACAGATTCGACGTGTACCTGGACAATGGCGTGTACAAGTT CGTGACCGTGAAGAATC

TGGATGTGATCAAAAAAGAAAACTACTACGAAGTGAATAGCAAGTGCTATGAGGAAG CTAAGAAGCTGAAGAAGA

TCAGCAACCAGGCCGAGTTTATCGCCTCCTTCTACAACAACGATCTGATCAAGATCA ACGGCGAGCTGTATAGA

GTGATCGGCGTGAACAACGACCTGCTGAACCGGATCGAAGTGAACATGATCGACATC ACCTACCGCGAGTACCT

GGAAAACATGAACGACAAGAGGCCCCCCAGGATCATTAAGACAATCGCCTCCAAGAC CCAGAGCATTAAGAAGT

ACAGCACAGACATTCTGGGCAACCTGTATGAAGTGAAATCTAAGAAGCACCCTCAGA TCATCAAAAAGGGCAAAA

GGCCGGCGGCCACGAAAAAGGCCGGCCAGGCAAAAAAGAAAAAGGGATCCGGACGGG CTGACGCATTGGACG

ATTTTGATCTGGATATGCTGGGAAGTGACGCCCTCGATGATTTTGACCTTGACATGC TTGGTTCGGATGCCCTTG

ATGACTTTGACCTCGACATGCTCGGCAGTGACGCCCTTGATGATTTCGACCTGGACA TGCTGATTAACTGTACAG

GCAGTGGAGAGGGCAGAGGAAGTCTGCTAACATGCGGTGACGTCGAGGAGAATCCTG GCCCAATGGCCAAGC

CTTTGTCTCAAGAAGAATCCACCCTCATTGAAAGAGCAACGGCTACAATCAACAGCA TCCCCATCTCTGAAGACT

ACAGCGTCGCCAGCGCAGCTCTCTCTAGCGACGGCCGCATCTTCACTGGTGTCAATG TATATCATTTTACTGGG

GGACCTTGTGCAGAACTCGTGGTGCTGGGCACTGCTGCTGCTGCGGCAGCTGGCAAC CTGACTTGTATCGTCG

CGATCGGAAATGAGAACAGGGGCATCTTGAGCCCCTGCGGACGGTGCCGACAGGTGC TTCTCGATCTGCATCC

TGGGATCAAAGCCATAGTGAAGGACAGTGATGGACAGCCGACGGCAGTTGGGATTCG TGAATTGCTGCCCTCT

GGTTATGTGTGGGAGGGCTAAGAATTCCTAGAGCTCGCTGATCAGCCTCGACTGTGC CTTCTAGTTGCCAGCCA

TCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACT GTCCTTTCCTAATAAAAT

GAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTG GGGCAGGACAGCAAGG

GGGAGGATTGGGAAGAGAATAGCAGGCATGCTGGGGAGGTACCGAGGGCCTATTTCC CATGATTCCTTCATATT

TGCATATACGATACAAGGCTGTTAGAGAGATAATTGGAATTAATTTGACTGTAAACA CAAAGATATTAGTACAAAA

TACGTGACGTAGAAAGTAATAATTTCTTGGGTAGTTTGCAGTTTTAAAATTATGTTT TAAAATGGACTATCATATGC

TTACCGTAACTTGAAAGTATTTCGATTTCTTGGCTTTATATATCTTGTGGAAAGGAC GAAAcaccgCTAGCCCGGTA

ATCCTTGAGGgTTTTAGTACTCTGGAAACAGAATCTACTAAAACAAGGCAAAATGCC GTGTTTATCTCGTCAACTT

GTTGGCGAGATTTTTGCGGCCGCAGGAACCCCTAGTGATGGAGTTGGCCACTCCCTC TCTGCGCGCTCGCTCG CTCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGGGCTTTGCCCGGGCGGCCTCA GTGAGCGAGCG

AGCGCGCAGCTGCCTGCAGGGGCGCCTGATGCGGTATTTTCTCCTTACGCATCTGTG CGGTATTTCACACCGCA

TACGTCAAAGCAACCATAGTACGCGCCCTGTAGCGGCGCATTAAGCGCGGCGGGTGT GGTGGTTACGCGCAGC

GTGACCGCTACACTTGCCAGCGCCTTAGCGCCCGCTCCTTTCGCTTTCTTCCCTTCC TTTCTCGCCACGTTCGC

CGGCTTTCCCCGTCAAGCTCTAAATCGGGGGCTCCCTTTAGGGTTCCGATTTAGTGC TTTACGGCACCTCGACC

CCAAAAAACTTGATTTGGGTGATGGTTCACGTAGTGGGCCATCGCCCTGATAGACGG TTTTTCGCCCTTTGACGT

TGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAACTGGAACAACACTCAACT CTATCTCGGGCTATTCTTT

TGATTTATAAGGGATTTTGCCGATTTCGGTCTATTGGTTAAAAAATGAGCTGATTTA ACAAAAATTTAACGCGAATT

TTAACAAAATATTAACGTTTACAATTTTATGGTGCACTCTCAGTACAATCTGCTCTG ATGCCGCATAGTTAAGCCA

GCCCCGACACCCGCCAACACCCGCTGACGCGCCCTGACGGGCTTGTCTGCTCCCGGC ATCCGCTTACAGACAA

GCTGTGACCGTCTCCGGGAGCTGCATGTGTCAGAGGTTTTCACCGTCATCACCGAAA CGCGCGAGACGAAAGG

GCCTCGTGATACGCCTATTTTTATAGGTTAATGTCATGATAATAATGGTTTCTTAGA CGTCAGGTGGCACTTTTCG

GGGAAATGTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTA TCCGCTCATGAGACAATAA

CCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTC CGTGTCGCCCTTATTCCCT

TTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAA AAGATGCTGAAGATCAGTT

GGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAG TTTTCGCCCCGAAGAAC

GTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTA TTGACGCCGGGCAAGAGC

AACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCA CAGAAAAGCATCTTACGG

ATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTG CGGCCAACTTACTTCTGA

CAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATG TAACTCGCCTTGATCGT

TGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCT GTAGCAATGGCAACAA

CGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAA TAGACTGGATGGAGGCG

GATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCT GATAAATCTGGAGCCGG

TGAGCGTGGAAGCCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCG TATCGTAGTTATCTACA

CGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTG CCTCACTGATTAAGCAT

TGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCAT TTTTAATTTAAAAGGATCTAG

GTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTC CACTGAGCGTCAGACCCC

GTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGC TTGCAAACAAAAAAACCAC

CGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGG TAACTGGCTTCAGCAGA

GCGCAGATACCAAATACTGTTCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAG AACTCTGTAGCACCGCCT

ACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCG TGTCTTACCGGGTTGGA

CTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTG CACACAGCCCAGCTTG

GAGCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCC ACGCTTCCCGAAGGGA

GAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGG AGCTTCCAGGGGGA

AACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGA TTTTTGTGATGCTCGTCA

GGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCC TTTTGCTGGCCTTTTG CTCACATGT pAAV-CMV-sadCas9-U6gRNA(Kcnq 2-sa sgRNA3) used in in vitro qPCR experiments (SEQ ID NO: 83)

CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCGTCGGGCGACC TTTGGTCGCCCGGCC

TCAGTGAGCGAGCGAGCGCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCC TGCGGCCTCTAGACTC

GAGGCGTTGACATTGATTATTGACTAGTTATTAATAGTAATCAATTACGGGGTCATT AGTTCATAGCCCATATATG

GAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGAC CCCCGCCCATTGACGT

CAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAAT GGGTGGAGTATTTACGGT

AAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTG ACGTCAATGACGGTAAAT

GGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGT ACATCTACGTATTAGTCA

TCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAATGGGCGTGGATAGCGGT TTGACTCACGGGGATTT

CCAAGTCTCCACCCCATTGACGTCAATGGGAGTTTGTTTTGGCACCAAAATCAACGG GACTTTCCAAAATGTCGT

AACAACTCCGCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTAT ATAAGCAGAGCTCTCT

GGCTAACTACCGGTGCCACCATGGCCCCAAAGAAGAAGCGGAAGGTCGGTATCCACG GAGTCCCAGCAGCCAA

GCGGAACTACATCCTGGGCCTGGCCATCGGCATCACCAGCGTGGGCTACGGCATCAT CGACTACGAGACACGG

GACGTGATCGATGCCGGCGTGCGGCTGTTCAAAGAGGCCAACGTGGAAAACAACGAG GGCAGGCGGAGCAAG

AGAGGCGCCAGAAGGCTGAAGCGGCGGAGGCGGCATAGAATCCAGAGAGTGAAGAAG CTGCTGTTCGACTAC AACCTGCTGACCGACCACAGCGAGCTGAGCGGCATCAACCCCTACGAGGCCAGAGTGAAG GGCCTGAGCCAG

AAGCTGAGCGAGGAAGAGTTCTCTGCCGCCCTGCTGCACCTGGCCAAGAGAAGAGGC GTGCACAACGTGAACG

AGGTGGAAGAGGACACCGGCAACGAGCTGTCCACCAAAGAGCAGATCAGCCGGAACA GCAAGGCCCTGGAAG

AGAAATACGTGGCCGAACTGCAGCTGGAACGGCTGAAGAAAGACGGCGAAGTGCGGG GCAGCATCAACAGATT

CAAGACCAGCGACTACGTGAAAGAAGCCAAACAGCTGCTGAAGGTGCAGAAGGCCTA CCACCAGCTGGACCAG

AGCTTCATCGACACCTACATCGACCTGCTGGAAACCCGGCGGACCTACTATGAGGGA CCTGGCGAGGGCAGCC

CCTTCGGCTGGAAGGACATCAAAGAATGGTACGAGATGCTGATGGGCCACTGCACCT ACTTCCCCGAGGAACT

GCGGAGCGTGAAGTACGCCTACAACGCCGACCTGTACAACGCCCTGAACGACCTGAA CAATCTCGTGATCACC

AGGGACGAGAACGAGAAGCTGGAATATTACGAGAAGTTCCAGATCATCGAGAACGTG TTCAAGCAGAAGAAGAA

GCCCACCCTGAAGCAGATCGCCAAAGAAATCCTCGTGAACGAAGAGGATATTAAGGG CTACAGAGTGACCAGCA

CCGGCAAGCCCGAGTTCACCAACCTGAAGGTGTACCACGACATCAAGGACATTACCG CCCGGAAAGAGATTATT

GAGAACGCCGAGCTGCTGGATCAGATTGCCAAGATCCTGACCATCTACCAGAGCAGC GAGGACATCCAGGAAG

AACTGACCAATCTGAACTCCGAGCTGACCCAGGAAGAGATCGAGCAGATCTCTAATC TGAAGGGCTATACCGGC

ACCCACAACCTGAGCCTGAAGGCCATCAACCTGATCCTGGACGAGCTGTGGCACACC AACGACAACCAGATCG

CTATCTTCAACCGGCTGAAGCTGGTGCCCAAGAAGGTGGACCTGTCCCAGCAGAAAG AGATCCCCACCACCCT

GGTGGACGACTTCATCCTGAGCCCCGTCGTGAAGAGAAGCTTCATCCAGAGCATCAA AGTGATCAACGCCATCA

TCAAGAAGTACGGCCTGCCCAACGACATCATTATCGAGCTGGCCCGCGAGAAGAACT CCAAGGACGCCCAGAA

AATGATCAACGAGATGCAGAAGCGGAACCGGCAGACCAACGAGCGGATCGAGGAAAT CATCCGGACCACCGGC

AAAGAGAACGCCAAGTACCTGATCGAGAAGATCAAGCTGCACGACATGCAGGAAGGC AAGTGCCTGTACAGCC

TGGAAGCCATCCCTCTGGAAGATCTGCTGAACAACCCCTTCAACTATGAGGTGGACC ACATCATCCCCAGAAGC

GTGTCCTTCGACAACAGCTTCAACAACAAGGTGCTCGTGAAGCAGGAAGAAGCCAGC AAGAAGGGCAACCGGA

CCCCATTCCAGTACCTGAGCAGCAGCGACAGCAAGATCAGCTACGAAACCTTCAAGA AGCACATCCTGAATCTG

GCCAAGGGCAAGGGCAGAATCAGCAAGACCAAGAAAGAGTATCTGCTGGAAGAACGG GACATCAACAGGTTCT

CCGTGCAGAAAGACTTCATCAACCGGAACCTGGTGGATACCAGATACGCCACCAGAG GCCTGATGAACCTGCT

GCGGAGCTACTTCAGAGTGAACAACCTGGACGTGAAAGTGAAGTCCATCAATGGCGG CTTCACCAGCTTTCTGC

GGCGGAAGTGGAAGTTTAAGAAAGAGCGGAACAAGGGGTACAAGCACCACGCCGAGG ACGCCCTGATCATTGC

CAACGCCGATTTCATCTTCAAAGAGTGGAAGAAACTGGACAAGGCCAAAAAAGTGAT GGAAAACCAGATGTTCG

AGGAAAAGCAGGCCGAGAGCATGCCCGAGATCGAAACCGAGCAGGAGTACAAAGAGA TCTTCATCACCCCCCA

CCAGATCAAGCACATTAAGGACTTCAAGGACTACAAGTACAGCCACCGGGTGGACAA GAAGCCTAATAGAGAGC

TGATTAACGACACCCTGTACTCCACCCGGAAGGACGACAAGGGCAACACCCTGATCG TGAACAATCTGAACGGC

CTGTACGACAAGGACAATGACAAGCTGAAAAAGCTGATCAACAAGAGCCCCGAAAAG CTGCTGATGTACCACCA

CGACCCCCAGACCTACCAGAAACTGAAGCTGATTATGGAACAGTACGGCGACGAGAA GAATCCCCTGTACAAGT

ACTACGAGGAAACCGGGAACTACCTGACCAAGTACTCCAAAAAGGACAACGGCCCCG TGATCAAGAAGATTAAG

TATTACGGCAACAAACTGAACGCCCATCTGGACATCACCGACGACTACCCCAACAGC AGAAACAAGGTCGTGAA

GCTGTCCCTGAAGCCCTACAGATTCGACGTGTACCTGGACAATGGCGTGTACAAGTT CGTGACCGTGAAGAATC

TGGATGTGATCAAAAAAGAAAACTACTACGAAGTGAATAGCAAGTGCTATGAGGAAG CTAAGAAGCTGAAGAAGA

TCAGCAACCAGGCCGAGTTTATCGCCTCCTTCTACAACAACGATCTGATCAAGATCA ACGGCGAGCTGTATAGA

GTGATCGGCGTGAACAACGACCTGCTGAACCGGATCGAAGTGAACATGATCGACATC ACCTACCGCGAGTACCT

GGAAAACATGAACGACAAGAGGCCCCCCAGGATCATTAAGACAATCGCCTCCAAGAC CCAGAGCATTAAGAAGT

ACAGCACAGACATTCTGGGCAACCTGTATGAAGTGAAATCTAAGAAGCACCCTCAGA TCATCAAAAAGGGCAAAA

GGCCGGCGGCCACGAAAAAGGCCGGCCAGGCAAAAAAGAAAAAGGGATCCGGACGGG CTGACGCATTGGACG

ATTTTGATCTGGATATGCTGGGAAGTGACGCCCTCGATGATTTTGACCTTGACATGC TTGGTTCGGATGCCCTTG

ATGACTTTGACCTCGACATGCTCGGCAGTGACGCCCTTGATGATTTCGACCTGGACA TGCTGATTAACTGTACAG

GCAGTGGAGAGGGCAGAGGAAGTCTGCTAACATGCGGTGACGTCGAGGAGAATCCTG GCCCAATGGCCAAGC

CTTTGTCTCAAGAAGAATCCACCCTCATTGAAAGAGCAACGGCTACAATCAACAGCA TCCCCATCTCTGAAGACT

ACAGCGTCGCCAGCGCAGCTCTCTCTAGCGACGGCCGCATCTTCACTGGTGTCAATG TATATCATTTTACTGGG

GGACCTTGTGCAGAACTCGTGGTGCTGGGCACTGCTGCTGCTGCGGCAGCTGGCAAC CTGACTTGTATCGTCG

CGATCGGAAATGAGAACAGGGGCATCTTGAGCCCCTGCGGACGGTGCCGACAGGTGC TTCTCGATCTGCATCC

TGGGATCAAAGCCATAGTGAAGGACAGTGATGGACAGCCGACGGCAGTTGGGATTCG TGAATTGCTGCCCTCT

GGTTATGTGTGGGAGGGCTAAGAATTCCTAGAGCTCGCTGATCAGCCTCGACTGTGC CTTCTAGTTGCCAGCCA

TCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACT GTCCTTTCCTAATAAAAT

GAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTG GGGCAGGACAGCAAGG

GGGAGGATTGGGAAGAGAATAGCAGGCATGCTGGGGAGGTACCGAGGGCCTATTTCC CATGATTCCTTCATATT TGCATATACGATACAAGGCTGTTAGAGAGATAATTGGAATTAATTTGACTGTAAACACAA AGATATTAGTACAAAA

TACGTGACGTAGAAAGTAATAATTTCTTGGGTAGTTTGCAGTTTTAAAATTATGTTT TAAAATGGACTATCATATGC

TTACCGTAACTTGAAAGTATTTCGATTTCTTGGCTTTATATATCTTGTGGAAAGGAC GAAAcaccgGCAGGGCTGGA

CTCCCCCTCgTTTTAGTACTCTGGAAACAGAATCTACTAAAACAAGGCAAAATGCCG TGTTTATCTCGTCAACTTG

TTGGCGAGATTTTTGCGGCCGCAGGAACCCCTAGTGATGGAGTTGGCCACTCCCTCT CTGCGCGCTCGCTCGC

TCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGGGCTTTGCCCGGGCGGCCT CAGTGAGCGAGCGA

GCGCGCAGCTGCCTGCAGGGGCGCCTGATGCGGTATTTTCTCCTTACGCATCTGTGC GGTATTTCACACCGCAT

ACGTCAAAGCAACCATAGTACGCGCCCTGTAGCGGCGCATTAAGCGCGGCGGGTGTG GTGGTTACGCGCAGC

GTGACCGCTACACTTGCCAGCGCCTTAGCGCCCGCTCCTTTCGCTTTCTTCCCTTCC TTTCTCGCCACGTTCGC

CGGCTTTCCCCGTCAAGCTCTAAATCGGGGGCTCCCTTTAGGGTTCCGATTTAGTGC TTTACGGCACCTCGACC

CCAAAAAACTTGATTTGGGTGATGGTTCACGTAGTGGGCCATCGCCCTGATAGACGG TTTTTCGCCCTTTGACGT

TGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAACTGGAACAACACTCAACT CTATCTCGGGCTATTCTTT

TGATTTATAAGGGATTTTGCCGATTTCGGTCTATTGGTTAAAAAATGAGCTGATTTA ACAAAAATTTAACGCGAATT

TTAACAAAATATTAACGTTTACAATTTTATGGTGCACTCTCAGTACAATCTGCTCTG ATGCCGCATAGTTAAGCCA

GCCCCGACACCCGCCAACACCCGCTGACGCGCCCTGACGGGCTTGTCTGCTCCCGGC ATCCGCTTACAGACAA

GCTGTGACCGTCTCCGGGAGCTGCATGTGTCAGAGGTTTTCACCGTCATCACCGAAA CGCGCGAGACGAAAGG

GCCTCGTGATACGCCTATTTTTATAGGTTAATGTCATGATAATAATGGTTTCTTAGA CGTCAGGTGGCACTTTTCG

GGGAAATGTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTA TCCGCTCATGAGACAATAA

CCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTC CGTGTCGCCCTTATTCCCT

TTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAA AAGATGCTGAAGATCAGTT

GGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAG TTTTCGCCCCGAAGAAC

GTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTA TTGACGCCGGGCAAGAGC

AACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCA CAGAAAAGCATCTTACGG

ATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTG CGGCCAACTTACTTCTGA

CAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATG TAACTCGCCTTGATCGT

TGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCT GTAGCAATGGCAACAA

CGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAA TAGACTGGATGGAGGCG

GATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCT GATAAATCTGGAGCCGG

TGAGCGTGGAAGCCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCG TATCGTAGTTATCTACA

CGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTG CCTCACTGATTAAGCAT

TGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCAT TTTTAATTTAAAAGGATCTAG

GTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTC CACTGAGCGTCAGACCCC

GTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGC TTGCAAACAAAAAAACCAC

CGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGG TAACTGGCTTCAGCAGA

GCGCAGATACCAAATACTGTTCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAG AACTCTGTAGCACCGCCT

ACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCG TGTCTTACCGGGTTGGA

CTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTG CACACAGCCCAGCTTG

GAGCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCC ACGCTTCCCGAAGGGA

GAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGG AGCTTCCAGGGGGA

AACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGA TTTTTGTGATGCTCGTCA

GGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCC TTTTGCTGGCCTTTTG CTCACATGT pAAV-CMV-sadCas9-U6gRNA(Kcnq 2-sa sgRNA4) used in in vitro qPCR experiments (SEQ ID NO: 84)

CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCGTCGGGCGACC TTTGGTCGCCCGGCC

TCAGTGAGCGAGCGAGCGCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCC TGCGGCCTCTAGACTC

GAGGCGTTGACATTGATTATTGACTAGTTATTAATAGTAATCAATTACGGGGTCATT AGTTCATAGCCCATATATG

GAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGAC CCCCGCCCATTGACGT

CAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAAT GGGTGGAGTATTTACGGT

AAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTG ACGTCAATGACGGTAAAT

GGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGT ACATCTACGTATTAGTCA

TCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAATGGGCGTGGATAGCGGT TTGACTCACGGGGATTT

CCAAGTCTCCACCCCATTGACGTCAATGGGAGTTTGTTTTGGCACCAAAATCAACGG GACTTTCCAAAATGTCGT AACAACTCCGCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTATATA AGCAGAGCTCTCT

GGCTAACTACCGGTGCCACCATGGCCCCAAAGAAGAAGCGGAAGGTCGGTATCCACG GAGTCCCAGCAGCCAA

GCGGAACTACATCCTGGGCCTGGCCATCGGCATCACCAGCGTGGGCTACGGCATCAT CGACTACGAGACACGG

GACGTGATCGATGCCGGCGTGCGGCTGTTCAAAGAGGCCAACGTGGAAAACAACGAG GGCAGGCGGAGCAAG

AGAGGCGCCAGAAGGCTGAAGCGGCGGAGGCGGCATAGAATCCAGAGAGTGAAGAAG CTGCTGTTCGACTAC

AACCTGCTGACCGACCACAGCGAGCTGAGCGGCATCAACCCCTACGAGGCCAGAGTG AAGGGCCTGAGCCAG

AAGCTGAGCGAGGAAGAGTTCTCTGCCGCCCTGCTGCACCTGGCCAAGAGAAGAGGC GTGCACAACGTGAACG

AGGTGGAAGAGGACACCGGCAACGAGCTGTCCACCAAAGAGCAGATCAGCCGGAACA GCAAGGCCCTGGAAG

AGAAATACGTGGCCGAACTGCAGCTGGAACGGCTGAAGAAAGACGGCGAAGTGCGGG GCAGCATCAACAGATT

CAAGACCAGCGACTACGTGAAAGAAGCCAAACAGCTGCTGAAGGTGCAGAAGGCCTA CCACCAGCTGGACCAG

AGCTTCATCGACACCTACATCGACCTGCTGGAAACCCGGCGGACCTACTATGAGGGA CCTGGCGAGGGCAGCC

CCTTCGGCTGGAAGGACATCAAAGAATGGTACGAGATGCTGATGGGCCACTGCACCT ACTTCCCCGAGGAACT

GCGGAGCGTGAAGTACGCCTACAACGCCGACCTGTACAACGCCCTGAACGACCTGAA CAATCTCGTGATCACC

AGGGACGAGAACGAGAAGCTGGAATATTACGAGAAGTTCCAGATCATCGAGAACGTG TTCAAGCAGAAGAAGAA

GCCCACCCTGAAGCAGATCGCCAAAGAAATCCTCGTGAACGAAGAGGATATTAAGGG CTACAGAGTGACCAGCA

CCGGCAAGCCCGAGTTCACCAACCTGAAGGTGTACCACGACATCAAGGACATTACCG CCCGGAAAGAGATTATT

GAGAACGCCGAGCTGCTGGATCAGATTGCCAAGATCCTGACCATCTACCAGAGCAGC GAGGACATCCAGGAAG

AACTGACCAATCTGAACTCCGAGCTGACCCAGGAAGAGATCGAGCAGATCTCTAATC TGAAGGGCTATACCGGC

ACCCACAACCTGAGCCTGAAGGCCATCAACCTGATCCTGGACGAGCTGTGGCACACC AACGACAACCAGATCG

CTATCTTCAACCGGCTGAAGCTGGTGCCCAAGAAGGTGGACCTGTCCCAGCAGAAAG AGATCCCCACCACCCT

GGTGGACGACTTCATCCTGAGCCCCGTCGTGAAGAGAAGCTTCATCCAGAGCATCAA AGTGATCAACGCCATCA

TCAAGAAGTACGGCCTGCCCAACGACATCATTATCGAGCTGGCCCGCGAGAAGAACT CCAAGGACGCCCAGAA

AATGATCAACGAGATGCAGAAGCGGAACCGGCAGACCAACGAGCGGATCGAGGAAAT CATCCGGACCACCGGC

AAAGAGAACGCCAAGTACCTGATCGAGAAGATCAAGCTGCACGACATGCAGGAAGGC AAGTGCCTGTACAGCC

TGGAAGCCATCCCTCTGGAAGATCTGCTGAACAACCCCTTCAACTATGAGGTGGACC ACATCATCCCCAGAAGC

GTGTCCTTCGACAACAGCTTCAACAACAAGGTGCTCGTGAAGCAGGAAGAAGCCAGC AAGAAGGGCAACCGGA

CCCCATTCCAGTACCTGAGCAGCAGCGACAGCAAGATCAGCTACGAAACCTTCAAGA AGCACATCCTGAATCTG

GCCAAGGGCAAGGGCAGAATCAGCAAGACCAAGAAAGAGTATCTGCTGGAAGAACGG GACATCAACAGGTTCT

CCGTGCAGAAAGACTTCATCAACCGGAACCTGGTGGATACCAGATACGCCACCAGAG GCCTGATGAACCTGCT

GCGGAGCTACTTCAGAGTGAACAACCTGGACGTGAAAGTGAAGTCCATCAATGGCGG CTTCACCAGCTTTCTGC

GGCGGAAGTGGAAGTTTAAGAAAGAGCGGAACAAGGGGTACAAGCACCACGCCGAGG ACGCCCTGATCATTGC

CAACGCCGATTTCATCTTCAAAGAGTGGAAGAAACTGGACAAGGCCAAAAAAGTGAT GGAAAACCAGATGTTCG

AGGAAAAGCAGGCCGAGAGCATGCCCGAGATCGAAACCGAGCAGGAGTACAAAGAGA TCTTCATCACCCCCCA

CCAGATCAAGCACATTAAGGACTTCAAGGACTACAAGTACAGCCACCGGGTGGACAA GAAGCCTAATAGAGAGC

TGATTAACGACACCCTGTACTCCACCCGGAAGGACGACAAGGGCAACACCCTGATCG TGAACAATCTGAACGGC

CTGTACGACAAGGACAATGACAAGCTGAAAAAGCTGATCAACAAGAGCCCCGAAAAG CTGCTGATGTACCACCA

CGACCCCCAGACCTACCAGAAACTGAAGCTGATTATGGAACAGTACGGCGACGAGAA GAATCCCCTGTACAAGT

ACTACGAGGAAACCGGGAACTACCTGACCAAGTACTCCAAAAAGGACAACGGCCCCG TGATCAAGAAGATTAAG

TATTACGGCAACAAACTGAACGCCCATCTGGACATCACCGACGACTACCCCAACAGC AGAAACAAGGTCGTGAA

GCTGTCCCTGAAGCCCTACAGATTCGACGTGTACCTGGACAATGGCGTGTACAAGTT CGTGACCGTGAAGAATC

TGGATGTGATCAAAAAAGAAAACTACTACGAAGTGAATAGCAAGTGCTATGAGGAAG CTAAGAAGCTGAAGAAGA

TCAGCAACCAGGCCGAGTTTATCGCCTCCTTCTACAACAACGATCTGATCAAGATCA ACGGCGAGCTGTATAGA

GTGATCGGCGTGAACAACGACCTGCTGAACCGGATCGAAGTGAACATGATCGACATC ACCTACCGCGAGTACCT

GGAAAACATGAACGACAAGAGGCCCCCCAGGATCATTAAGACAATCGCCTCCAAGAC CCAGAGCATTAAGAAGT

ACAGCACAGACATTCTGGGCAACCTGTATGAAGTGAAATCTAAGAAGCACCCTCAGA TCATCAAAAAGGGCAAAA

GGCCGGCGGCCACGAAAAAGGCCGGCCAGGCAAAAAAGAAAAAGGGATCCGGACGGG CTGACGCATTGGACG

ATTTTGATCTGGATATGCTGGGAAGTGACGCCCTCGATGATTTTGACCTTGACATGC TTGGTTCGGATGCCCTTG

ATGACTTTGACCTCGACATGCTCGGCAGTGACGCCCTTGATGATTTCGACCTGGACA TGCTGATTAACTGTACAG

GCAGTGGAGAGGGCAGAGGAAGTCTGCTAACATGCGGTGACGTCGAGGAGAATCCTG GCCCAATGGCCAAGC

CTTTGTCTCAAGAAGAATCCACCCTCATTGAAAGAGCAACGGCTACAATCAACAGCA TCCCCATCTCTGAAGACT

ACAGCGTCGCCAGCGCAGCTCTCTCTAGCGACGGCCGCATCTTCACTGGTGTCAATG TATATCATTTTACTGGG

GGACCTTGTGCAGAACTCGTGGTGCTGGGCACTGCTGCTGCTGCGGCAGCTGGCAAC CTGACTTGTATCGTCG

CGATCGGAAATGAGAACAGGGGCATCTTGAGCCCCTGCGGACGGTGCCGACAGGTGC TTCTCGATCTGCATCC TGGGATCAAAGCCATAGTGAAGGACAGTGATGGACAGCCGACGGCAGTTGGGATTCGTGA ATTGCTGCCCTCT

GGTTATGTGTGGGAGGGCTAAGAATTCCTAGAGCTCGCTGATCAGCCTCGACTGTGC CTTCTAGTTGCCAGCCA

TCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACT GTCCTTTCCTAATAAAAT

GAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTG GGGCAGGACAGCAAGG

GGGAGGATTGGGAAGAGAATAGCAGGCATGCTGGGGAGGTACCGAGGGCCTATTTCC CATGATTCCTTCATATT

TGCATATACGATACAAGGCTGTTAGAGAGATAATTGGAATTAATTTGACTGTAAACA CAAAGATATTAGTACAAAA

TACGTGACGTAGAAAGTAATAATTTCTTGGGTAGTTTGCAGTTTTAAAATTATGTTT TAAAATGGACTATCATATGC

TTACCGTAACTTGAAAGTATTTCGATTTCTTGGCTTTATATATCTTGTGGAAAGGAC GAAAcaccCTAGCCCGGTAA

TCCTTGAGGgTTTTAGTACTCTGGAAACAGAATCTACTAAAACAAGGCAAAATGCCG TGTTTATCTCGTCAACTTG

TTGGCGAGATTTTTGCGGCCGCAGGAACCCCTAGTGATGGAGTTGGCCACTCCCTCT CTGCGCGCTCGCTCGC

TCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGGGCTTTGCCCGGGCGGCCT CAGTGAGCGAGCGA

GCGCGCAGCTGCCTGCAGGGGCGCCTGATGCGGTATTTTCTCCTTACGCATCTGTGC GGTATTTCACACCGCAT

ACGTCAAAGCAACCATAGTACGCGCCCTGTAGCGGCGCATTAAGCGCGGCGGGTGTG GTGGTTACGCGCAGC

GTGACCGCTACACTTGCCAGCGCCTTAGCGCCCGCTCCTTTCGCTTTCTTCCCTTCC TTTCTCGCCACGTTCGC

CGGCTTTCCCCGTCAAGCTCTAAATCGGGGGCTCCCTTTAGGGTTCCGATTTAGTGC TTTACGGCACCTCGACC

CCAAAAAACTTGATTTGGGTGATGGTTCACGTAGTGGGCCATCGCCCTGATAGACGG TTTTTCGCCCTTTGACGT

TGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAACTGGAACAACACTCAACT CTATCTCGGGCTATTCTTT

TGATTTATAAGGGATTTTGCCGATTTCGGTCTATTGGTTAAAAAATGAGCTGATTTA ACAAAAATTTAACGCGAATT

TTAACAAAATATTAACGTTTACAATTTTATGGTGCACTCTCAGTACAATCTGCTCTG ATGCCGCATAGTTAAGCCA

GCCCCGACACCCGCCAACACCCGCTGACGCGCCCTGACGGGCTTGTCTGCTCCCGGC ATCCGCTTACAGACAA

GCTGTGACCGTCTCCGGGAGCTGCATGTGTCAGAGGTTTTCACCGTCATCACCGAAA CGCGCGAGACGAAAGG

GCCTCGTGATACGCCTATTTTTATAGGTTAATGTCATGATAATAATGGTTTCTTAGA CGTCAGGTGGCACTTTTCG

GGGAAATGTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTA TCCGCTCATGAGACAATAA

CCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTC CGTGTCGCCCTTATTCCCT

TTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAA AAGATGCTGAAGATCAGTT

GGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAG TTTTCGCCCCGAAGAAC

GTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTA TTGACGCCGGGCAAGAGC

AACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCA CAGAAAAGCATCTTACGG

ATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTG CGGCCAACTTACTTCTGA

CAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATG TAACTCGCCTTGATCGT

TGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCT GTAGCAATGGCAACAA

CGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAA TAGACTGGATGGAGGCG

GATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCT GATAAATCTGGAGCCGG

TGAGCGTGGAAGCCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCG TATCGTAGTTATCTACA

CGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTG CCTCACTGATTAAGCAT

TGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCAT TTTTAATTTAAAAGGATCTAG

GTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTC CACTGAGCGTCAGACCCC

GTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGC TTGCAAACAAAAAAACCAC

CGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGG TAACTGGCTTCAGCAGA

GCGCAGATACCAAATACTGTTCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAG AACTCTGTAGCACCGCCT

ACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCG TGTCTTACCGGGTTGGA

CTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTG CACACAGCCCAGCTTG

GAGCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCC ACGCTTCCCGAAGGGA

GAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGG AGCTTCCAGGGGGA

AACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGA TTTTTGTGATGCTCGTCA

GGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCC TTTTGCTGGCCTTTTG CTCACATGT pAAV-CMV-sadCas9-U6gRNA(Kcnq 2-sa sgRNA5) used in in vitro qPCR experiments (SEQ ID NO: 85)

CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCGTCGGGCGACC TTTGGTCGCCCGGCC

TCAGTGAGCGAGCGAGCGCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCC TGCGGCCTCTAGACTC

GAGGCGTTGACATTGATTATTGACTAGTTATTAATAGTAATCAATTACGGGGTCATT AGTTCATAGCCCATATATG

GAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGAC CCCCGCCCATTGACGT CAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGG TGGAGTATTTACGGT

AAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTG ACGTCAATGACGGTAAAT

GGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGT ACATCTACGTATTAGTCA

TCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAATGGGCGTGGATAGCGGT TTGACTCACGGGGATTT

CCAAGTCTCCACCCCATTGACGTCAATGGGAGTTTGTTTTGGCACCAAAATCAACGG GACTTTCCAAAATGTCGT

AACAACTCCGCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTAT ATAAGCAGAGCTCTCT

GGCTAACTACCGGTGCCACCATGGCCCCAAAGAAGAAGCGGAAGGTCGGTATCCACG GAGTCCCAGCAGCCAA

GCGGAACTACATCCTGGGCCTGGCCATCGGCATCACCAGCGTGGGCTACGGCATCAT CGACTACGAGACACGG

GACGTGATCGATGCCGGCGTGCGGCTGTTCAAAGAGGCCAACGTGGAAAACAACGAG GGCAGGCGGAGCAAG

AGAGGCGCCAGAAGGCTGAAGCGGCGGAGGCGGCATAGAATCCAGAGAGTGAAGAAG CTGCTGTTCGACTAC

AACCTGCTGACCGACCACAGCGAGCTGAGCGGCATCAACCCCTACGAGGCCAGAGTG AAGGGCCTGAGCCAG

AAGCTGAGCGAGGAAGAGTTCTCTGCCGCCCTGCTGCACCTGGCCAAGAGAAGAGGC GTGCACAACGTGAACG

AGGTGGAAGAGGACACCGGCAACGAGCTGTCCACCAAAGAGCAGATCAGCCGGAACA GCAAGGCCCTGGAAG

AGAAATACGTGGCCGAACTGCAGCTGGAACGGCTGAAGAAAGACGGCGAAGTGCGGG GCAGCATCAACAGATT

CAAGACCAGCGACTACGTGAAAGAAGCCAAACAGCTGCTGAAGGTGCAGAAGGCCTA CCACCAGCTGGACCAG

AGCTTCATCGACACCTACATCGACCTGCTGGAAACCCGGCGGACCTACTATGAGGGA CCTGGCGAGGGCAGCC

CCTTCGGCTGGAAGGACATCAAAGAATGGTACGAGATGCTGATGGGCCACTGCACCT ACTTCCCCGAGGAACT

GCGGAGCGTGAAGTACGCCTACAACGCCGACCTGTACAACGCCCTGAACGACCTGAA CAATCTCGTGATCACC

AGGGACGAGAACGAGAAGCTGGAATATTACGAGAAGTTCCAGATCATCGAGAACGTG TTCAAGCAGAAGAAGAA

GCCCACCCTGAAGCAGATCGCCAAAGAAATCCTCGTGAACGAAGAGGATATTAAGGG CTACAGAGTGACCAGCA

CCGGCAAGCCCGAGTTCACCAACCTGAAGGTGTACCACGACATCAAGGACATTACCG CCCGGAAAGAGATTATT

GAGAACGCCGAGCTGCTGGATCAGATTGCCAAGATCCTGACCATCTACCAGAGCAGC GAGGACATCCAGGAAG

AACTGACCAATCTGAACTCCGAGCTGACCCAGGAAGAGATCGAGCAGATCTCTAATC TGAAGGGCTATACCGGC

ACCCACAACCTGAGCCTGAAGGCCATCAACCTGATCCTGGACGAGCTGTGGCACACC AACGACAACCAGATCG

CTATCTTCAACCGGCTGAAGCTGGTGCCCAAGAAGGTGGACCTGTCCCAGCAGAAAG AGATCCCCACCACCCT

GGTGGACGACTTCATCCTGAGCCCCGTCGTGAAGAGAAGCTTCATCCAGAGCATCAA AGTGATCAACGCCATCA

TCAAGAAGTACGGCCTGCCCAACGACATCATTATCGAGCTGGCCCGCGAGAAGAACT CCAAGGACGCCCAGAA

AATGATCAACGAGATGCAGAAGCGGAACCGGCAGACCAACGAGCGGATCGAGGAAAT CATCCGGACCACCGGC

AAAGAGAACGCCAAGTACCTGATCGAGAAGATCAAGCTGCACGACATGCAGGAAGGC AAGTGCCTGTACAGCC

TGGAAGCCATCCCTCTGGAAGATCTGCTGAACAACCCCTTCAACTATGAGGTGGACC ACATCATCCCCAGAAGC

GTGTCCTTCGACAACAGCTTCAACAACAAGGTGCTCGTGAAGCAGGAAGAAGCCAGC AAGAAGGGCAACCGGA

CCCCATTCCAGTACCTGAGCAGCAGCGACAGCAAGATCAGCTACGAAACCTTCAAGA AGCACATCCTGAATCTG

GCCAAGGGCAAGGGCAGAATCAGCAAGACCAAGAAAGAGTATCTGCTGGAAGAACGG GACATCAACAGGTTCT

CCGTGCAGAAAGACTTCATCAACCGGAACCTGGTGGATACCAGATACGCCACCAGAG GCCTGATGAACCTGCT

GCGGAGCTACTTCAGAGTGAACAACCTGGACGTGAAAGTGAAGTCCATCAATGGCGG CTTCACCAGCTTTCTGC

GGCGGAAGTGGAAGTTTAAGAAAGAGCGGAACAAGGGGTACAAGCACCACGCCGAGG ACGCCCTGATCATTGC

CAACGCCGATTTCATCTTCAAAGAGTGGAAGAAACTGGACAAGGCCAAAAAAGTGAT GGAAAACCAGATGTTCG

AGGAAAAGCAGGCCGAGAGCATGCCCGAGATCGAAACCGAGCAGGAGTACAAAGAGA TCTTCATCACCCCCCA

CCAGATCAAGCACATTAAGGACTTCAAGGACTACAAGTACAGCCACCGGGTGGACAA GAAGCCTAATAGAGAGC

TGATTAACGACACCCTGTACTCCACCCGGAAGGACGACAAGGGCAACACCCTGATCG TGAACAATCTGAACGGC

CTGTACGACAAGGACAATGACAAGCTGAAAAAGCTGATCAACAAGAGCCCCGAAAAG CTGCTGATGTACCACCA

CGACCCCCAGACCTACCAGAAACTGAAGCTGATTATGGAACAGTACGGCGACGAGAA GAATCCCCTGTACAAGT

ACTACGAGGAAACCGGGAACTACCTGACCAAGTACTCCAAAAAGGACAACGGCCCCG TGATCAAGAAGATTAAG

TATTACGGCAACAAACTGAACGCCCATCTGGACATCACCGACGACTACCCCAACAGC AGAAACAAGGTCGTGAA

GCTGTCCCTGAAGCCCTACAGATTCGACGTGTACCTGGACAATGGCGTGTACAAGTT CGTGACCGTGAAGAATC

TGGATGTGATCAAAAAAGAAAACTACTACGAAGTGAATAGCAAGTGCTATGAGGAAG CTAAGAAGCTGAAGAAGA

TCAGCAACCAGGCCGAGTTTATCGCCTCCTTCTACAACAACGATCTGATCAAGATCA ACGGCGAGCTGTATAGA

GTGATCGGCGTGAACAACGACCTGCTGAACCGGATCGAAGTGAACATGATCGACATC ACCTACCGCGAGTACCT

GGAAAACATGAACGACAAGAGGCCCCCCAGGATCATTAAGACAATCGCCTCCAAGAC CCAGAGCATTAAGAAGT

ACAGCACAGACATTCTGGGCAACCTGTATGAAGTGAAATCTAAGAAGCACCCTCAGA TCATCAAAAAGGGCAAAA

GGCCGGCGGCCACGAAAAAGGCCGGCCAGGCAAAAAAGAAAAAGGGATCCGGACGGG CTGACGCATTGGACG

ATTTTGATCTGGATATGCTGGGAAGTGACGCCCTCGATGATTTTGACCTTGACATGC TTGGTTCGGATGCCCTTG

ATGACTTTGACCTCGACATGCTCGGCAGTGACGCCCTTGATGATTTCGACCTGGACA TGCTGATTAACTGTACAG GCAGTGGAGAGGGCAGAGGAAGTCTGCTAACATGCGGTGACGTCGAGGAGAATCCTGGCC CAATGGCCAAGC

CTTTGTCTCAAGAAGAATCCACCCTCATTGAAAGAGCAACGGCTACAATCAACAGCA TCCCCATCTCTGAAGACT

ACAGCGTCGCCAGCGCAGCTCTCTCTAGCGACGGCCGCATCTTCACTGGTGTCAATG TATATCATTTTACTGGG

GGACCTTGTGCAGAACTCGTGGTGCTGGGCACTGCTGCTGCTGCGGCAGCTGGCAAC CTGACTTGTATCGTCG

CGATCGGAAATGAGAACAGGGGCATCTTGAGCCCCTGCGGACGGTGCCGACAGGTGC TTCTCGATCTGCATCC

TGGGATCAAAGCCATAGTGAAGGACAGTGATGGACAGCCGACGGCAGTTGGGATTCG TGAATTGCTGCCCTCT

GGTTATGTGTGGGAGGGCTAAGAATTCCTAGAGCTCGCTGATCAGCCTCGACTGTGC CTTCTAGTTGCCAGCCA

TCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACT GTCCTTTCCTAATAAAAT

GAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTG GGGCAGGACAGCAAGG

GGGAGGATTGGGAAGAGAATAGCAGGCATGCTGGGGAGGTACCGAGGGCCTATTTCC CATGATTCCTTCATATT

TGCATATACGATACAAGGCTGTTAGAGAGATAATTGGAATTAATTTGACTGTAAACA CAAAGATATTAGTACAAAA

TACGTGACGTAGAAAGTAATAATTTCTTGGGTAGTTTGCAGTTTTAAAATTATGTTT TAAAATGGACTATCATATGC

TTACCGTAACTTGAAAGTATTTCGATTTCTTGGCTTTATATATCTTGTGGAAAGGAC GAAAcaccGGCAGGGCTGG

ACTCCCCCTCgTTTTAGTACTCTGGAAACAGAATCTACTAAAACAAGGCAAAATGCC GTGTTTATCTCGTCAACTT

GTTGGCGAGATTTTTGCGGCCGCAGGAACCCCTAGTGATGGAGTTGGCCACTCCCTC TCTGCGCGCTCGCTCG

CTCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGGGCTTTGCCCGGGCGGCC TCAGTGAGCGAGCG

AGCGCGCAGCTGCCTGCAGGGGCGCCTGATGCGGTATTTTCTCCTTACGCATCTGTG CGGTATTTCACACCGCA

TACGTCAAAGCAACCATAGTACGCGCCCTGTAGCGGCGCATTAAGCGCGGCGGGTGT GGTGGTTACGCGCAGC

GTGACCGCTACACTTGCCAGCGCCTTAGCGCCCGCTCCTTTCGCTTTCTTCCCTTCC TTTCTCGCCACGTTCGC

CGGCTTTCCCCGTCAAGCTCTAAATCGGGGGCTCCCTTTAGGGTTCCGATTTAGTGC TTTACGGCACCTCGACC

CCAAAAAACTTGATTTGGGTGATGGTTCACGTAGTGGGCCATCGCCCTGATAGACGG TTTTTCGCCCTTTGACGT

TGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAACTGGAACAACACTCAACT CTATCTCGGGCTATTCTTT

TGATTTATAAGGGATTTTGCCGATTTCGGTCTATTGGTTAAAAAATGAGCTGATTTA ACAAAAATTTAACGCGAATT

TTAACAAAATATTAACGTTTACAATTTTATGGTGCACTCTCAGTACAATCTGCTCTG ATGCCGCATAGTTAAGCCA

GCCCCGACACCCGCCAACACCCGCTGACGCGCCCTGACGGGCTTGTCTGCTCCCGGC ATCCGCTTACAGACAA

GCTGTGACCGTCTCCGGGAGCTGCATGTGTCAGAGGTTTTCACCGTCATCACCGAAA CGCGCGAGACGAAAGG

GCCTCGTGATACGCCTATTTTTATAGGTTAATGTCATGATAATAATGGTTTCTTAGA CGTCAGGTGGCACTTTTCG

GGGAAATGTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTA TCCGCTCATGAGACAATAA

CCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTC CGTGTCGCCCTTATTCCCT

TTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAA AAGATGCTGAAGATCAGTT

GGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAG TTTTCGCCCCGAAGAAC

GTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTA TTGACGCCGGGCAAGAGC

AACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCA CAGAAAAGCATCTTACGG

ATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTG CGGCCAACTTACTTCTGA

CAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATG TAACTCGCCTTGATCGT

TGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCT GTAGCAATGGCAACAA

CGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAA TAGACTGGATGGAGGCG

GATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCT GATAAATCTGGAGCCGG

TGAGCGTGGAAGCCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCG TATCGTAGTTATCTACA

CGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTG CCTCACTGATTAAGCAT

TGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCAT TTTTAATTTAAAAGGATCTAG

GTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTC CACTGAGCGTCAGACCCC

GTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGC TTGCAAACAAAAAAACCAC

CGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGG TAACTGGCTTCAGCAGA

GCGCAGATACCAAATACTGTTCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAG AACTCTGTAGCACCGCCT

ACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCG TGTCTTACCGGGTTGGA

CTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTG CACACAGCCCAGCTTG

GAGCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCC ACGCTTCCCGAAGGGA

GAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGG AGCTTCCAGGGGGA

AACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGA TTTTTGTGATGCTCGTCA

GGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCC TTTTGCTGGCCTTTTG

CTCACATGT pAAV-CMV-sadCas9-U6gRNA(Kcnq 2-sa sgRNA6) used in in vitro qPCR experiments (SEQ ID NO: 86)

CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCGTCGGGCGACC TTTGGTCGCCCGGCC

TCAGTGAGCGAGCGAGCGCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCC TGCGGCCTCTAGACTC

GAGGCGTTGACATTGATTATTGACTAGTTATTAATAGTAATCAATTACGGGGTCATT AGTTCATAGCCCATATATG

GAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGAC CCCCGCCCATTGACGT

CAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAAT GGGTGGAGTATTTACGGT

AAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTG ACGTCAATGACGGTAAAT

GGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGT ACATCTACGTATTAGTCA

TCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAATGGGCGTGGATAGCGGT TTGACTCACGGGGATTT

CCAAGTCTCCACCCCATTGACGTCAATGGGAGTTTGTTTTGGCACCAAAATCAACGG GACTTTCCAAAATGTCGT

AACAACTCCGCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTAT ATAAGCAGAGCTCTCT

GGCTAACTACCGGTGCCACCATGGCCCCAAAGAAGAAGCGGAAGGTCGGTATCCACG GAGTCCCAGCAGCCAA

GCGGAACTACATCCTGGGCCTGGCCATCGGCATCACCAGCGTGGGCTACGGCATCAT CGACTACGAGACACGG

GACGTGATCGATGCCGGCGTGCGGCTGTTCAAAGAGGCCAACGTGGAAAACAACGAG GGCAGGCGGAGCAAG

AGAGGCGCCAGAAGGCTGAAGCGGCGGAGGCGGCATAGAATCCAGAGAGTGAAGAAG CTGCTGTTCGACTAC

AACCTGCTGACCGACCACAGCGAGCTGAGCGGCATCAACCCCTACGAGGCCAGAGTG AAGGGCCTGAGCCAG

AAGCTGAGCGAGGAAGAGTTCTCTGCCGCCCTGCTGCACCTGGCCAAGAGAAGAGGC GTGCACAACGTGAACG

AGGTGGAAGAGGACACCGGCAACGAGCTGTCCACCAAAGAGCAGATCAGCCGGAACA GCAAGGCCCTGGAAG

AGAAATACGTGGCCGAACTGCAGCTGGAACGGCTGAAGAAAGACGGCGAAGTGCGGG GCAGCATCAACAGATT

CAAGACCAGCGACTACGTGAAAGAAGCCAAACAGCTGCTGAAGGTGCAGAAGGCCTA CCACCAGCTGGACCAG

AGCTTCATCGACACCTACATCGACCTGCTGGAAACCCGGCGGACCTACTATGAGGGA CCTGGCGAGGGCAGCC

CCTTCGGCTGGAAGGACATCAAAGAATGGTACGAGATGCTGATGGGCCACTGCACCT ACTTCCCCGAGGAACT

GCGGAGCGTGAAGTACGCCTACAACGCCGACCTGTACAACGCCCTGAACGACCTGAA CAATCTCGTGATCACC

AGGGACGAGAACGAGAAGCTGGAATATTACGAGAAGTTCCAGATCATCGAGAACGTG TTCAAGCAGAAGAAGAA

GCCCACCCTGAAGCAGATCGCCAAAGAAATCCTCGTGAACGAAGAGGATATTAAGGG CTACAGAGTGACCAGCA

CCGGCAAGCCCGAGTTCACCAACCTGAAGGTGTACCACGACATCAAGGACATTACCG CCCGGAAAGAGATTATT

GAGAACGCCGAGCTGCTGGATCAGATTGCCAAGATCCTGACCATCTACCAGAGCAGC GAGGACATCCAGGAAG

AACTGACCAATCTGAACTCCGAGCTGACCCAGGAAGAGATCGAGCAGATCTCTAATC TGAAGGGCTATACCGGC

ACCCACAACCTGAGCCTGAAGGCCATCAACCTGATCCTGGACGAGCTGTGGCACACC AACGACAACCAGATCG

CTATCTTCAACCGGCTGAAGCTGGTGCCCAAGAAGGTGGACCTGTCCCAGCAGAAAG AGATCCCCACCACCCT

GGTGGACGACTTCATCCTGAGCCCCGTCGTGAAGAGAAGCTTCATCCAGAGCATCAA AGTGATCAACGCCATCA

TCAAGAAGTACGGCCTGCCCAACGACATCATTATCGAGCTGGCCCGCGAGAAGAACT CCAAGGACGCCCAGAA

AATGATCAACGAGATGCAGAAGCGGAACCGGCAGACCAACGAGCGGATCGAGGAAAT CATCCGGACCACCGGC

AAAGAGAACGCCAAGTACCTGATCGAGAAGATCAAGCTGCACGACATGCAGGAAGGC AAGTGCCTGTACAGCC

TGGAAGCCATCCCTCTGGAAGATCTGCTGAACAACCCCTTCAACTATGAGGTGGACC ACATCATCCCCAGAAGC

GTGTCCTTCGACAACAGCTTCAACAACAAGGTGCTCGTGAAGCAGGAAGAAGCCAGC AAGAAGGGCAACCGGA

CCCCATTCCAGTACCTGAGCAGCAGCGACAGCAAGATCAGCTACGAAACCTTCAAGA AGCACATCCTGAATCTG

GCCAAGGGCAAGGGCAGAATCAGCAAGACCAAGAAAGAGTATCTGCTGGAAGAACGG GACATCAACAGGTTCT

CCGTGCAGAAAGACTTCATCAACCGGAACCTGGTGGATACCAGATACGCCACCAGAG GCCTGATGAACCTGCT

GCGGAGCTACTTCAGAGTGAACAACCTGGACGTGAAAGTGAAGTCCATCAATGGCGG CTTCACCAGCTTTCTGC

GGCGGAAGTGGAAGTTTAAGAAAGAGCGGAACAAGGGGTACAAGCACCACGCCGAGG ACGCCCTGATCATTGC

CAACGCCGATTTCATCTTCAAAGAGTGGAAGAAACTGGACAAGGCCAAAAAAGTGAT GGAAAACCAGATGTTCG

AGGAAAAGCAGGCCGAGAGCATGCCCGAGATCGAAACCGAGCAGGAGTACAAAGAGA TCTTCATCACCCCCCA

CCAGATCAAGCACATTAAGGACTTCAAGGACTACAAGTACAGCCACCGGGTGGACAA GAAGCCTAATAGAGAGC

TGATTAACGACACCCTGTACTCCACCCGGAAGGACGACAAGGGCAACACCCTGATCG TGAACAATCTGAACGGC

CTGTACGACAAGGACAATGACAAGCTGAAAAAGCTGATCAACAAGAGCCCCGAAAAG CTGCTGATGTACCACCA

CGACCCCCAGACCTACCAGAAACTGAAGCTGATTATGGAACAGTACGGCGACGAGAA GAATCCCCTGTACAAGT

ACTACGAGGAAACCGGGAACTACCTGACCAAGTACTCCAAAAAGGACAACGGCCCCG TGATCAAGAAGATTAAG

TATTACGGCAACAAACTGAACGCCCATCTGGACATCACCGACGACTACCCCAACAGC AGAAACAAGGTCGTGAA

GCTGTCCCTGAAGCCCTACAGATTCGACGTGTACCTGGACAATGGCGTGTACAAGTT CGTGACCGTGAAGAATC

TGGATGTGATCAAAAAAGAAAACTACTACGAAGTGAATAGCAAGTGCTATGAGGAAG CTAAGAAGCTGAAGAAGA

TCAGCAACCAGGCCGAGTTTATCGCCTCCTTCTACAACAACGATCTGATCAAGATCA ACGGCGAGCTGTATAGA

GTGATCGGCGTGAACAACGACCTGCTGAACCGGATCGAAGTGAACATGATCGACATC ACCTACCGCGAGTACCT GGAAAACATGAACGACAAGAGGCCCCCCAGGATCATTAAGACAATCGCCTCCAAGACCCA GAGCATTAAGAAGT

ACAGCACAGACATTCTGGGCAACCTGTATGAAGTGAAATCTAAGAAGCACCCTCAGA TCATCAAAAAGGGCAAAA

GGCCGGCGGCCACGAAAAAGGCCGGCCAGGCAAAAAAGAAAAAGGGATCCGGACGGG CTGACGCATTGGACG

ATTTTGATCTGGATATGCTGGGAAGTGACGCCCTCGATGATTTTGACCTTGACATGC TTGGTTCGGATGCCCTTG

ATGACTTTGACCTCGACATGCTCGGCAGTGACGCCCTTGATGATTTCGACCTGGACA TGCTGATTAACTGTACAG

GCAGTGGAGAGGGCAGAGGAAGTCTGCTAACATGCGGTGACGTCGAGGAGAATCCTG GCCCAATGGCCAAGC

CTTTGTCTCAAGAAGAATCCACCCTCATTGAAAGAGCAACGGCTACAATCAACAGCA TCCCCATCTCTGAAGACT

ACAGCGTCGCCAGCGCAGCTCTCTCTAGCGACGGCCGCATCTTCACTGGTGTCAATG TATATCATTTTACTGGG

GGACCTTGTGCAGAACTCGTGGTGCTGGGCACTGCTGCTGCTGCGGCAGCTGGCAAC CTGACTTGTATCGTCG

CGATCGGAAATGAGAACAGGGGCATCTTGAGCCCCTGCGGACGGTGCCGACAGGTGC TTCTCGATCTGCATCC

TGGGATCAAAGCCATAGTGAAGGACAGTGATGGACAGCCGACGGCAGTTGGGATTCG TGAATTGCTGCCCTCT

GGTTATGTGTGGGAGGGCTAAGAATTCCTAGAGCTCGCTGATCAGCCTCGACTGTGC CTTCTAGTTGCCAGCCA

TCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACT GTCCTTTCCTAATAAAAT

GAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTG GGGCAGGACAGCAAGG

GGGAGGATTGGGAAGAGAATAGCAGGCATGCTGGGGAGGTACCGAGGGCCTATTTCC CATGATTCCTTCATATT

TGCATATACGATACAAGGCTGTTAGAGAGATAATTGGAATTAATTTGACTGTAAACA CAAAGATATTAGTACAAAA

TACGTGACGTAGAAAGTAATAATTTCTTGGGTAGTTTGCAGTTTTAAAATTATGTTT TAAAATGGACTATCATATGC

TTACCGTAACTTGAAAGTATTTCGATTTCTTGGCTTTATATATCTTGTGGAAAGGAC GAAAcaccTCCTAGCCCGGT

AATCCTTGAgTTTTAGTACTCTGGAAACAGAATCTACTAAAACAAGGCAAAATGCCG TGTTTATCTCGTCAACTTG

TTGGCGAGATTTTTGCGGCCGCAGGAACCCCTAGTGATGGAGTTGGCCACTCCCTCT CTGCGCGCTCGCTCGC

TCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGGGCTTTGCCCGGGCGGCCT CAGTGAGCGAGCGA

GCGCGCAGCTGCCTGCAGGGGCGCCTGATGCGGTATTTTCTCCTTACGCATCTGTGC GGTATTTCACACCGCAT

ACGTCAAAGCAACCATAGTACGCGCCCTGTAGCGGCGCATTAAGCGCGGCGGGTGTG GTGGTTACGCGCAGC

GTGACCGCTACACTTGCCAGCGCCTTAGCGCCCGCTCCTTTCGCTTTCTTCCCTTCC TTTCTCGCCACGTTCGC

CGGCTTTCCCCGTCAAGCTCTAAATCGGGGGCTCCCTTTAGGGTTCCGATTTAGTGC TTTACGGCACCTCGACC

CCAAAAAACTTGATTTGGGTGATGGTTCACGTAGTGGGCCATCGCCCTGATAGACGG TTTTTCGCCCTTTGACGT

TGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAACTGGAACAACACTCAACT CTATCTCGGGCTATTCTTT

TGATTTATAAGGGATTTTGCCGATTTCGGTCTATTGGTTAAAAAATGAGCTGATTTA ACAAAAATTTAACGCGAATT

TTAACAAAATATTAACGTTTACAATTTTATGGTGCACTCTCAGTACAATCTGCTCTG ATGCCGCATAGTTAAGCCA

GCCCCGACACCCGCCAACACCCGCTGACGCGCCCTGACGGGCTTGTCTGCTCCCGGC ATCCGCTTACAGACAA

GCTGTGACCGTCTCCGGGAGCTGCATGTGTCAGAGGTTTTCACCGTCATCACCGAAA CGCGCGAGACGAAAGG

GCCTCGTGATACGCCTATTTTTATAGGTTAATGTCATGATAATAATGGTTTCTTAGA CGTCAGGTGGCACTTTTCG

GGGAAATGTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTA TCCGCTCATGAGACAATAA

CCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTC CGTGTCGCCCTTATTCCCT

TTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAA AAGATGCTGAAGATCAGTT

GGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAG TTTTCGCCCCGAAGAAC

GTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTA TTGACGCCGGGCAAGAGC

AACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCA CAGAAAAGCATCTTACGG

ATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTG CGGCCAACTTACTTCTGA

CAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATG TAACTCGCCTTGATCGT

TGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCT GTAGCAATGGCAACAA

CGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAA TAGACTGGATGGAGGCG

GATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCT GATAAATCTGGAGCCGG

TGAGCGTGGAAGCCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCG TATCGTAGTTATCTACA

CGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTG CCTCACTGATTAAGCAT

TGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCAT TTTTAATTTAAAAGGATCTAG

GTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTC CACTGAGCGTCAGACCCC

GTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGC TTGCAAACAAAAAAACCAC

CGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGG TAACTGGCTTCAGCAGA

GCGCAGATACCAAATACTGTTCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAG AACTCTGTAGCACCGCCT

ACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCG TGTCTTACCGGGTTGGA

CTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTG CACACAGCCCAGCTTG

GAGCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCC ACGCTTCCCGAAGGGA GAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGGAGC TTCCAGGGGGA AACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGATTT TTGTGATGCTCGTCA GGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCCTTT TGCTGGCCTTTTG

CTCACATGT

1. 6 KCNQ3

Nucleotide sequence of sasgRNA for mouse KCNQ3; sgRNA1 (SEQ ID NO: 87)

AGCGGGGCTAGGGCTAGAGCA

Nucleotide sequence of sasgRNA for mouse KCNQ3; sgRNA2 (SEQ ID NO: 88)

GCTGCTGCTACTGCCGCTGCA

Nucleotide sequence of sasgRNA for mouse KCNQ3; sgRNA3 (SEQ ID NO: 89)

CTACTGCCGCTGCAGCGGGGC pAAV-CMV-sadCas9-U6gRNA(Kcnq 3-sa sgRNA1) used in in vitro qPCR experiments (SEQ ID NO: 90)

CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCGTCGGGCGACC TTTGGTCGCCCGGCC

TCAGTGAGCGAGCGAGCGCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCC TGCGGCCTCTAGACTC

GAGGCGTTGACATTGATTATTGACTAGTTATTAATAGTAATCAATTACGGGGTCATT AGTTCATAGCCCATATATG

GAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGAC CCCCGCCCATTGACGT

CAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAAT GGGTGGAGTATTTACGGT

AAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTG ACGTCAATGACGGTAAAT

GGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGT ACATCTACGTATTAGTCA

TCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAATGGGCGTGGATAGCGGT TTGACTCACGGGGATTT

CCAAGTCTCCACCCCATTGACGTCAATGGGAGTTTGTTTTGGCACCAAAATCAACGG GACTTTCCAAAATGTCGT

AACAACTCCGCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTAT ATAAGCAGAGCTCTCT

GGCTAACTACCGGTGCCACCATGGCCCCAAAGAAGAAGCGGAAGGTCGGTATCCACG GAGTCCCAGCAGCCAA

GCGGAACTACATCCTGGGCCTGGCCATCGGCATCACCAGCGTGGGCTACGGCATCAT CGACTACGAGACACGG

GACGTGATCGATGCCGGCGTGCGGCTGTTCAAAGAGGCCAACGTGGAAAACAACGAG GGCAGGCGGAGCAAG

AGAGGCGCCAGAAGGCTGAAGCGGCGGAGGCGGCATAGAATCCAGAGAGTGAAGAAG CTGCTGTTCGACTAC

AACCTGCTGACCGACCACAGCGAGCTGAGCGGCATCAACCCCTACGAGGCCAGAGTG AAGGGCCTGAGCCAG

AAGCTGAGCGAGGAAGAGTTCTCTGCCGCCCTGCTGCACCTGGCCAAGAGAAGAGGC GTGCACAACGTGAACG

AGGTGGAAGAGGACACCGGCAACGAGCTGTCCACCAAAGAGCAGATCAGCCGGAACA GCAAGGCCCTGGAAG

AGAAATACGTGGCCGAACTGCAGCTGGAACGGCTGAAGAAAGACGGCGAAGTGCGGG GCAGCATCAACAGATT

CAAGACCAGCGACTACGTGAAAGAAGCCAAACAGCTGCTGAAGGTGCAGAAGGCCTA CCACCAGCTGGACCAG

AGCTTCATCGACACCTACATCGACCTGCTGGAAACCCGGCGGACCTACTATGAGGGA CCTGGCGAGGGCAGCC

CCTTCGGCTGGAAGGACATCAAAGAATGGTACGAGATGCTGATGGGCCACTGCACCT ACTTCCCCGAGGAACT

GCGGAGCGTGAAGTACGCCTACAACGCCGACCTGTACAACGCCCTGAACGACCTGAA CAATCTCGTGATCACC

AGGGACGAGAACGAGAAGCTGGAATATTACGAGAAGTTCCAGATCATCGAGAACGTG TTCAAGCAGAAGAAGAA

GCCCACCCTGAAGCAGATCGCCAAAGAAATCCTCGTGAACGAAGAGGATATTAAGGG CTACAGAGTGACCAGCA

CCGGCAAGCCCGAGTTCACCAACCTGAAGGTGTACCACGACATCAAGGACATTACCG CCCGGAAAGAGATTATT

GAGAACGCCGAGCTGCTGGATCAGATTGCCAAGATCCTGACCATCTACCAGAGCAGC GAGGACATCCAGGAAG

AACTGACCAATCTGAACTCCGAGCTGACCCAGGAAGAGATCGAGCAGATCTCTAATC TGAAGGGCTATACCGGC

ACCCACAACCTGAGCCTGAAGGCCATCAACCTGATCCTGGACGAGCTGTGGCACACC AACGACAACCAGATCG

CTATCTTCAACCGGCTGAAGCTGGTGCCCAAGAAGGTGGACCTGTCCCAGCAGAAAG AGATCCCCACCACCCT

GGTGGACGACTTCATCCTGAGCCCCGTCGTGAAGAGAAGCTTCATCCAGAGCATCAA AGTGATCAACGCCATCA

TCAAGAAGTACGGCCTGCCCAACGACATCATTATCGAGCTGGCCCGCGAGAAGAACT CCAAGGACGCCCAGAA

AATGATCAACGAGATGCAGAAGCGGAACCGGCAGACCAACGAGCGGATCGAGGAAAT CATCCGGACCACCGGC

AAAGAGAACGCCAAGTACCTGATCGAGAAGATCAAGCTGCACGACATGCAGGAAGGC AAGTGCCTGTACAGCC

TGGAAGCCATCCCTCTGGAAGATCTGCTGAACAACCCCTTCAACTATGAGGTGGACC ACATCATCCCCAGAAGC

GTGTCCTTCGACAACAGCTTCAACAACAAGGTGCTCGTGAAGCAGGAAGAAGCCAGC AAGAAGGGCAACCGGA CCCCATTCCAGTACCTGAGCAGCAGCGACAGCAAGATCAGCTACGAAACCTTCAAGAAGC ACATCCTGAATCTG

GCCAAGGGCAAGGGCAGAATCAGCAAGACCAAGAAAGAGTATCTGCTGGAAGAACGG GACATCAACAGGTTCT

CCGTGCAGAAAGACTTCATCAACCGGAACCTGGTGGATACCAGATACGCCACCAGAG GCCTGATGAACCTGCT

GCGGAGCTACTTCAGAGTGAACAACCTGGACGTGAAAGTGAAGTCCATCAATGGCGG CTTCACCAGCTTTCTGC

GGCGGAAGTGGAAGTTTAAGAAAGAGCGGAACAAGGGGTACAAGCACCACGCCGAGG ACGCCCTGATCATTGC

CAACGCCGATTTCATCTTCAAAGAGTGGAAGAAACTGGACAAGGCCAAAAAAGTGAT GGAAAACCAGATGTTCG

AGGAAAAGCAGGCCGAGAGCATGCCCGAGATCGAAACCGAGCAGGAGTACAAAGAGA TCTTCATCACCCCCCA

CCAGATCAAGCACATTAAGGACTTCAAGGACTACAAGTACAGCCACCGGGTGGACAA GAAGCCTAATAGAGAGC

TGATTAACGACACCCTGTACTCCACCCGGAAGGACGACAAGGGCAACACCCTGATCG TGAACAATCTGAACGGC

CTGTACGACAAGGACAATGACAAGCTGAAAAAGCTGATCAACAAGAGCCCCGAAAAG CTGCTGATGTACCACCA

CGACCCCCAGACCTACCAGAAACTGAAGCTGATTATGGAACAGTACGGCGACGAGAA GAATCCCCTGTACAAGT

ACTACGAGGAAACCGGGAACTACCTGACCAAGTACTCCAAAAAGGACAACGGCCCCG TGATCAAGAAGATTAAG

TATTACGGCAACAAACTGAACGCCCATCTGGACATCACCGACGACTACCCCAACAGC AGAAACAAGGTCGTGAA

GCTGTCCCTGAAGCCCTACAGATTCGACGTGTACCTGGACAATGGCGTGTACAAGTT CGTGACCGTGAAGAATC

TGGATGTGATCAAAAAAGAAAACTACTACGAAGTGAATAGCAAGTGCTATGAGGAAG CTAAGAAGCTGAAGAAGA

TCAGCAACCAGGCCGAGTTTATCGCCTCCTTCTACAACAACGATCTGATCAAGATCA ACGGCGAGCTGTATAGA

GTGATCGGCGTGAACAACGACCTGCTGAACCGGATCGAAGTGAACATGATCGACATC ACCTACCGCGAGTACCT

GGAAAACATGAACGACAAGAGGCCCCCCAGGATCATTAAGACAATCGCCTCCAAGAC CCAGAGCATTAAGAAGT

ACAGCACAGACATTCTGGGCAACCTGTATGAAGTGAAATCTAAGAAGCACCCTCAGA TCATCAAAAAGGGCAAAA

GGCCGGCGGCCACGAAAAAGGCCGGCCAGGCAAAAAAGAAAAAGGGATCCGGACGGG CTGACGCATTGGACG

ATTTTGATCTGGATATGCTGGGAAGTGACGCCCTCGATGATTTTGACCTTGACATGC TTGGTTCGGATGCCCTTG

ATGACTTTGACCTCGACATGCTCGGCAGTGACGCCCTTGATGATTTCGACCTGGACA TGCTGATTAACTGTACAG

GCAGTGGAGAGGGCAGAGGAAGTCTGCTAACATGCGGTGACGTCGAGGAGAATCCTG GCCCAATGGCCAAGC

CTTTGTCTCAAGAAGAATCCACCCTCATTGAAAGAGCAACGGCTACAATCAACAGCA TCCCCATCTCTGAAGACT

ACAGCGTCGCCAGCGCAGCTCTCTCTAGCGACGGCCGCATCTTCACTGGTGTCAATG TATATCATTTTACTGGG

GGACCTTGTGCAGAACTCGTGGTGCTGGGCACTGCTGCTGCTGCGGCAGCTGGCAAC CTGACTTGTATCGTCG

CGATCGGAAATGAGAACAGGGGCATCTTGAGCCCCTGCGGACGGTGCCGACAGGTGC TTCTCGATCTGCATCC

TGGGATCAAAGCCATAGTGAAGGACAGTGATGGACAGCCGACGGCAGTTGGGATTCG TGAATTGCTGCCCTCT

GGTTATGTGTGGGAGGGCTAAGAATTCCTAGAGCTCGCTGATCAGCCTCGACTGTGC CTTCTAGTTGCCAGCCA

TCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACT GTCCTTTCCTAATAAAAT

GAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTG GGGCAGGACAGCAAGG

GGGAGGATTGGGAAGAGAATAGCAGGCATGCTGGGGAGGTACCGAGGGCCTATTTCC CATGATTCCTTCATATT

TGCATATACGATACAAGGCTGTTAGAGAGATAATTGGAATTAATTTGACTGTAAACA CAAAGATATTAGTACAAAA

TACGTGACGTAGAAAGTAATAATTTCTTGGGTAGTTTGCAGTTTTAAAATTATGTTT TAAAATGGACTATCATATGC

TTACCGTAACTTGAAAGTATTTCGATTTCTTGGCTTTATATATCTTGTGGAAAGGAC GAAAcaccgAGCGGGGCTAG

GGCTAGAGCAgTTTTAGTACTCTGGAAACAGAATCTACTAAAACAAGGCAAAATGCC GTGTTTATCTCGTCAACTT

GTTGGCGAGATTTTTGCGGCCGCAGGAACCCCTAGTGATGGAGTTGGCCACTCCCTC TCTGCGCGCTCGCTCG

CTCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGGGCTTTGCCCGGGCGGCC TCAGTGAGCGAGCG

AGCGCGCAGCTGCCTGCAGGGGCGCCTGATGCGGTATTTTCTCCTTACGCATCTGTG CGGTATTTCACACCGCA

TACGTCAAAGCAACCATAGTACGCGCCCTGTAGCGGCGCATTAAGCGCGGCGGGTGT GGTGGTTACGCGCAGC

GTGACCGCTACACTTGCCAGCGCCTTAGCGCCCGCTCCTTTCGCTTTCTTCCCTTCC TTTCTCGCCACGTTCGC

CGGCTTTCCCCGTCAAGCTCTAAATCGGGGGCTCCCTTTAGGGTTCCGATTTAGTGC TTTACGGCACCTCGACC

CCAAAAAACTTGATTTGGGTGATGGTTCACGTAGTGGGCCATCGCCCTGATAGACGG TTTTTCGCCCTTTGACGT

TGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAACTGGAACAACACTCAACT CTATCTCGGGCTATTCTTT

TGATTTATAAGGGATTTTGCCGATTTCGGTCTATTGGTTAAAAAATGAGCTGATTTA ACAAAAATTTAACGCGAATT

TTAACAAAATATTAACGTTTACAATTTTATGGTGCACTCTCAGTACAATCTGCTCTG ATGCCGCATAGTTAAGCCA

GCCCCGACACCCGCCAACACCCGCTGACGCGCCCTGACGGGCTTGTCTGCTCCCGGC ATCCGCTTACAGACAA

GCTGTGACCGTCTCCGGGAGCTGCATGTGTCAGAGGTTTTCACCGTCATCACCGAAA CGCGCGAGACGAAAGG

GCCTCGTGATACGCCTATTTTTATAGGTTAATGTCATGATAATAATGGTTTCTTAGA CGTCAGGTGGCACTTTTCG

GGGAAATGTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTA TCCGCTCATGAGACAATAA

CCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTC CGTGTCGCCCTTATTCCCT

TTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAA AAGATGCTGAAGATCAGTT

GGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAG TTTTCGCCCCGAAGAAC GTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTATTG ACGCCGGGCAAGAGC

AACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCA CAGAAAAGCATCTTACGG

ATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTG CGGCCAACTTACTTCTGA

CAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATG TAACTCGCCTTGATCGT

TGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCT GTAGCAATGGCAACAA

CGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAA TAGACTGGATGGAGGCG

GATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCT GATAAATCTGGAGCCGG

TGAGCGTGGAAGCCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCG TATCGTAGTTATCTACA

CGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTG CCTCACTGATTAAGCAT

TGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCAT TTTTAATTTAAAAGGATCTAG

GTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTC CACTGAGCGTCAGACCCC

GTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGC TTGCAAACAAAAAAACCAC

CGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGG TAACTGGCTTCAGCAGA

GCGCAGATACCAAATACTGTTCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAG AACTCTGTAGCACCGCCT

ACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCG TGTCTTACCGGGTTGGA

CTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTG CACACAGCCCAGCTTG

GAGCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCC ACGCTTCCCGAAGGGA

GAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGG AGCTTCCAGGGGGA

AACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGA TTTTTGTGATGCTCGTCA

GGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCC TTTTGCTGGCCTTTTG CTCACATGT pAAV-CMV-sadCas9-U6gRNA(Kcnq 3-sa sgRNA2) used in in vitro qPCR experiments (SEQ ID NO: 91)

CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCGTCGGGCGACC TTTGGTCGCCCGGCC

TCAGTGAGCGAGCGAGCGCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCC TGCGGCCTCTAGACTC

GAGGCGTTGACATTGATTATTGACTAGTTATTAATAGTAATCAATTACGGGGTCATT AGTTCATAGCCCATATATG

GAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGAC CCCCGCCCATTGACGT

CAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAAT GGGTGGAGTATTTACGGT

AAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTG ACGTCAATGACGGTAAAT

GGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGT ACATCTACGTATTAGTCA

TCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAATGGGCGTGGATAGCGGT TTGACTCACGGGGATTT

CCAAGTCTCCACCCCATTGACGTCAATGGGAGTTTGTTTTGGCACCAAAATCAACGG GACTTTCCAAAATGTCGT

AACAACTCCGCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTAT ATAAGCAGAGCTCTCT

GGCTAACTACCGGTGCCACCATGGCCCCAAAGAAGAAGCGGAAGGTCGGTATCCACG GAGTCCCAGCAGCCAA

GCGGAACTACATCCTGGGCCTGGCCATCGGCATCACCAGCGTGGGCTACGGCATCAT CGACTACGAGACACGG

GACGTGATCGATGCCGGCGTGCGGCTGTTCAAAGAGGCCAACGTGGAAAACAACGAG GGCAGGCGGAGCAAG

AGAGGCGCCAGAAGGCTGAAGCGGCGGAGGCGGCATAGAATCCAGAGAGTGAAGAAG CTGCTGTTCGACTAC

AACCTGCTGACCGACCACAGCGAGCTGAGCGGCATCAACCCCTACGAGGCCAGAGTG AAGGGCCTGAGCCAG

AAGCTGAGCGAGGAAGAGTTCTCTGCCGCCCTGCTGCACCTGGCCAAGAGAAGAGGC GTGCACAACGTGAACG

AGGTGGAAGAGGACACCGGCAACGAGCTGTCCACCAAAGAGCAGATCAGCCGGAACA GCAAGGCCCTGGAAG

AGAAATACGTGGCCGAACTGCAGCTGGAACGGCTGAAGAAAGACGGCGAAGTGCGGG GCAGCATCAACAGATT

CAAGACCAGCGACTACGTGAAAGAAGCCAAACAGCTGCTGAAGGTGCAGAAGGCCTA CCACCAGCTGGACCAG

AGCTTCATCGACACCTACATCGACCTGCTGGAAACCCGGCGGACCTACTATGAGGGA CCTGGCGAGGGCAGCC

CCTTCGGCTGGAAGGACATCAAAGAATGGTACGAGATGCTGATGGGCCACTGCACCT ACTTCCCCGAGGAACT

GCGGAGCGTGAAGTACGCCTACAACGCCGACCTGTACAACGCCCTGAACGACCTGAA CAATCTCGTGATCACC

AGGGACGAGAACGAGAAGCTGGAATATTACGAGAAGTTCCAGATCATCGAGAACGTG TTCAAGCAGAAGAAGAA

GCCCACCCTGAAGCAGATCGCCAAAGAAATCCTCGTGAACGAAGAGGATATTAAGGG CTACAGAGTGACCAGCA

CCGGCAAGCCCGAGTTCACCAACCTGAAGGTGTACCACGACATCAAGGACATTACCG CCCGGAAAGAGATTATT

GAGAACGCCGAGCTGCTGGATCAGATTGCCAAGATCCTGACCATCTACCAGAGCAGC GAGGACATCCAGGAAG

AACTGACCAATCTGAACTCCGAGCTGACCCAGGAAGAGATCGAGCAGATCTCTAATC TGAAGGGCTATACCGGC

ACCCACAACCTGAGCCTGAAGGCCATCAACCTGATCCTGGACGAGCTGTGGCACACC AACGACAACCAGATCG

CTATCTTCAACCGGCTGAAGCTGGTGCCCAAGAAGGTGGACCTGTCCCAGCAGAAAG AGATCCCCACCACCCT

GGTGGACGACTTCATCCTGAGCCCCGTCGTGAAGAGAAGCTTCATCCAGAGCATCAA AGTGATCAACGCCATCA TCAAGAAGTACGGCCTGCCCAACGACATCATTATCGAGCTGGCCCGCGAGAAGAACTCCA AGGACGCCCAGAA

AATGATCAACGAGATGCAGAAGCGGAACCGGCAGACCAACGAGCGGATCGAGGAAAT CATCCGGACCACCGGC

AAAGAGAACGCCAAGTACCTGATCGAGAAGATCAAGCTGCACGACATGCAGGAAGGC AAGTGCCTGTACAGCC

TGGAAGCCATCCCTCTGGAAGATCTGCTGAACAACCCCTTCAACTATGAGGTGGACC ACATCATCCCCAGAAGC

GTGTCCTTCGACAACAGCTTCAACAACAAGGTGCTCGTGAAGCAGGAAGAAGCCAGC AAGAAGGGCAACCGGA

CCCCATTCCAGTACCTGAGCAGCAGCGACAGCAAGATCAGCTACGAAACCTTCAAGA AGCACATCCTGAATCTG

GCCAAGGGCAAGGGCAGAATCAGCAAGACCAAGAAAGAGTATCTGCTGGAAGAACGG GACATCAACAGGTTCT

CCGTGCAGAAAGACTTCATCAACCGGAACCTGGTGGATACCAGATACGCCACCAGAG GCCTGATGAACCTGCT

GCGGAGCTACTTCAGAGTGAACAACCTGGACGTGAAAGTGAAGTCCATCAATGGCGG CTTCACCAGCTTTCTGC

GGCGGAAGTGGAAGTTTAAGAAAGAGCGGAACAAGGGGTACAAGCACCACGCCGAGG ACGCCCTGATCATTGC

CAACGCCGATTTCATCTTCAAAGAGTGGAAGAAACTGGACAAGGCCAAAAAAGTGAT GGAAAACCAGATGTTCG

AGGAAAAGCAGGCCGAGAGCATGCCCGAGATCGAAACCGAGCAGGAGTACAAAGAGA TCTTCATCACCCCCCA

CCAGATCAAGCACATTAAGGACTTCAAGGACTACAAGTACAGCCACCGGGTGGACAA GAAGCCTAATAGAGAGC

TGATTAACGACACCCTGTACTCCACCCGGAAGGACGACAAGGGCAACACCCTGATCG TGAACAATCTGAACGGC

CTGTACGACAAGGACAATGACAAGCTGAAAAAGCTGATCAACAAGAGCCCCGAAAAG CTGCTGATGTACCACCA

CGACCCCCAGACCTACCAGAAACTGAAGCTGATTATGGAACAGTACGGCGACGAGAA GAATCCCCTGTACAAGT

ACTACGAGGAAACCGGGAACTACCTGACCAAGTACTCCAAAAAGGACAACGGCCCCG TGATCAAGAAGATTAAG

TATTACGGCAACAAACTGAACGCCCATCTGGACATCACCGACGACTACCCCAACAGC AGAAACAAGGTCGTGAA

GCTGTCCCTGAAGCCCTACAGATTCGACGTGTACCTGGACAATGGCGTGTACAAGTT CGTGACCGTGAAGAATC

TGGATGTGATCAAAAAAGAAAACTACTACGAAGTGAATAGCAAGTGCTATGAGGAAG CTAAGAAGCTGAAGAAGA

TCAGCAACCAGGCCGAGTTTATCGCCTCCTTCTACAACAACGATCTGATCAAGATCA ACGGCGAGCTGTATAGA

GTGATCGGCGTGAACAACGACCTGCTGAACCGGATCGAAGTGAACATGATCGACATC ACCTACCGCGAGTACCT

GGAAAACATGAACGACAAGAGGCCCCCCAGGATCATTAAGACAATCGCCTCCAAGAC CCAGAGCATTAAGAAGT

ACAGCACAGACATTCTGGGCAACCTGTATGAAGTGAAATCTAAGAAGCACCCTCAGA TCATCAAAAAGGGCAAAA

GGCCGGCGGCCACGAAAAAGGCCGGCCAGGCAAAAAAGAAAAAGGGATCCGGACGGG CTGACGCATTGGACG

ATTTTGATCTGGATATGCTGGGAAGTGACGCCCTCGATGATTTTGACCTTGACATGC TTGGTTCGGATGCCCTTG

ATGACTTTGACCTCGACATGCTCGGCAGTGACGCCCTTGATGATTTCGACCTGGACA TGCTGATTAACTGTACAG

GCAGTGGAGAGGGCAGAGGAAGTCTGCTAACATGCGGTGACGTCGAGGAGAATCCTG GCCCAATGGCCAAGC

CTTTGTCTCAAGAAGAATCCACCCTCATTGAAAGAGCAACGGCTACAATCAACAGCA TCCCCATCTCTGAAGACT

ACAGCGTCGCCAGCGCAGCTCTCTCTAGCGACGGCCGCATCTTCACTGGTGTCAATG TATATCATTTTACTGGG

GGACCTTGTGCAGAACTCGTGGTGCTGGGCACTGCTGCTGCTGCGGCAGCTGGCAAC CTGACTTGTATCGTCG

CGATCGGAAATGAGAACAGGGGCATCTTGAGCCCCTGCGGACGGTGCCGACAGGTGC TTCTCGATCTGCATCC

TGGGATCAAAGCCATAGTGAAGGACAGTGATGGACAGCCGACGGCAGTTGGGATTCG TGAATTGCTGCCCTCT

GGTTATGTGTGGGAGGGCTAAGAATTCCTAGAGCTCGCTGATCAGCCTCGACTGTGC CTTCTAGTTGCCAGCCA

TCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACT GTCCTTTCCTAATAAAAT

GAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTG GGGCAGGACAGCAAGG

GGGAGGATTGGGAAGAGAATAGCAGGCATGCTGGGGAGGTACCGAGGGCCTATTTCC CATGATTCCTTCATATT

TGCATATACGATACAAGGCTGTTAGAGAGATAATTGGAATTAATTTGACTGTAAACA CAAAGATATTAGTACAAAA

TACGTGACGTAGAAAGTAATAATTTCTTGGGTAGTTTGCAGTTTTAAAATTATGTTT TAAAATGGACTATCATATGC

TTACCGTAACTTGAAAGTATTTCGATTTCTTGGCTTTATATATCTTGTGGAAAGGAC GAAAcaccgGCTGCTGCTAC

TGCCGCTGCAgTTTTAGTACTCTGGAAACAGAATCTACTAAAACAAGGCAAAATGCC GTGTTTATCTCGTCAACTT

GTTGGCGAGATTTTTGCGGCCGCAGGAACCCCTAGTGATGGAGTTGGCCACTCCCTC TCTGCGCGCTCGCTCG

CTCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGGGCTTTGCCCGGGCGGCC TCAGTGAGCGAGCG

AGCGCGCAGCTGCCTGCAGGGGCGCCTGATGCGGTATTTTCTCCTTACGCATCTGTG CGGTATTTCACACCGCA

TACGTCAAAGCAACCATAGTACGCGCCCTGTAGCGGCGCATTAAGCGCGGCGGGTGT GGTGGTTACGCGCAGC

GTGACCGCTACACTTGCCAGCGCCTTAGCGCCCGCTCCTTTCGCTTTCTTCCCTTCC TTTCTCGCCACGTTCGC

CGGCTTTCCCCGTCAAGCTCTAAATCGGGGGCTCCCTTTAGGGTTCCGATTTAGTGC TTTACGGCACCTCGACC

CCAAAAAACTTGATTTGGGTGATGGTTCACGTAGTGGGCCATCGCCCTGATAGACGG TTTTTCGCCCTTTGACGT

TGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAACTGGAACAACACTCAACT CTATCTCGGGCTATTCTTT

TGATTTATAAGGGATTTTGCCGATTTCGGTCTATTGGTTAAAAAATGAGCTGATTTA ACAAAAATTTAACGCGAATT

TTAACAAAATATTAACGTTTACAATTTTATGGTGCACTCTCAGTACAATCTGCTCTG ATGCCGCATAGTTAAGCCA

GCCCCGACACCCGCCAACACCCGCTGACGCGCCCTGACGGGCTTGTCTGCTCCCGGC ATCCGCTTACAGACAA

GCTGTGACCGTCTCCGGGAGCTGCATGTGTCAGAGGTTTTCACCGTCATCACCGAAA CGCGCGAGACGAAAGG GCCTCGTGATACGCCTATTTTTATAGGTTAATGTCATGATAATAATGGTTTCTTAGACGT CAGGTGGCACTTTTCG

GGGAAATGTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTA TCCGCTCATGAGACAATAA

CCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTC CGTGTCGCCCTTATTCCCT

TTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAA AAGATGCTGAAGATCAGTT

GGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAG TTTTCGCCCCGAAGAAC

GTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTA TTGACGCCGGGCAAGAGC

AACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCA CAGAAAAGCATCTTACGG

ATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTG CGGCCAACTTACTTCTGA

CAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATG TAACTCGCCTTGATCGT

TGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCT GTAGCAATGGCAACAA

CGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAA TAGACTGGATGGAGGCG

GATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCT GATAAATCTGGAGCCGG

TGAGCGTGGAAGCCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCG TATCGTAGTTATCTACA

CGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTG CCTCACTGATTAAGCAT

TGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCAT TTTTAATTTAAAAGGATCTAG

GTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTC CACTGAGCGTCAGACCCC

GTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGC TTGCAAACAAAAAAACCAC

CGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGG TAACTGGCTTCAGCAGA

GCGCAGATACCAAATACTGTTCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAG AACTCTGTAGCACCGCCT

ACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCG TGTCTTACCGGGTTGGA

CTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTG CACACAGCCCAGCTTG

GAGCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCC ACGCTTCCCGAAGGGA

GAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGG AGCTTCCAGGGGGA

AACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGA TTTTTGTGATGCTCGTCA

GGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCC TTTTGCTGGCCTTTTG CTCACATGT pAAV-CMV-sadCas9-U6gRNA(Kcnq 3-sa sgRNA3) used in in vitro qPCR experiments (SEQ ID NO: 92)

CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCGTCGGGCGACC TTTGGTCGCCCGGCC

TCAGTGAGCGAGCGAGCGCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCC TGCGGCCTCTAGACTC

GAGGCGTTGACATTGATTATTGACTAGTTATTAATAGTAATCAATTACGGGGTCATT AGTTCATAGCCCATATATG

GAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGAC CCCCGCCCATTGACGT

CAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAAT GGGTGGAGTATTTACGGT

AAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTG ACGTCAATGACGGTAAAT

GGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGT ACATCTACGTATTAGTCA

TCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAATGGGCGTGGATAGCGGT TTGACTCACGGGGATTT

CCAAGTCTCCACCCCATTGACGTCAATGGGAGTTTGTTTTGGCACCAAAATCAACGG GACTTTCCAAAATGTCGT

AACAACTCCGCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTAT ATAAGCAGAGCTCTCT

GGCTAACTACCGGTGCCACCATGGCCCCAAAGAAGAAGCGGAAGGTCGGTATCCACG GAGTCCCAGCAGCCAA

GCGGAACTACATCCTGGGCCTGGCCATCGGCATCACCAGCGTGGGCTACGGCATCAT CGACTACGAGACACGG

GACGTGATCGATGCCGGCGTGCGGCTGTTCAAAGAGGCCAACGTGGAAAACAACGAG GGCAGGCGGAGCAAG

AGAGGCGCCAGAAGGCTGAAGCGGCGGAGGCGGCATAGAATCCAGAGAGTGAAGAAG CTGCTGTTCGACTAC

AACCTGCTGACCGACCACAGCGAGCTGAGCGGCATCAACCCCTACGAGGCCAGAGTG AAGGGCCTGAGCCAG

AAGCTGAGCGAGGAAGAGTTCTCTGCCGCCCTGCTGCACCTGGCCAAGAGAAGAGGC GTGCACAACGTGAACG

AGGTGGAAGAGGACACCGGCAACGAGCTGTCCACCAAAGAGCAGATCAGCCGGAACA GCAAGGCCCTGGAAG

AGAAATACGTGGCCGAACTGCAGCTGGAACGGCTGAAGAAAGACGGCGAAGTGCGGG GCAGCATCAACAGATT

CAAGACCAGCGACTACGTGAAAGAAGCCAAACAGCTGCTGAAGGTGCAGAAGGCCTA CCACCAGCTGGACCAG

AGCTTCATCGACACCTACATCGACCTGCTGGAAACCCGGCGGACCTACTATGAGGGA CCTGGCGAGGGCAGCC

CCTTCGGCTGGAAGGACATCAAAGAATGGTACGAGATGCTGATGGGCCACTGCACCT ACTTCCCCGAGGAACT

GCGGAGCGTGAAGTACGCCTACAACGCCGACCTGTACAACGCCCTGAACGACCTGAA CAATCTCGTGATCACC

AGGGACGAGAACGAGAAGCTGGAATATTACGAGAAGTTCCAGATCATCGAGAACGTG TTCAAGCAGAAGAAGAA

GCCCACCCTGAAGCAGATCGCCAAAGAAATCCTCGTGAACGAAGAGGATATTAAGGG CTACAGAGTGACCAGCA

CCGGCAAGCCCGAGTTCACCAACCTGAAGGTGTACCACGACATCAAGGACATTACCG CCCGGAAAGAGATTATT GAGAACGCCGAGCTGCTGGATCAGATTGCCAAGATCCTGACCATCTACCAGAGCAGCGAG GACATCCAGGAAG

AACTGACCAATCTGAACTCCGAGCTGACCCAGGAAGAGATCGAGCAGATCTCTAATC TGAAGGGCTATACCGGC

ACCCACAACCTGAGCCTGAAGGCCATCAACCTGATCCTGGACGAGCTGTGGCACACC AACGACAACCAGATCG

CTATCTTCAACCGGCTGAAGCTGGTGCCCAAGAAGGTGGACCTGTCCCAGCAGAAAG AGATCCCCACCACCCT

GGTGGACGACTTCATCCTGAGCCCCGTCGTGAAGAGAAGCTTCATCCAGAGCATCAA AGTGATCAACGCCATCA

TCAAGAAGTACGGCCTGCCCAACGACATCATTATCGAGCTGGCCCGCGAGAAGAACT CCAAGGACGCCCAGAA

AATGATCAACGAGATGCAGAAGCGGAACCGGCAGACCAACGAGCGGATCGAGGAAAT CATCCGGACCACCGGC

AAAGAGAACGCCAAGTACCTGATCGAGAAGATCAAGCTGCACGACATGCAGGAAGGC AAGTGCCTGTACAGCC

TGGAAGCCATCCCTCTGGAAGATCTGCTGAACAACCCCTTCAACTATGAGGTGGACC ACATCATCCCCAGAAGC

GTGTCCTTCGACAACAGCTTCAACAACAAGGTGCTCGTGAAGCAGGAAGAAGCCAGC AAGAAGGGCAACCGGA

CCCCATTCCAGTACCTGAGCAGCAGCGACAGCAAGATCAGCTACGAAACCTTCAAGA AGCACATCCTGAATCTG

GCCAAGGGCAAGGGCAGAATCAGCAAGACCAAGAAAGAGTATCTGCTGGAAGAACGG GACATCAACAGGTTCT

CCGTGCAGAAAGACTTCATCAACCGGAACCTGGTGGATACCAGATACGCCACCAGAG GCCTGATGAACCTGCT

GCGGAGCTACTTCAGAGTGAACAACCTGGACGTGAAAGTGAAGTCCATCAATGGCGG CTTCACCAGCTTTCTGC

GGCGGAAGTGGAAGTTTAAGAAAGAGCGGAACAAGGGGTACAAGCACCACGCCGAGG ACGCCCTGATCATTGC

CAACGCCGATTTCATCTTCAAAGAGTGGAAGAAACTGGACAAGGCCAAAAAAGTGAT GGAAAACCAGATGTTCG

AGGAAAAGCAGGCCGAGAGCATGCCCGAGATCGAAACCGAGCAGGAGTACAAAGAGA TCTTCATCACCCCCCA

CCAGATCAAGCACATTAAGGACTTCAAGGACTACAAGTACAGCCACCGGGTGGACAA GAAGCCTAATAGAGAGC

TGATTAACGACACCCTGTACTCCACCCGGAAGGACGACAAGGGCAACACCCTGATCG TGAACAATCTGAACGGC

CTGTACGACAAGGACAATGACAAGCTGAAAAAGCTGATCAACAAGAGCCCCGAAAAG CTGCTGATGTACCACCA

CGACCCCCAGACCTACCAGAAACTGAAGCTGATTATGGAACAGTACGGCGACGAGAA GAATCCCCTGTACAAGT

ACTACGAGGAAACCGGGAACTACCTGACCAAGTACTCCAAAAAGGACAACGGCCCCG TGATCAAGAAGATTAAG

TATTACGGCAACAAACTGAACGCCCATCTGGACATCACCGACGACTACCCCAACAGC AGAAACAAGGTCGTGAA

GCTGTCCCTGAAGCCCTACAGATTCGACGTGTACCTGGACAATGGCGTGTACAAGTT CGTGACCGTGAAGAATC

TGGATGTGATCAAAAAAGAAAACTACTACGAAGTGAATAGCAAGTGCTATGAGGAAG CTAAGAAGCTGAAGAAGA

TCAGCAACCAGGCCGAGTTTATCGCCTCCTTCTACAACAACGATCTGATCAAGATCA ACGGCGAGCTGTATAGA

GTGATCGGCGTGAACAACGACCTGCTGAACCGGATCGAAGTGAACATGATCGACATC ACCTACCGCGAGTACCT

GGAAAACATGAACGACAAGAGGCCCCCCAGGATCATTAAGACAATCGCCTCCAAGAC CCAGAGCATTAAGAAGT

ACAGCACAGACATTCTGGGCAACCTGTATGAAGTGAAATCTAAGAAGCACCCTCAGA TCATCAAAAAGGGCAAAA

GGCCGGCGGCCACGAAAAAGGCCGGCCAGGCAAAAAAGAAAAAGGGATCCGGACGGG CTGACGCATTGGACG

ATTTTGATCTGGATATGCTGGGAAGTGACGCCCTCGATGATTTTGACCTTGACATGC TTGGTTCGGATGCCCTTG

ATGACTTTGACCTCGACATGCTCGGCAGTGACGCCCTTGATGATTTCGACCTGGACA TGCTGATTAACTGTACAG

GCAGTGGAGAGGGCAGAGGAAGTCTGCTAACATGCGGTGACGTCGAGGAGAATCCTG GCCCAATGGCCAAGC

CTTTGTCTCAAGAAGAATCCACCCTCATTGAAAGAGCAACGGCTACAATCAACAGCA TCCCCATCTCTGAAGACT

ACAGCGTCGCCAGCGCAGCTCTCTCTAGCGACGGCCGCATCTTCACTGGTGTCAATG TATATCATTTTACTGGG

GGACCTTGTGCAGAACTCGTGGTGCTGGGCACTGCTGCTGCTGCGGCAGCTGGCAAC CTGACTTGTATCGTCG

CGATCGGAAATGAGAACAGGGGCATCTTGAGCCCCTGCGGACGGTGCCGACAGGTGC TTCTCGATCTGCATCC

TGGGATCAAAGCCATAGTGAAGGACAGTGATGGACAGCCGACGGCAGTTGGGATTCG TGAATTGCTGCCCTCT

GGTTATGTGTGGGAGGGCTAAGAATTCCTAGAGCTCGCTGATCAGCCTCGACTGTGC CTTCTAGTTGCCAGCCA

TCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACT GTCCTTTCCTAATAAAAT

GAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTG GGGCAGGACAGCAAGG

GGGAGGATTGGGAAGAGAATAGCAGGCATGCTGGGGAGGTACCGAGGGCCTATTTCC CATGATTCCTTCATATT

TGCATATACGATACAAGGCTGTTAGAGAGATAATTGGAATTAATTTGACTGTAAACA CAAAGATATTAGTACAAAA

TACGTGACGTAGAAAGTAATAATTTCTTGGGTAGTTTGCAGTTTTAAAATTATGTTT TAAAATGGACTATCATATGC

TTACCGTAACTTGAAAGTATTTCGATTTCTTGGCTTTATATATCTTGTGGAAAGGAC GAAAcaccgCTACTGCCGCT

GCAGCGGGGCgTTTTAGTACTCTGGAAACAGAATCTACTAAAACAAGGCAAAATGCC GTGTTTATCTCGTCAACT

TGTTGGCGAGATTTTTGCGGCCGCAGGAACCCCTAGTGATGGAGTTGGCCACTCCCT CTCTGCGCGCTCGCTC

GCTCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGGGCTTTGCCCGGGCGGC CTCAGTGAGCGAGC

GAGCGCGCAGCTGCCTGCAGGGGCGCCTGATGCGGTATTTTCTCCTTACGCATCTGT GCGGTATTTCACACCG

CATACGTCAAAGCAACCATAGTACGCGCCCTGTAGCGGCGCATTAAGCGCGGCGGGT GTGGTGGTTACGCGCA

GCGTGACCGCTACACTTGCCAGCGCCTTAGCGCCCGCTCCTTTCGCTTTCTTCCCTT CCTTTCTCGCCACGTTC

GCCGGCTTTCCCCGTCAAGCTCTAAATCGGGGGCTCCCTTTAGGGTTCCGATTTAGT GCTTTACGGCACCTCGA

CCCCAAAAAACTTGATTTGGGTGATGGTTCACGTAGTGGGCCATCGCCCTGATAGAC GGTTTTTCGCCCTTTGAC GTTGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAACTGGAACAACACTCAACTC TATCTCGGGCTATTCT

TTTGATTTATAAGGGATTTTGCCGATTTCGGTCTATTGGTTAAAAAATGAGCTGATT TAACAAAAATTTAACGCGAA

TTTTAACAAAATATTAACGTTTACAATTTTATGGTGCACTCTCAGTACAATCTGCTC TGATGCCGCATAGTTAAGCC

AGCCCCGACACCCGCCAACACCCGCTGACGCGCCCTGACGGGCTTGTCTGCTCCCGG CATCCGCTTACAGACA

AGCTGTGACCGTCTCCGGGAGCTGCATGTGTCAGAGGTTTTCACCGTCATCACCGAA ACGCGCGAGACGAAAG

GGCCTCGTGATACGCCTATTTTTATAGGTTAATGTCATGATAATAATGGTTTCTTAG ACGTCAGGTGGCACTTTTC

GGGGAAATGTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGT ATCCGCTCATGAGACAATA

ACCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTT CCGTGTCGCCCTTATTCCC

TTTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTA AAAGATGCTGAAGATCAGT

TGGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGA GTTTTCGCCCCGAAGAA

CGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGT ATTGACGCCGGGCAAGAG

CAACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTC ACAGAAAAGCATCTTACG

GATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACT GCGGCCAACTTACTTCTG

ACAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCAT GTAACTCGCCTTGATCG

TTGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCC TGTAGCAATGGCAACA

ACGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTA ATAGACTGGATGGAGGCG

GATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCT GATAAATCTGGAGCCGG

TGAGCGTGGAAGCCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCG TATCGTAGTTATCTACA

CGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTG CCTCACTGATTAAGCAT

TGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCAT TTTTAATTTAAAAGGATCTAG

GTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTC CACTGAGCGTCAGACCCC

GTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGC TTGCAAACAAAAAAACCAC

CGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGG TAACTGGCTTCAGCAGA

GCGCAGATACCAAATACTGTTCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAG AACTCTGTAGCACCGCCT

ACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCG TGTCTTACCGGGTTGGA

CTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTG CACACAGCCCAGCTTG

GAGCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCC ACGCTTCCCGAAGGGA

GAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGG AGCTTCCAGGGGGA

AACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGA TTTTTGTGATGCTCGTCA

GGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCC TTTTGCTGGCCTTTTG

CTCACATGT

1.7 GABRA1

Nucleotide sequence of sasgRNA for mouse GABRA1; sgRNA1 (SEQ ID NO: 93)

AATCTCCAGTGCAGGAGCACG

Nucleotide sequence of sasgRNA for mouse GABRA1; sgRNA2 (SEQ ID NO: 94)

ATTGGATATTGGGAAGCAAAT

Nucleotide sequence of sasgRNA for mouse GABRA1; sgRNA3 (SEQ ID NO: 95)

TGTATAGCTGCAGATTGGATA pAAV-CMV-sadCas9-U6gRNA(Gabra1-sa sgRNA1) used in in vitro qPCR experiments (SEQ ID NO: 96)

CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCGTCGGGCGACC TTTGGTCGCCCGGCC

TCAGTGAGCGAGCGAGCGCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCC TGCGGCCTCTAGACTC

GAGGCGTTGACATTGATTATTGACTAGTTATTAATAGTAATCAATTACGGGGTCATT AGTTCATAGCCCATATATG

GAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGAC CCCCGCCCATTGACGT

CAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAAT GGGTGGAGTATTTACGGT

AAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTG ACGTCAATGACGGTAAAT

GGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGT ACATCTACGTATTAGTCA

TCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAATGGGCGTGGATAGCGGT TTGACTCACGGGGATTT CCAAGTCTCCACCCCATTGACGTCAATGGGAGTTTGTTTTGGCACCAAAATCAACGGGAC TTTCCAAAATGTCGT

AACAACTCCGCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTAT ATAAGCAGAGCTCTCT

GGCTAACTACCGGTGCCACCATGGCCCCAAAGAAGAAGCGGAAGGTCGGTATCCACG GAGTCCCAGCAGCCAA

GCGGAACTACATCCTGGGCCTGGCCATCGGCATCACCAGCGTGGGCTACGGCATCAT CGACTACGAGACACGG

GACGTGATCGATGCCGGCGTGCGGCTGTTCAAAGAGGCCAACGTGGAAAACAACGAG GGCAGGCGGAGCAAG

AGAGGCGCCAGAAGGCTGAAGCGGCGGAGGCGGCATAGAATCCAGAGAGTGAAGAAG CTGCTGTTCGACTAC

AACCTGCTGACCGACCACAGCGAGCTGAGCGGCATCAACCCCTACGAGGCCAGAGTG AAGGGCCTGAGCCAG

AAGCTGAGCGAGGAAGAGTTCTCTGCCGCCCTGCTGCACCTGGCCAAGAGAAGAGGC GTGCACAACGTGAACG

AGGTGGAAGAGGACACCGGCAACGAGCTGTCCACCAAAGAGCAGATCAGCCGGAACA GCAAGGCCCTGGAAG

AGAAATACGTGGCCGAACTGCAGCTGGAACGGCTGAAGAAAGACGGCGAAGTGCGGG GCAGCATCAACAGATT

CAAGACCAGCGACTACGTGAAAGAAGCCAAACAGCTGCTGAAGGTGCAGAAGGCCTA CCACCAGCTGGACCAG

AGCTTCATCGACACCTACATCGACCTGCTGGAAACCCGGCGGACCTACTATGAGGGA CCTGGCGAGGGCAGCC

CCTTCGGCTGGAAGGACATCAAAGAATGGTACGAGATGCTGATGGGCCACTGCACCT ACTTCCCCGAGGAACT

GCGGAGCGTGAAGTACGCCTACAACGCCGACCTGTACAACGCCCTGAACGACCTGAA CAATCTCGTGATCACC

AGGGACGAGAACGAGAAGCTGGAATATTACGAGAAGTTCCAGATCATCGAGAACGTG TTCAAGCAGAAGAAGAA

GCCCACCCTGAAGCAGATCGCCAAAGAAATCCTCGTGAACGAAGAGGATATTAAGGG CTACAGAGTGACCAGCA

CCGGCAAGCCCGAGTTCACCAACCTGAAGGTGTACCACGACATCAAGGACATTACCG CCCGGAAAGAGATTATT

GAGAACGCCGAGCTGCTGGATCAGATTGCCAAGATCCTGACCATCTACCAGAGCAGC GAGGACATCCAGGAAG

AACTGACCAATCTGAACTCCGAGCTGACCCAGGAAGAGATCGAGCAGATCTCTAATC TGAAGGGCTATACCGGC

ACCCACAACCTGAGCCTGAAGGCCATCAACCTGATCCTGGACGAGCTGTGGCACACC AACGACAACCAGATCG

CTATCTTCAACCGGCTGAAGCTGGTGCCCAAGAAGGTGGACCTGTCCCAGCAGAAAG AGATCCCCACCACCCT

GGTGGACGACTTCATCCTGAGCCCCGTCGTGAAGAGAAGCTTCATCCAGAGCATCAA AGTGATCAACGCCATCA

TCAAGAAGTACGGCCTGCCCAACGACATCATTATCGAGCTGGCCCGCGAGAAGAACT CCAAGGACGCCCAGAA

AATGATCAACGAGATGCAGAAGCGGAACCGGCAGACCAACGAGCGGATCGAGGAAAT CATCCGGACCACCGGC

AAAGAGAACGCCAAGTACCTGATCGAGAAGATCAAGCTGCACGACATGCAGGAAGGC AAGTGCCTGTACAGCC

TGGAAGCCATCCCTCTGGAAGATCTGCTGAACAACCCCTTCAACTATGAGGTGGACC ACATCATCCCCAGAAGC

GTGTCCTTCGACAACAGCTTCAACAACAAGGTGCTCGTGAAGCAGGAAGAAGCCAGC AAGAAGGGCAACCGGA

CCCCATTCCAGTACCTGAGCAGCAGCGACAGCAAGATCAGCTACGAAACCTTCAAGA AGCACATCCTGAATCTG

GCCAAGGGCAAGGGCAGAATCAGCAAGACCAAGAAAGAGTATCTGCTGGAAGAACGG GACATCAACAGGTTCT

CCGTGCAGAAAGACTTCATCAACCGGAACCTGGTGGATACCAGATACGCCACCAGAG GCCTGATGAACCTGCT

GCGGAGCTACTTCAGAGTGAACAACCTGGACGTGAAAGTGAAGTCCATCAATGGCGG CTTCACCAGCTTTCTGC

GGCGGAAGTGGAAGTTTAAGAAAGAGCGGAACAAGGGGTACAAGCACCACGCCGAGG ACGCCCTGATCATTGC

CAACGCCGATTTCATCTTCAAAGAGTGGAAGAAACTGGACAAGGCCAAAAAAGTGAT GGAAAACCAGATGTTCG

AGGAAAAGCAGGCCGAGAGCATGCCCGAGATCGAAACCGAGCAGGAGTACAAAGAGA TCTTCATCACCCCCCA

CCAGATCAAGCACATTAAGGACTTCAAGGACTACAAGTACAGCCACCGGGTGGACAA GAAGCCTAATAGAGAGC

TGATTAACGACACCCTGTACTCCACCCGGAAGGACGACAAGGGCAACACCCTGATCG TGAACAATCTGAACGGC

CTGTACGACAAGGACAATGACAAGCTGAAAAAGCTGATCAACAAGAGCCCCGAAAAG CTGCTGATGTACCACCA

CGACCCCCAGACCTACCAGAAACTGAAGCTGATTATGGAACAGTACGGCGACGAGAA GAATCCCCTGTACAAGT

ACTACGAGGAAACCGGGAACTACCTGACCAAGTACTCCAAAAAGGACAACGGCCCCG TGATCAAGAAGATTAAG

TATTACGGCAACAAACTGAACGCCCATCTGGACATCACCGACGACTACCCCAACAGC AGAAACAAGGTCGTGAA

GCTGTCCCTGAAGCCCTACAGATTCGACGTGTACCTGGACAATGGCGTGTACAAGTT CGTGACCGTGAAGAATC

TGGATGTGATCAAAAAAGAAAACTACTACGAAGTGAATAGCAAGTGCTATGAGGAAG CTAAGAAGCTGAAGAAGA

TCAGCAACCAGGCCGAGTTTATCGCCTCCTTCTACAACAACGATCTGATCAAGATCA ACGGCGAGCTGTATAGA

GTGATCGGCGTGAACAACGACCTGCTGAACCGGATCGAAGTGAACATGATCGACATC ACCTACCGCGAGTACCT

GGAAAACATGAACGACAAGAGGCCCCCCAGGATCATTAAGACAATCGCCTCCAAGAC CCAGAGCATTAAGAAGT

ACAGCACAGACATTCTGGGCAACCTGTATGAAGTGAAATCTAAGAAGCACCCTCAGA TCATCAAAAAGGGCAAAA

GGCCGGCGGCCACGAAAAAGGCCGGCCAGGCAAAAAAGAAAAAGGGATCCGGACGGG CTGACGCATTGGACG

ATTTTGATCTGGATATGCTGGGAAGTGACGCCCTCGATGATTTTGACCTTGACATGC TTGGTTCGGATGCCCTTG

ATGACTTTGACCTCGACATGCTCGGCAGTGACGCCCTTGATGATTTCGACCTGGACA TGCTGATTAACTGTACAG

GCAGTGGAGAGGGCAGAGGAAGTCTGCTAACATGCGGTGACGTCGAGGAGAATCCTG GCCCAATGGCCAAGC

CTTTGTCTCAAGAAGAATCCACCCTCATTGAAAGAGCAACGGCTACAATCAACAGCA TCCCCATCTCTGAAGACT

ACAGCGTCGCCAGCGCAGCTCTCTCTAGCGACGGCCGCATCTTCACTGGTGTCAATG TATATCATTTTACTGGG

GGACCTTGTGCAGAACTCGTGGTGCTGGGCACTGCTGCTGCTGCGGCAGCTGGCAAC CTGACTTGTATCGTCG CGATCGGAAATGAGAACAGGGGCATCTTGAGCCCCTGCGGACGGTGCCGACAGGTGCTTC TCGATCTGCATCC

TGGGATCAAAGCCATAGTGAAGGACAGTGATGGACAGCCGACGGCAGTTGGGATTCG TGAATTGCTGCCCTCT

GGTTATGTGTGGGAGGGCTAAGAATTCCTAGAGCTCGCTGATCAGCCTCGACTGTGC CTTCTAGTTGCCAGCCA

TCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACT GTCCTTTCCTAATAAAAT

GAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTG GGGCAGGACAGCAAGG

GGGAGGATTGGGAAGAGAATAGCAGGCATGCTGGGGAGGTACCGAGGGCCTATTTCC CATGATTCCTTCATATT

TGCATATACGATACAAGGCTGTTAGAGAGATAATTGGAATTAATTTGACTGTAAACA CAAAGATATTAGTACAAAA

TACGTGACGTAGAAAGTAATAATTTCTTGGGTAGTTTGCAGTTTTAAAATTATGTTT TAAAATGGACTATCATATGC

TTACCGTAACTTGAAAGTATTTCGATTTCTTGGCTTTATATATCTTGTGGAAAGGAC GAAAcaccgAATCTCCAGTG

CAGGAGCACGgTTTTAGTACTCTGGAAACAGAATCTACTAAAACAAGGCAAAATGCC GTGTTTATCTCGTCAACTT

GTTGGCGAGATTTTTGCGGCCGCAGGAACCCCTAGTGATGGAGTTGGCCACTCCCTC TCTGCGCGCTCGCTCG

CTCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGGGCTTTGCCCGGGCGGCC TCAGTGAGCGAGCG

AGCGCGCAGCTGCCTGCAGGGGCGCCTGATGCGGTATTTTCTCCTTACGCATCTGTG CGGTATTTCACACCGCA

TACGTCAAAGCAACCATAGTACGCGCCCTGTAGCGGCGCATTAAGCGCGGCGGGTGT GGTGGTTACGCGCAGC

GTGACCGCTACACTTGCCAGCGCCTTAGCGCCCGCTCCTTTCGCTTTCTTCCCTTCC TTTCTCGCCACGTTCGC

CGGCTTTCCCCGTCAAGCTCTAAATCGGGGGCTCCCTTTAGGGTTCCGATTTAGTGC TTTACGGCACCTCGACC

CCAAAAAACTTGATTTGGGTGATGGTTCACGTAGTGGGCCATCGCCCTGATAGACGG TTTTTCGCCCTTTGACGT

TGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAACTGGAACAACACTCAACT CTATCTCGGGCTATTCTTT

TGATTTATAAGGGATTTTGCCGATTTCGGTCTATTGGTTAAAAAATGAGCTGATTTA ACAAAAATTTAACGCGAATT

TTAACAAAATATTAACGTTTACAATTTTATGGTGCACTCTCAGTACAATCTGCTCTG ATGCCGCATAGTTAAGCCA

GCCCCGACACCCGCCAACACCCGCTGACGCGCCCTGACGGGCTTGTCTGCTCCCGGC ATCCGCTTACAGACAA

GCTGTGACCGTCTCCGGGAGCTGCATGTGTCAGAGGTTTTCACCGTCATCACCGAAA CGCGCGAGACGAAAGG

GCCTCGTGATACGCCTATTTTTATAGGTTAATGTCATGATAATAATGGTTTCTTAGA CGTCAGGTGGCACTTTTCG

GGGAAATGTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTA TCCGCTCATGAGACAATAA

CCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTC CGTGTCGCCCTTATTCCCT

TTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAA AAGATGCTGAAGATCAGTT

GGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAG TTTTCGCCCCGAAGAAC

GTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTA TTGACGCCGGGCAAGAGC

AACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCA CAGAAAAGCATCTTACGG

ATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTG CGGCCAACTTACTTCTGA

CAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATG TAACTCGCCTTGATCGT

TGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCT GTAGCAATGGCAACAA

CGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAA TAGACTGGATGGAGGCG

GATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCT GATAAATCTGGAGCCGG

TGAGCGTGGAAGCCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCG TATCGTAGTTATCTACA

CGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTG CCTCACTGATTAAGCAT

TGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCAT TTTTAATTTAAAAGGATCTAG

GTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTC CACTGAGCGTCAGACCCC

GTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGC TTGCAAACAAAAAAACCAC

CGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGG TAACTGGCTTCAGCAGA

GCGCAGATACCAAATACTGTTCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAG AACTCTGTAGCACCGCCT

ACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCG TGTCTTACCGGGTTGGA

CTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTG CACACAGCCCAGCTTG

GAGCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCC ACGCTTCCCGAAGGGA

GAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGG AGCTTCCAGGGGGA

AACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGA TTTTTGTGATGCTCGTCA

GGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCC TTTTGCTGGCCTTTTG

CTCACATGT pAAV-CMV-sadCas9-U6gRNA(Gabra1-sa sgRNA2) used in in vitro qPCR experiments (SEQ ID NO: 97)

CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCGTCGGGCGACC TTTGGTCGCCCGGCC

TCAGTGAGCGAGCGAGCGCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCC TGCGGCCTCTAGACTC

GAGGCGTTGACATTGATTATTGACTAGTTATTAATAGTAATCAATTACGGGGTCATT AGTTCATAGCCCATATATG GAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCC CGCCCATTGACGT

CAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAAT GGGTGGAGTATTTACGGT

AAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTG ACGTCAATGACGGTAAAT

GGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGT ACATCTACGTATTAGTCA

TCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAATGGGCGTGGATAGCGGT TTGACTCACGGGGATTT

CCAAGTCTCCACCCCATTGACGTCAATGGGAGTTTGTTTTGGCACCAAAATCAACGG GACTTTCCAAAATGTCGT

AACAACTCCGCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTAT ATAAGCAGAGCTCTCT

GGCTAACTACCGGTGCCACCATGGCCCCAAAGAAGAAGCGGAAGGTCGGTATCCACG GAGTCCCAGCAGCCAA

GCGGAACTACATCCTGGGCCTGGCCATCGGCATCACCAGCGTGGGCTACGGCATCAT CGACTACGAGACACGG

GACGTGATCGATGCCGGCGTGCGGCTGTTCAAAGAGGCCAACGTGGAAAACAACGAG GGCAGGCGGAGCAAG

AGAGGCGCCAGAAGGCTGAAGCGGCGGAGGCGGCATAGAATCCAGAGAGTGAAGAAG CTGCTGTTCGACTAC

AACCTGCTGACCGACCACAGCGAGCTGAGCGGCATCAACCCCTACGAGGCCAGAGTG AAGGGCCTGAGCCAG

AAGCTGAGCGAGGAAGAGTTCTCTGCCGCCCTGCTGCACCTGGCCAAGAGAAGAGGC GTGCACAACGTGAACG

AGGTGGAAGAGGACACCGGCAACGAGCTGTCCACCAAAGAGCAGATCAGCCGGAACA GCAAGGCCCTGGAAG

AGAAATACGTGGCCGAACTGCAGCTGGAACGGCTGAAGAAAGACGGCGAAGTGCGGG GCAGCATCAACAGATT

CAAGACCAGCGACTACGTGAAAGAAGCCAAACAGCTGCTGAAGGTGCAGAAGGCCTA CCACCAGCTGGACCAG

AGCTTCATCGACACCTACATCGACCTGCTGGAAACCCGGCGGACCTACTATGAGGGA CCTGGCGAGGGCAGCC

CCTTCGGCTGGAAGGACATCAAAGAATGGTACGAGATGCTGATGGGCCACTGCACCT ACTTCCCCGAGGAACT

GCGGAGCGTGAAGTACGCCTACAACGCCGACCTGTACAACGCCCTGAACGACCTGAA CAATCTCGTGATCACC

AGGGACGAGAACGAGAAGCTGGAATATTACGAGAAGTTCCAGATCATCGAGAACGTG TTCAAGCAGAAGAAGAA

GCCCACCCTGAAGCAGATCGCCAAAGAAATCCTCGTGAACGAAGAGGATATTAAGGG CTACAGAGTGACCAGCA

CCGGCAAGCCCGAGTTCACCAACCTGAAGGTGTACCACGACATCAAGGACATTACCG CCCGGAAAGAGATTATT

GAGAACGCCGAGCTGCTGGATCAGATTGCCAAGATCCTGACCATCTACCAGAGCAGC GAGGACATCCAGGAAG

AACTGACCAATCTGAACTCCGAGCTGACCCAGGAAGAGATCGAGCAGATCTCTAATC TGAAGGGCTATACCGGC

ACCCACAACCTGAGCCTGAAGGCCATCAACCTGATCCTGGACGAGCTGTGGCACACC AACGACAACCAGATCG

CTATCTTCAACCGGCTGAAGCTGGTGCCCAAGAAGGTGGACCTGTCCCAGCAGAAAG AGATCCCCACCACCCT

GGTGGACGACTTCATCCTGAGCCCCGTCGTGAAGAGAAGCTTCATCCAGAGCATCAA AGTGATCAACGCCATCA

TCAAGAAGTACGGCCTGCCCAACGACATCATTATCGAGCTGGCCCGCGAGAAGAACT CCAAGGACGCCCAGAA

AATGATCAACGAGATGCAGAAGCGGAACCGGCAGACCAACGAGCGGATCGAGGAAAT CATCCGGACCACCGGC

AAAGAGAACGCCAAGTACCTGATCGAGAAGATCAAGCTGCACGACATGCAGGAAGGC AAGTGCCTGTACAGCC

TGGAAGCCATCCCTCTGGAAGATCTGCTGAACAACCCCTTCAACTATGAGGTGGACC ACATCATCCCCAGAAGC

GTGTCCTTCGACAACAGCTTCAACAACAAGGTGCTCGTGAAGCAGGAAGAAGCCAGC AAGAAGGGCAACCGGA

CCCCATTCCAGTACCTGAGCAGCAGCGACAGCAAGATCAGCTACGAAACCTTCAAGA AGCACATCCTGAATCTG

GCCAAGGGCAAGGGCAGAATCAGCAAGACCAAGAAAGAGTATCTGCTGGAAGAACGG GACATCAACAGGTTCT

CCGTGCAGAAAGACTTCATCAACCGGAACCTGGTGGATACCAGATACGCCACCAGAG GCCTGATGAACCTGCT

GCGGAGCTACTTCAGAGTGAACAACCTGGACGTGAAAGTGAAGTCCATCAATGGCGG CTTCACCAGCTTTCTGC

GGCGGAAGTGGAAGTTTAAGAAAGAGCGGAACAAGGGGTACAAGCACCACGCCGAGG ACGCCCTGATCATTGC

CAACGCCGATTTCATCTTCAAAGAGTGGAAGAAACTGGACAAGGCCAAAAAAGTGAT GGAAAACCAGATGTTCG

AGGAAAAGCAGGCCGAGAGCATGCCCGAGATCGAAACCGAGCAGGAGTACAAAGAGA TCTTCATCACCCCCCA

CCAGATCAAGCACATTAAGGACTTCAAGGACTACAAGTACAGCCACCGGGTGGACAA GAAGCCTAATAGAGAGC

TGATTAACGACACCCTGTACTCCACCCGGAAGGACGACAAGGGCAACACCCTGATCG TGAACAATCTGAACGGC

CTGTACGACAAGGACAATGACAAGCTGAAAAAGCTGATCAACAAGAGCCCCGAAAAG CTGCTGATGTACCACCA

CGACCCCCAGACCTACCAGAAACTGAAGCTGATTATGGAACAGTACGGCGACGAGAA GAATCCCCTGTACAAGT

ACTACGAGGAAACCGGGAACTACCTGACCAAGTACTCCAAAAAGGACAACGGCCCCG TGATCAAGAAGATTAAG

TATTACGGCAACAAACTGAACGCCCATCTGGACATCACCGACGACTACCCCAACAGC AGAAACAAGGTCGTGAA

GCTGTCCCTGAAGCCCTACAGATTCGACGTGTACCTGGACAATGGCGTGTACAAGTT CGTGACCGTGAAGAATC

TGGATGTGATCAAAAAAGAAAACTACTACGAAGTGAATAGCAAGTGCTATGAGGAAG CTAAGAAGCTGAAGAAGA

TCAGCAACCAGGCCGAGTTTATCGCCTCCTTCTACAACAACGATCTGATCAAGATCA ACGGCGAGCTGTATAGA

GTGATCGGCGTGAACAACGACCTGCTGAACCGGATCGAAGTGAACATGATCGACATC ACCTACCGCGAGTACCT

GGAAAACATGAACGACAAGAGGCCCCCCAGGATCATTAAGACAATCGCCTCCAAGAC CCAGAGCATTAAGAAGT

ACAGCACAGACATTCTGGGCAACCTGTATGAAGTGAAATCTAAGAAGCACCCTCAGA TCATCAAAAAGGGCAAAA

GGCCGGCGGCCACGAAAAAGGCCGGCCAGGCAAAAAAGAAAAAGGGATCCGGACGGG CTGACGCATTGGACG

ATTTTGATCTGGATATGCTGGGAAGTGACGCCCTCGATGATTTTGACCTTGACATGC TTGGTTCGGATGCCCTTG ATGACTTTGACCTCGACATGCTCGGCAGTGACGCCCTTGATGATTTCGACCTGGACATGC TGATTAACTGTACAG

GCAGTGGAGAGGGCAGAGGAAGTCTGCTAACATGCGGTGACGTCGAGGAGAATCCTG GCCCAATGGCCAAGC

CTTTGTCTCAAGAAGAATCCACCCTCATTGAAAGAGCAACGGCTACAATCAACAGCA TCCCCATCTCTGAAGACT

ACAGCGTCGCCAGCGCAGCTCTCTCTAGCGACGGCCGCATCTTCACTGGTGTCAATG TATATCATTTTACTGGG

GGACCTTGTGCAGAACTCGTGGTGCTGGGCACTGCTGCTGCTGCGGCAGCTGGCAAC CTGACTTGTATCGTCG

CGATCGGAAATGAGAACAGGGGCATCTTGAGCCCCTGCGGACGGTGCCGACAGGTGC TTCTCGATCTGCATCC

TGGGATCAAAGCCATAGTGAAGGACAGTGATGGACAGCCGACGGCAGTTGGGATTCG TGAATTGCTGCCCTCT

GGTTATGTGTGGGAGGGCTAAGAATTCCTAGAGCTCGCTGATCAGCCTCGACTGTGC CTTCTAGTTGCCAGCCA

TCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACT GTCCTTTCCTAATAAAAT

GAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTG GGGCAGGACAGCAAGG

GGGAGGATTGGGAAGAGAATAGCAGGCATGCTGGGGAGGTACCGAGGGCCTATTTCC CATGATTCCTTCATATT

TGCATATACGATACAAGGCTGTTAGAGAGATAATTGGAATTAATTTGACTGTAAACA CAAAGATATTAGTACAAAA

TACGTGACGTAGAAAGTAATAATTTCTTGGGTAGTTTGCAGTTTTAAAATTATGTTT TAAAATGGACTATCATATGC

TTACCGTAACTTGAAAGTATTTCGATTTCTTGGCTTTATATATCTTGTGGAAAGGAC GAAAcaccgATTGGATATTGG

GAAGCAAATgTTTTAGTACTCTGGAAACAGAATCTACTAAAACAAGGCAAAATGCCG TGTTTATCTCGTCAACTTG

TTGGCGAGATTTTTGCGGCCGCAGGAACCCCTAGTGATGGAGTTGGCCACTCCCTCT CTGCGCGCTCGCTCGC

TCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGGGCTTTGCCCGGGCGGCCT CAGTGAGCGAGCGA

GCGCGCAGCTGCCTGCAGGGGCGCCTGATGCGGTATTTTCTCCTTACGCATCTGTGC GGTATTTCACACCGCAT

ACGTCAAAGCAACCATAGTACGCGCCCTGTAGCGGCGCATTAAGCGCGGCGGGTGTG GTGGTTACGCGCAGC

GTGACCGCTACACTTGCCAGCGCCTTAGCGCCCGCTCCTTTCGCTTTCTTCCCTTCC TTTCTCGCCACGTTCGC

CGGCTTTCCCCGTCAAGCTCTAAATCGGGGGCTCCCTTTAGGGTTCCGATTTAGTGC TTTACGGCACCTCGACC

CCAAAAAACTTGATTTGGGTGATGGTTCACGTAGTGGGCCATCGCCCTGATAGACGG TTTTTCGCCCTTTGACGT

TGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAACTGGAACAACACTCAACT CTATCTCGGGCTATTCTTT

TGATTTATAAGGGATTTTGCCGATTTCGGTCTATTGGTTAAAAAATGAGCTGATTTA ACAAAAATTTAACGCGAATT

TTAACAAAATATTAACGTTTACAATTTTATGGTGCACTCTCAGTACAATCTGCTCTG ATGCCGCATAGTTAAGCCA

GCCCCGACACCCGCCAACACCCGCTGACGCGCCCTGACGGGCTTGTCTGCTCCCGGC ATCCGCTTACAGACAA

GCTGTGACCGTCTCCGGGAGCTGCATGTGTCAGAGGTTTTCACCGTCATCACCGAAA CGCGCGAGACGAAAGG

GCCTCGTGATACGCCTATTTTTATAGGTTAATGTCATGATAATAATGGTTTCTTAGA CGTCAGGTGGCACTTTTCG

GGGAAATGTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTA TCCGCTCATGAGACAATAA

CCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTC CGTGTCGCCCTTATTCCCT

TTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAA AAGATGCTGAAGATCAGTT

GGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAG TTTTCGCCCCGAAGAAC

GTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTA TTGACGCCGGGCAAGAGC

AACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCA CAGAAAAGCATCTTACGG

ATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTG CGGCCAACTTACTTCTGA

CAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATG TAACTCGCCTTGATCGT

TGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCT GTAGCAATGGCAACAA

CGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAA TAGACTGGATGGAGGCG

GATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCT GATAAATCTGGAGCCGG

TGAGCGTGGAAGCCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCG TATCGTAGTTATCTACA

CGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTG CCTCACTGATTAAGCAT

TGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCAT TTTTAATTTAAAAGGATCTAG

GTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTC CACTGAGCGTCAGACCCC

GTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGC TTGCAAACAAAAAAACCAC

CGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGG TAACTGGCTTCAGCAGA

GCGCAGATACCAAATACTGTTCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAG AACTCTGTAGCACCGCCT

ACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCG TGTCTTACCGGGTTGGA

CTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTG CACACAGCCCAGCTTG

GAGCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCC ACGCTTCCCGAAGGGA

GAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGG AGCTTCCAGGGGGA

AACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGA TTTTTGTGATGCTCGTCA

GGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCC TTTTGCTGGCCTTTTG

CTCACATGT pAAV-CMV-sadCas9-U6gRNA(Gabra1-sa sgRRA3) used in in vitro qPCR experiments (SEQ ID NO: 98)

CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCGTCGGGCGACC TTTGGTCGCCCGGCC

TCAGTGAGCGAGCGAGCGCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCC TGCGGCCTCTAGACTC

GAGGCGTTGACATTGATTATTGACTAGTTATTAATAGTAATCAATTACGGGGTCATT AGTTCATAGCCCATATATG

GAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGAC CCCCGCCCATTGACGT

CAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAAT GGGTGGAGTATTTACGGT

AAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTG ACGTCAATGACGGTAAAT

GGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGT ACATCTACGTATTAGTCA

TCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAATGGGCGTGGATAGCGGT TTGACTCACGGGGATTT

CCAAGTCTCCACCCCATTGACGTCAATGGGAGTTTGTTTTGGCACCAAAATCAACGG GACTTTCCAAAATGTCGT

AACAACTCCGCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTAT ATAAGCAGAGCTCTCT

GGCTAACTACCGGTGCCACCATGGCCCCAAAGAAGAAGCGGAAGGTCGGTATCCACG GAGTCCCAGCAGCCAA

GCGGAACTACATCCTGGGCCTGGCCATCGGCATCACCAGCGTGGGCTACGGCATCAT CGACTACGAGACACGG

GACGTGATCGATGCCGGCGTGCGGCTGTTCAAAGAGGCCAACGTGGAAAACAACGAG GGCAGGCGGAGCAAG

AGAGGCGCCAGAAGGCTGAAGCGGCGGAGGCGGCATAGAATCCAGAGAGTGAAGAAG CTGCTGTTCGACTAC

AACCTGCTGACCGACCACAGCGAGCTGAGCGGCATCAACCCCTACGAGGCCAGAGTG AAGGGCCTGAGCCAG

AAGCTGAGCGAGGAAGAGTTCTCTGCCGCCCTGCTGCACCTGGCCAAGAGAAGAGGC GTGCACAACGTGAACG

AGGTGGAAGAGGACACCGGCAACGAGCTGTCCACCAAAGAGCAGATCAGCCGGAACA GCAAGGCCCTGGAAG

AGAAATACGTGGCCGAACTGCAGCTGGAACGGCTGAAGAAAGACGGCGAAGTGCGGG GCAGCATCAACAGATT

CAAGACCAGCGACTACGTGAAAGAAGCCAAACAGCTGCTGAAGGTGCAGAAGGCCTA CCACCAGCTGGACCAG

AGCTTCATCGACACCTACATCGACCTGCTGGAAACCCGGCGGACCTACTATGAGGGA CCTGGCGAGGGCAGCC

CCTTCGGCTGGAAGGACATCAAAGAATGGTACGAGATGCTGATGGGCCACTGCACCT ACTTCCCCGAGGAACT

GCGGAGCGTGAAGTACGCCTACAACGCCGACCTGTACAACGCCCTGAACGACCTGAA CAATCTCGTGATCACC

AGGGACGAGAACGAGAAGCTGGAATATTACGAGAAGTTCCAGATCATCGAGAACGTG TTCAAGCAGAAGAAGAA

GCCCACCCTGAAGCAGATCGCCAAAGAAATCCTCGTGAACGAAGAGGATATTAAGGG CTACAGAGTGACCAGCA

CCGGCAAGCCCGAGTTCACCAACCTGAAGGTGTACCACGACATCAAGGACATTACCG CCCGGAAAGAGATTATT

GAGAACGCCGAGCTGCTGGATCAGATTGCCAAGATCCTGACCATCTACCAGAGCAGC GAGGACATCCAGGAAG

AACTGACCAATCTGAACTCCGAGCTGACCCAGGAAGAGATCGAGCAGATCTCTAATC TGAAGGGCTATACCGGC

ACCCACAACCTGAGCCTGAAGGCCATCAACCTGATCCTGGACGAGCTGTGGCACACC AACGACAACCAGATCG

CTATCTTCAACCGGCTGAAGCTGGTGCCCAAGAAGGTGGACCTGTCCCAGCAGAAAG AGATCCCCACCACCCT

GGTGGACGACTTCATCCTGAGCCCCGTCGTGAAGAGAAGCTTCATCCAGAGCATCAA AGTGATCAACGCCATCA

TCAAGAAGTACGGCCTGCCCAACGACATCATTATCGAGCTGGCCCGCGAGAAGAACT CCAAGGACGCCCAGAA

AATGATCAACGAGATGCAGAAGCGGAACCGGCAGACCAACGAGCGGATCGAGGAAAT CATCCGGACCACCGGC

AAAGAGAACGCCAAGTACCTGATCGAGAAGATCAAGCTGCACGACATGCAGGAAGGC AAGTGCCTGTACAGCC

TGGAAGCCATCCCTCTGGAAGATCTGCTGAACAACCCCTTCAACTATGAGGTGGACC ACATCATCCCCAGAAGC

GTGTCCTTCGACAACAGCTTCAACAACAAGGTGCTCGTGAAGCAGGAAGAAGCCAGC AAGAAGGGCAACCGGA

CCCCATTCCAGTACCTGAGCAGCAGCGACAGCAAGATCAGCTACGAAACCTTCAAGA AGCACATCCTGAATCTG

GCCAAGGGCAAGGGCAGAATCAGCAAGACCAAGAAAGAGTATCTGCTGGAAGAACGG GACATCAACAGGTTCT

CCGTGCAGAAAGACTTCATCAACCGGAACCTGGTGGATACCAGATACGCCACCAGAG GCCTGATGAACCTGCT

GCGGAGCTACTTCAGAGTGAACAACCTGGACGTGAAAGTGAAGTCCATCAATGGCGG CTTCACCAGCTTTCTGC

GGCGGAAGTGGAAGTTTAAGAAAGAGCGGAACAAGGGGTACAAGCACCACGCCGAGG ACGCCCTGATCATTGC

CAACGCCGATTTCATCTTCAAAGAGTGGAAGAAACTGGACAAGGCCAAAAAAGTGAT GGAAAACCAGATGTTCG

AGGAAAAGCAGGCCGAGAGCATGCCCGAGATCGAAACCGAGCAGGAGTACAAAGAGA TCTTCATCACCCCCCA

CCAGATCAAGCACATTAAGGACTTCAAGGACTACAAGTACAGCCACCGGGTGGACAA GAAGCCTAATAGAGAGC

TGATTAACGACACCCTGTACTCCACCCGGAAGGACGACAAGGGCAACACCCTGATCG TGAACAATCTGAACGGC

CTGTACGACAAGGACAATGACAAGCTGAAAAAGCTGATCAACAAGAGCCCCGAAAAG CTGCTGATGTACCACCA

CGACCCCCAGACCTACCAGAAACTGAAGCTGATTATGGAACAGTACGGCGACGAGAA GAATCCCCTGTACAAGT

ACTACGAGGAAACCGGGAACTACCTGACCAAGTACTCCAAAAAGGACAACGGCCCCG TGATCAAGAAGATTAAG

TATTACGGCAACAAACTGAACGCCCATCTGGACATCACCGACGACTACCCCAACAGC AGAAACAAGGTCGTGAA

GCTGTCCCTGAAGCCCTACAGATTCGACGTGTACCTGGACAATGGCGTGTACAAGTT CGTGACCGTGAAGAATC

TGGATGTGATCAAAAAAGAAAACTACTACGAAGTGAATAGCAAGTGCTATGAGGAAG CTAAGAAGCTGAAGAAGA

TCAGCAACCAGGCCGAGTTTATCGCCTCCTTCTACAACAACGATCTGATCAAGATCA ACGGCGAGCTGTATAGA

GTGATCGGCGTGAACAACGACCTGCTGAACCGGATCGAAGTGAACATGATCGACATC ACCTACCGCGAGTACCT GGAAAACATGAACGACAAGAGGCCCCCCAGGATCATTAAGACAATCGCCTCCAAGACCCA GAGCATTAAGAAGT

ACAGCACAGACATTCTGGGCAACCTGTATGAAGTGAAATCTAAGAAGCACCCTCAGA TCATCAAAAAGGGCAAAA

GGCCGGCGGCCACGAAAAAGGCCGGCCAGGCAAAAAAGAAAAAGGGATCCGGACGGG CTGACGCATTGGACG

ATTTTGATCTGGATATGCTGGGAAGTGACGCCCTCGATGATTTTGACCTTGACATGC TTGGTTCGGATGCCCTTG

ATGACTTTGACCTCGACATGCTCGGCAGTGACGCCCTTGATGATTTCGACCTGGACA TGCTGATTAACTGTACAG

GCAGTGGAGAGGGCAGAGGAAGTCTGCTAACATGCGGTGACGTCGAGGAGAATCCTG GCCCAATGGCCAAGC

CTTTGTCTCAAGAAGAATCCACCCTCATTGAAAGAGCAACGGCTACAATCAACAGCA TCCCCATCTCTGAAGACT

ACAGCGTCGCCAGCGCAGCTCTCTCTAGCGACGGCCGCATCTTCACTGGTGTCAATG TATATCATTTTACTGGG

GGACCTTGTGCAGAACTCGTGGTGCTGGGCACTGCTGCTGCTGCGGCAGCTGGCAAC CTGACTTGTATCGTCG

CGATCGGAAATGAGAACAGGGGCATCTTGAGCCCCTGCGGACGGTGCCGACAGGTGC TTCTCGATCTGCATCC

TGGGATCAAAGCCATAGTGAAGGACAGTGATGGACAGCCGACGGCAGTTGGGATTCG TGAATTGCTGCCCTCT

GGTTATGTGTGGGAGGGCTAAGAATTCCTAGAGCTCGCTGATCAGCCTCGACTGTGC CTTCTAGTTGCCAGCCA

TCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACT GTCCTTTCCTAATAAAAT

GAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTG GGGCAGGACAGCAAGG

GGGAGGATTGGGAAGAGAATAGCAGGCATGCTGGGGAGGTACCGAGGGCCTATTTCC CATGATTCCTTCATATT

TGCATATACGATACAAGGCTGTTAGAGAGATAATTGGAATTAATTTGACTGTAAACA CAAAGATATTAGTACAAAA

TACGTGACGTAGAAAGTAATAATTTCTTGGGTAGTTTGCAGTTTTAAAATTATGTTT TAAAATGGACTATCATATGC

TTACCGTAACTTGAAAGTATTTCGATTTCTTGGCTTTATATATCTTGTGGAAAGGAC GAAAcaccgTGTATAGCTGC

AGATTGGATAgTTTTAGTACTCTGGAAACAGAATCTACTAAAACAAGGCAAAATGCC GTGTTTATCTCGTCAACTT

GTTGGCGAGATTTTTGCGGCCGCAGGAACCCCTAGTGATGGAGTTGGCCACTCCCTC TCTGCGCGCTCGCTCG

CTCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGGGCTTTGCCCGGGCGGCC TCAGTGAGCGAGCG

AGCGCGCAGCTGCCTGCAGGGGCGCCTGATGCGGTATTTTCTCCTTACGCATCTGTG CGGTATTTCACACCGCA

TACGTCAAAGCAACCATAGTACGCGCCCTGTAGCGGCGCATTAAGCGCGGCGGGTGT GGTGGTTACGCGCAGC

GTGACCGCTACACTTGCCAGCGCCTTAGCGCCCGCTCCTTTCGCTTTCTTCCCTTCC TTTCTCGCCACGTTCGC

CGGCTTTCCCCGTCAAGCTCTAAATCGGGGGCTCCCTTTAGGGTTCCGATTTAGTGC TTTACGGCACCTCGACC

CCAAAAAACTTGATTTGGGTGATGGTTCACGTAGTGGGCCATCGCCCTGATAGACGG TTTTTCGCCCTTTGACGT

TGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAACTGGAACAACACTCAACT CTATCTCGGGCTATTCTTT

TGATTTATAAGGGATTTTGCCGATTTCGGTCTATTGGTTAAAAAATGAGCTGATTTA ACAAAAATTTAACGCGAATT

TTAACAAAATATTAACGTTTACAATTTTATGGTGCACTCTCAGTACAATCTGCTCTG ATGCCGCATAGTTAAGCCA

GCCCCGACACCCGCCAACACCCGCTGACGCGCCCTGACGGGCTTGTCTGCTCCCGGC ATCCGCTTACAGACAA

GCTGTGACCGTCTCCGGGAGCTGCATGTGTCAGAGGTTTTCACCGTCATCACCGAAA CGCGCGAGACGAAAGG

GCCTCGTGATACGCCTATTTTTATAGGTTAATGTCATGATAATAATGGTTTCTTAGA CGTCAGGTGGCACTTTTCG

GGGAAATGTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTA TCCGCTCATGAGACAATAA

CCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTC CGTGTCGCCCTTATTCCCT

TTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAA AAGATGCTGAAGATCAGTT

GGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAG TTTTCGCCCCGAAGAAC

GTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTA TTGACGCCGGGCAAGAGC

AACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCA CAGAAAAGCATCTTACGG

ATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTG CGGCCAACTTACTTCTGA

CAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATG TAACTCGCCTTGATCGT

TGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCT GTAGCAATGGCAACAA

CGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAA TAGACTGGATGGAGGCG

GATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCT GATAAATCTGGAGCCGG

TGAGCGTGGAAGCCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCG TATCGTAGTTATCTACA

CGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTG CCTCACTGATTAAGCAT

TGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCAT TTTTAATTTAAAAGGATCTAG

GTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTC CACTGAGCGTCAGACCCC

GTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGC TTGCAAACAAAAAAACCAC

CGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGG TAACTGGCTTCAGCAGA

GCGCAGATACCAAATACTGTTCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAG AACTCTGTAGCACCGCCT

ACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCG TGTCTTACCGGGTTGGA

CTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTG CACACAGCCCAGCTTG

GAGCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCC ACGCTTCCCGAAGGGA GAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGGAGC TTCCAGGGGGA

AACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGA TTTTTGTGATGCTCGTCA

GGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCC TTTTGCTGGCCTTTTG

CTCACATGT

1.8 GABRA2

Nucleotide sequence of sasgRNA for mouse GABRA2; sgRNA1 (SEQ ID NO: 99)

GGGAGTAGCGATCGCAGGAGC

Nucleotide sequence of sasgRNA for mouse GABRA2; sgRNA2 (SEQ ID NO: 100)

AGGGAGTAGCGATCGCAGGAG

Nucleotide sequence of sasgRNA for mouse GABRA2; sgRNA3 (SEQ ID NO: 101)

TAGCGATCGCAGGAGCCGGGG pAAV-CMV-sadCas9-U6gRNA(Gabra2-sa sgRNA1) used in in vitro qPCR experiments (SEQ ID NO: 102)

CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCGTCGGGCGACC TTTGGTCGCCCGGCC

TCAGTGAGCGAGCGAGCGCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCC TGCGGCCTCTAGACTC

GAGGCGTTGACATTGATTATTGACTAGTTATTAATAGTAATCAATTACGGGGTCATT AGTTCATAGCCCATATATG

GAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGAC CCCCGCCCATTGACGT

CAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAAT GGGTGGAGTATTTACGGT

AAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTG ACGTCAATGACGGTAAAT

GGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGT ACATCTACGTATTAGTCA

TCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAATGGGCGTGGATAGCGGT TTGACTCACGGGGATTT

CCAAGTCTCCACCCCATTGACGTCAATGGGAGTTTGTTTTGGCACCAAAATCAACGG GACTTTCCAAAATGTCGT

AACAACTCCGCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTAT ATAAGCAGAGCTCTCT

GGCTAACTACCGGTGCCACCATGGCCCCAAAGAAGAAGCGGAAGGTCGGTATCCACG GAGTCCCAGCAGCCAA

GCGGAACTACATCCTGGGCCTGGCCATCGGCATCACCAGCGTGGGCTACGGCATCAT CGACTACGAGACACGG

GACGTGATCGATGCCGGCGTGCGGCTGTTCAAAGAGGCCAACGTGGAAAACAACGAG GGCAGGCGGAGCAAG

AGAGGCGCCAGAAGGCTGAAGCGGCGGAGGCGGCATAGAATCCAGAGAGTGAAGAAG CTGCTGTTCGACTAC

AACCTGCTGACCGACCACAGCGAGCTGAGCGGCATCAACCCCTACGAGGCCAGAGTG AAGGGCCTGAGCCAG

AAGCTGAGCGAGGAAGAGTTCTCTGCCGCCCTGCTGCACCTGGCCAAGAGAAGAGGC GTGCACAACGTGAACG

AGGTGGAAGAGGACACCGGCAACGAGCTGTCCACCAAAGAGCAGATCAGCCGGAACA GCAAGGCCCTGGAAG

AGAAATACGTGGCCGAACTGCAGCTGGAACGGCTGAAGAAAGACGGCGAAGTGCGGG GCAGCATCAACAGATT

CAAGACCAGCGACTACGTGAAAGAAGCCAAACAGCTGCTGAAGGTGCAGAAGGCCTA CCACCAGCTGGACCAG

AGCTTCATCGACACCTACATCGACCTGCTGGAAACCCGGCGGACCTACTATGAGGGA CCTGGCGAGGGCAGCC

CCTTCGGCTGGAAGGACATCAAAGAATGGTACGAGATGCTGATGGGCCACTGCACCT ACTTCCCCGAGGAACT

GCGGAGCGTGAAGTACGCCTACAACGCCGACCTGTACAACGCCCTGAACGACCTGAA CAATCTCGTGATCACC

AGGGACGAGAACGAGAAGCTGGAATATTACGAGAAGTTCCAGATCATCGAGAACGTG TTCAAGCAGAAGAAGAA

GCCCACCCTGAAGCAGATCGCCAAAGAAATCCTCGTGAACGAAGAGGATATTAAGGG CTACAGAGTGACCAGCA

CCGGCAAGCCCGAGTTCACCAACCTGAAGGTGTACCACGACATCAAGGACATTACCG CCCGGAAAGAGATTATT

GAGAACGCCGAGCTGCTGGATCAGATTGCCAAGATCCTGACCATCTACCAGAGCAGC GAGGACATCCAGGAAG

AACTGACCAATCTGAACTCCGAGCTGACCCAGGAAGAGATCGAGCAGATCTCTAATC TGAAGGGCTATACCGGC

ACCCACAACCTGAGCCTGAAGGCCATCAACCTGATCCTGGACGAGCTGTGGCACACC AACGACAACCAGATCG

CTATCTTCAACCGGCTGAAGCTGGTGCCCAAGAAGGTGGACCTGTCCCAGCAGAAAG AGATCCCCACCACCCT

GGTGGACGACTTCATCCTGAGCCCCGTCGTGAAGAGAAGCTTCATCCAGAGCATCAA AGTGATCAACGCCATCA

TCAAGAAGTACGGCCTGCCCAACGACATCATTATCGAGCTGGCCCGCGAGAAGAACT CCAAGGACGCCCAGAA

AATGATCAACGAGATGCAGAAGCGGAACCGGCAGACCAACGAGCGGATCGAGGAAAT CATCCGGACCACCGGC

AAAGAGAACGCCAAGTACCTGATCGAGAAGATCAAGCTGCACGACATGCAGGAAGGC AAGTGCCTGTACAGCC

TGGAAGCCATCCCTCTGGAAGATCTGCTGAACAACCCCTTCAACTATGAGGTGGACC ACATCATCCCCAGAAGC

GTGTCCTTCGACAACAGCTTCAACAACAAGGTGCTCGTGAAGCAGGAAGAAGCCAGC AAGAAGGGCAACCGGA CCCCATTCCAGTACCTGAGCAGCAGCGACAGCAAGATCAGCTACGAAACCTTCAAGAAGC ACATCCTGAATCTG

GCCAAGGGCAAGGGCAGAATCAGCAAGACCAAGAAAGAGTATCTGCTGGAAGAACGG GACATCAACAGGTTCT

CCGTGCAGAAAGACTTCATCAACCGGAACCTGGTGGATACCAGATACGCCACCAGAG GCCTGATGAACCTGCT

GCGGAGCTACTTCAGAGTGAACAACCTGGACGTGAAAGTGAAGTCCATCAATGGCGG CTTCACCAGCTTTCTGC

GGCGGAAGTGGAAGTTTAAGAAAGAGCGGAACAAGGGGTACAAGCACCACGCCGAGG ACGCCCTGATCATTGC

CAACGCCGATTTCATCTTCAAAGAGTGGAAGAAACTGGACAAGGCCAAAAAAGTGAT GGAAAACCAGATGTTCG

AGGAAAAGCAGGCCGAGAGCATGCCCGAGATCGAAACCGAGCAGGAGTACAAAGAGA TCTTCATCACCCCCCA

CCAGATCAAGCACATTAAGGACTTCAAGGACTACAAGTACAGCCACCGGGTGGACAA GAAGCCTAATAGAGAGC

TGATTAACGACACCCTGTACTCCACCCGGAAGGACGACAAGGGCAACACCCTGATCG TGAACAATCTGAACGGC

CTGTACGACAAGGACAATGACAAGCTGAAAAAGCTGATCAACAAGAGCCCCGAAAAG CTGCTGATGTACCACCA

CGACCCCCAGACCTACCAGAAACTGAAGCTGATTATGGAACAGTACGGCGACGAGAA GAATCCCCTGTACAAGT

ACTACGAGGAAACCGGGAACTACCTGACCAAGTACTCCAAAAAGGACAACGGCCCCG TGATCAAGAAGATTAAG

TATTACGGCAACAAACTGAACGCCCATCTGGACATCACCGACGACTACCCCAACAGC AGAAACAAGGTCGTGAA

GCTGTCCCTGAAGCCCTACAGATTCGACGTGTACCTGGACAATGGCGTGTACAAGTT CGTGACCGTGAAGAATC

TGGATGTGATCAAAAAAGAAAACTACTACGAAGTGAATAGCAAGTGCTATGAGGAAG CTAAGAAGCTGAAGAAGA

TCAGCAACCAGGCCGAGTTTATCGCCTCCTTCTACAACAACGATCTGATCAAGATCA ACGGCGAGCTGTATAGA

GTGATCGGCGTGAACAACGACCTGCTGAACCGGATCGAAGTGAACATGATCGACATC ACCTACCGCGAGTACCT

GGAAAACATGAACGACAAGAGGCCCCCCAGGATCATTAAGACAATCGCCTCCAAGAC CCAGAGCATTAAGAAGT

ACAGCACAGACATTCTGGGCAACCTGTATGAAGTGAAATCTAAGAAGCACCCTCAGA TCATCAAAAAGGGCAAAA

GGCCGGCGGCCACGAAAAAGGCCGGCCAGGCAAAAAAGAAAAAGGGATCCGGACGGG CTGACGCATTGGACG

ATTTTGATCTGGATATGCTGGGAAGTGACGCCCTCGATGATTTTGACCTTGACATGC TTGGTTCGGATGCCCTTG

ATGACTTTGACCTCGACATGCTCGGCAGTGACGCCCTTGATGATTTCGACCTGGACA TGCTGATTAACTGTACAG

GCAGTGGAGAGGGCAGAGGAAGTCTGCTAACATGCGGTGACGTCGAGGAGAATCCTG GCCCAATGGCCAAGC

CTTTGTCTCAAGAAGAATCCACCCTCATTGAAAGAGCAACGGCTACAATCAACAGCA TCCCCATCTCTGAAGACT

ACAGCGTCGCCAGCGCAGCTCTCTCTAGCGACGGCCGCATCTTCACTGGTGTCAATG TATATCATTTTACTGGG

GGACCTTGTGCAGAACTCGTGGTGCTGGGCACTGCTGCTGCTGCGGCAGCTGGCAAC CTGACTTGTATCGTCG

CGATCGGAAATGAGAACAGGGGCATCTTGAGCCCCTGCGGACGGTGCCGACAGGTGC TTCTCGATCTGCATCC

TGGGATCAAAGCCATAGTGAAGGACAGTGATGGACAGCCGACGGCAGTTGGGATTCG TGAATTGCTGCCCTCT

GGTTATGTGTGGGAGGGCTAAGAATTCCTAGAGCTCGCTGATCAGCCTCGACTGTGC CTTCTAGTTGCCAGCCA

TCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACT GTCCTTTCCTAATAAAAT

GAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTG GGGCAGGACAGCAAGG

GGGAGGATTGGGAAGAGAATAGCAGGCATGCTGGGGAGGTACCGAGGGCCTATTTCC CATGATTCCTTCATATT

TGCATATACGATACAAGGCTGTTAGAGAGATAATTGGAATTAATTTGACTGTAAACA CAAAGATATTAGTACAAAA

TACGTGACGTAGAAAGTAATAATTTCTTGGGTAGTTTGCAGTTTTAAAATTATGTTT TAAAATGGACTATCATATGC

TTACCGTAACTTGAAAGTATTTCGATTTCTTGGCTTTATATATCTTGTGGAAAGGAC GAAAcaccGGGAGTAGCGAT

CGCAGGAGCgTTTTAGTACTCTGGAAACAGAATCTACTAAAACAAGGCAAAATGCCG TGTTTATCTCGTCAACTT

GTTGGCGAGATTTTTGCGGCCGCAGGAACCCCTAGTGATGGAGTTGGCCACTCCCTC TCTGCGCGCTCGCTCG

CTCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGGGCTTTGCCCGGGCGGCC TCAGTGAGCGAGCG

AGCGCGCAGCTGCCTGCAGGGGCGCCTGATGCGGTATTTTCTCCTTACGCATCTGTG CGGTATTTCACACCGCA

TACGTCAAAGCAACCATAGTACGCGCCCTGTAGCGGCGCATTAAGCGCGGCGGGTGT GGTGGTTACGCGCAGC

GTGACCGCTACACTTGCCAGCGCCTTAGCGCCCGCTCCTTTCGCTTTCTTCCCTTCC TTTCTCGCCACGTTCGC

CGGCTTTCCCCGTCAAGCTCTAAATCGGGGGCTCCCTTTAGGGTTCCGATTTAGTGC TTTACGGCACCTCGACC

CCAAAAAACTTGATTTGGGTGATGGTTCACGTAGTGGGCCATCGCCCTGATAGACGG TTTTTCGCCCTTTGACGT

TGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAACTGGAACAACACTCAACT CTATCTCGGGCTATTCTTT

TGATTTATAAGGGATTTTGCCGATTTCGGTCTATTGGTTAAAAAATGAGCTGATTTA ACAAAAATTTAACGCGAATT

TTAACAAAATATTAACGTTTACAATTTTATGGTGCACTCTCAGTACAATCTGCTCTG ATGCCGCATAGTTAAGCCA

GCCCCGACACCCGCCAACACCCGCTGACGCGCCCTGACGGGCTTGTCTGCTCCCGGC ATCCGCTTACAGACAA

GCTGTGACCGTCTCCGGGAGCTGCATGTGTCAGAGGTTTTCACCGTCATCACCGAAA CGCGCGAGACGAAAGG

GCCTCGTGATACGCCTATTTTTATAGGTTAATGTCATGATAATAATGGTTTCTTAGA CGTCAGGTGGCACTTTTCG

GGGAAATGTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTA TCCGCTCATGAGACAATAA

CCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTC CGTGTCGCCCTTATTCCCT

TTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAA AAGATGCTGAAGATCAGTT

GGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAG TTTTCGCCCCGAAGAAC GTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTATTG ACGCCGGGCAAGAGC

AACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCA CAGAAAAGCATCTTACGG

ATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTG CGGCCAACTTACTTCTGA

CAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATG TAACTCGCCTTGATCGT

TGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCT GTAGCAATGGCAACAA

CGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAA TAGACTGGATGGAGGCG

GATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCT GATAAATCTGGAGCCGG

TGAGCGTGGAAGCCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCG TATCGTAGTTATCTACA

CGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTG CCTCACTGATTAAGCAT

TGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCAT TTTTAATTTAAAAGGATCTAG

GTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTC CACTGAGCGTCAGACCCC

GTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGC TTGCAAACAAAAAAACCAC

CGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGG TAACTGGCTTCAGCAGA

GCGCAGATACCAAATACTGTTCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAG AACTCTGTAGCACCGCCT

ACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCG TGTCTTACCGGGTTGGA

CTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTG CACACAGCCCAGCTTG

GAGCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCC ACGCTTCCCGAAGGGA

GAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGG AGCTTCCAGGGGGA

AACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGA TTTTTGTGATGCTCGTCA

GGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCC TTTTGCTGGCCTTTTG

CTCACATGT pAAV-CMV-sadCas9-U6gRNA(Gabra2-sa sgRNA2) used in in vitro qPCR experiments (SEQ ID NO: 103)

CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCGTCGGGCGACC TTTGGTCGCCCGGCC

TCAGTGAGCGAGCGAGCGCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCC TGCGGCCTCTAGACTC

GAGGCGTTGACATTGATTATTGACTAGTTATTAATAGTAATCAATTACGGGGTCATT AGTTCATAGCCCATATATG

GAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGAC CCCCGCCCATTGACGT

CAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAAT GGGTGGAGTATTTACGGT

AAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTG ACGTCAATGACGGTAAAT

GGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGT ACATCTACGTATTAGTCA

TCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAATGGGCGTGGATAGCGGT TTGACTCACGGGGATTT

CCAAGTCTCCACCCCATTGACGTCAATGGGAGTTTGTTTTGGCACCAAAATCAACGG GACTTTCCAAAATGTCGT

AACAACTCCGCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTAT ATAAGCAGAGCTCTCT

GGCTAACTACCGGTGCCACCATGGCCCCAAAGAAGAAGCGGAAGGTCGGTATCCACG GAGTCCCAGCAGCCAA

GCGGAACTACATCCTGGGCCTGGCCATCGGCATCACCAGCGTGGGCTACGGCATCAT CGACTACGAGACACGG

GACGTGATCGATGCCGGCGTGCGGCTGTTCAAAGAGGCCAACGTGGAAAACAACGAG GGCAGGCGGAGCAAG

AGAGGCGCCAGAAGGCTGAAGCGGCGGAGGCGGCATAGAATCCAGAGAGTGAAGAAG CTGCTGTTCGACTAC

AACCTGCTGACCGACCACAGCGAGCTGAGCGGCATCAACCCCTACGAGGCCAGAGTG AAGGGCCTGAGCCAG

AAGCTGAGCGAGGAAGAGTTCTCTGCCGCCCTGCTGCACCTGGCCAAGAGAAGAGGC GTGCACAACGTGAACG

AGGTGGAAGAGGACACCGGCAACGAGCTGTCCACCAAAGAGCAGATCAGCCGGAACA GCAAGGCCCTGGAAG

AGAAATACGTGGCCGAACTGCAGCTGGAACGGCTGAAGAAAGACGGCGAAGTGCGGG GCAGCATCAACAGATT

CAAGACCAGCGACTACGTGAAAGAAGCCAAACAGCTGCTGAAGGTGCAGAAGGCCTA CCACCAGCTGGACCAG

AGCTTCATCGACACCTACATCGACCTGCTGGAAACCCGGCGGACCTACTATGAGGGA CCTGGCGAGGGCAGCC

CCTTCGGCTGGAAGGACATCAAAGAATGGTACGAGATGCTGATGGGCCACTGCACCT ACTTCCCCGAGGAACT

GCGGAGCGTGAAGTACGCCTACAACGCCGACCTGTACAACGCCCTGAACGACCTGAA CAATCTCGTGATCACC

AGGGACGAGAACGAGAAGCTGGAATATTACGAGAAGTTCCAGATCATCGAGAACGTG TTCAAGCAGAAGAAGAA

GCCCACCCTGAAGCAGATCGCCAAAGAAATCCTCGTGAACGAAGAGGATATTAAGGG CTACAGAGTGACCAGCA

CCGGCAAGCCCGAGTTCACCAACCTGAAGGTGTACCACGACATCAAGGACATTACCG CCCGGAAAGAGATTATT

GAGAACGCCGAGCTGCTGGATCAGATTGCCAAGATCCTGACCATCTACCAGAGCAGC GAGGACATCCAGGAAG

AACTGACCAATCTGAACTCCGAGCTGACCCAGGAAGAGATCGAGCAGATCTCTAATC TGAAGGGCTATACCGGC

ACCCACAACCTGAGCCTGAAGGCCATCAACCTGATCCTGGACGAGCTGTGGCACACC AACGACAACCAGATCG

CTATCTTCAACCGGCTGAAGCTGGTGCCCAAGAAGGTGGACCTGTCCCAGCAGAAAG AGATCCCCACCACCCT

GGTGGACGACTTCATCCTGAGCCCCGTCGTGAAGAGAAGCTTCATCCAGAGCATCAA AGTGATCAACGCCATCA TCAAGAAGTACGGCCTGCCCAACGACATCATTATCGAGCTGGCCCGCGAGAAGAACTCCA AGGACGCCCAGAA

AATGATCAACGAGATGCAGAAGCGGAACCGGCAGACCAACGAGCGGATCGAGGAAAT CATCCGGACCACCGGC

AAAGAGAACGCCAAGTACCTGATCGAGAAGATCAAGCTGCACGACATGCAGGAAGGC AAGTGCCTGTACAGCC

TGGAAGCCATCCCTCTGGAAGATCTGCTGAACAACCCCTTCAACTATGAGGTGGACC ACATCATCCCCAGAAGC

GTGTCCTTCGACAACAGCTTCAACAACAAGGTGCTCGTGAAGCAGGAAGAAGCCAGC AAGAAGGGCAACCGGA

CCCCATTCCAGTACCTGAGCAGCAGCGACAGCAAGATCAGCTACGAAACCTTCAAGA AGCACATCCTGAATCTG

GCCAAGGGCAAGGGCAGAATCAGCAAGACCAAGAAAGAGTATCTGCTGGAAGAACGG GACATCAACAGGTTCT

CCGTGCAGAAAGACTTCATCAACCGGAACCTGGTGGATACCAGATACGCCACCAGAG GCCTGATGAACCTGCT

GCGGAGCTACTTCAGAGTGAACAACCTGGACGTGAAAGTGAAGTCCATCAATGGCGG CTTCACCAGCTTTCTGC

GGCGGAAGTGGAAGTTTAAGAAAGAGCGGAACAAGGGGTACAAGCACCACGCCGAGG ACGCCCTGATCATTGC

CAACGCCGATTTCATCTTCAAAGAGTGGAAGAAACTGGACAAGGCCAAAAAAGTGAT GGAAAACCAGATGTTCG

AGGAAAAGCAGGCCGAGAGCATGCCCGAGATCGAAACCGAGCAGGAGTACAAAGAGA TCTTCATCACCCCCCA

CCAGATCAAGCACATTAAGGACTTCAAGGACTACAAGTACAGCCACCGGGTGGACAA GAAGCCTAATAGAGAGC

TGATTAACGACACCCTGTACTCCACCCGGAAGGACGACAAGGGCAACACCCTGATCG TGAACAATCTGAACGGC

CTGTACGACAAGGACAATGACAAGCTGAAAAAGCTGATCAACAAGAGCCCCGAAAAG CTGCTGATGTACCACCA

CGACCCCCAGACCTACCAGAAACTGAAGCTGATTATGGAACAGTACGGCGACGAGAA GAATCCCCTGTACAAGT

ACTACGAGGAAACCGGGAACTACCTGACCAAGTACTCCAAAAAGGACAACGGCCCCG TGATCAAGAAGATTAAG

TATTACGGCAACAAACTGAACGCCCATCTGGACATCACCGACGACTACCCCAACAGC AGAAACAAGGTCGTGAA

GCTGTCCCTGAAGCCCTACAGATTCGACGTGTACCTGGACAATGGCGTGTACAAGTT CGTGACCGTGAAGAATC

TGGATGTGATCAAAAAAGAAAACTACTACGAAGTGAATAGCAAGTGCTATGAGGAAG CTAAGAAGCTGAAGAAGA

TCAGCAACCAGGCCGAGTTTATCGCCTCCTTCTACAACAACGATCTGATCAAGATCA ACGGCGAGCTGTATAGA

GTGATCGGCGTGAACAACGACCTGCTGAACCGGATCGAAGTGAACATGATCGACATC ACCTACCGCGAGTACCT

GGAAAACATGAACGACAAGAGGCCCCCCAGGATCATTAAGACAATCGCCTCCAAGAC CCAGAGCATTAAGAAGT

ACAGCACAGACATTCTGGGCAACCTGTATGAAGTGAAATCTAAGAAGCACCCTCAGA TCATCAAAAAGGGCAAAA

GGCCGGCGGCCACGAAAAAGGCCGGCCAGGCAAAAAAGAAAAAGGGATCCGGACGGG CTGACGCATTGGACG

ATTTTGATCTGGATATGCTGGGAAGTGACGCCCTCGATGATTTTGACCTTGACATGC TTGGTTCGGATGCCCTTG

ATGACTTTGACCTCGACATGCTCGGCAGTGACGCCCTTGATGATTTCGACCTGGACA TGCTGATTAACTGTACAG

GCAGTGGAGAGGGCAGAGGAAGTCTGCTAACATGCGGTGACGTCGAGGAGAATCCTG GCCCAATGGCCAAGC

CTTTGTCTCAAGAAGAATCCACCCTCATTGAAAGAGCAACGGCTACAATCAACAGCA TCCCCATCTCTGAAGACT

ACAGCGTCGCCAGCGCAGCTCTCTCTAGCGACGGCCGCATCTTCACTGGTGTCAATG TATATCATTTTACTGGG

GGACCTTGTGCAGAACTCGTGGTGCTGGGCACTGCTGCTGCTGCGGCAGCTGGCAAC CTGACTTGTATCGTCG

CGATCGGAAATGAGAACAGGGGCATCTTGAGCCCCTGCGGACGGTGCCGACAGGTGC TTCTCGATCTGCATCC

TGGGATCAAAGCCATAGTGAAGGACAGTGATGGACAGCCGACGGCAGTTGGGATTCG TGAATTGCTGCCCTCT

GGTTATGTGTGGGAGGGCTAAGAATTCCTAGAGCTCGCTGATCAGCCTCGACTGTGC CTTCTAGTTGCCAGCCA

TCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACT GTCCTTTCCTAATAAAAT

GAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTG GGGCAGGACAGCAAGG

GGGAGGATTGGGAAGAGAATAGCAGGCATGCTGGGGAGGTACCGAGGGCCTATTTCC CATGATTCCTTCATATT

TGCATATACGATACAAGGCTGTTAGAGAGATAATTGGAATTAATTTGACTGTAAACA CAAAGATATTAGTACAAAA

TACGTGACGTAGAAAGTAATAATTTCTTGGGTAGTTTGCAGTTTTAAAATTATGTTT TAAAATGGACTATCATATGC

TTACCGTAACTTGAAAGTATTTCGATTTCTTGGCTTTATATATCTTGTGGAAAGGAC GAAAcaccgAGGGAGTAGCG

ATCGCAGGAGgTTTTAGTACTCTGGAAACAGAATCTACTAAAACAAGGCAAAATGCC GTGTTTATCTCGTCAACTT

GTTGGCGAGATTTTTGCGGCCGCAGGAACCCCTAGTGATGGAGTTGGCCACTCCCTC TCTGCGCGCTCGCTCG

CTCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGGGCTTTGCCCGGGCGGCC TCAGTGAGCGAGCG

AGCGCGCAGCTGCCTGCAGGGGCGCCTGATGCGGTATTTTCTCCTTACGCATCTGTG CGGTATTTCACACCGCA

TACGTCAAAGCAACCATAGTACGCGCCCTGTAGCGGCGCATTAAGCGCGGCGGGTGT GGTGGTTACGCGCAGC

GTGACCGCTACACTTGCCAGCGCCTTAGCGCCCGCTCCTTTCGCTTTCTTCCCTTCC TTTCTCGCCACGTTCGC

CGGCTTTCCCCGTCAAGCTCTAAATCGGGGGCTCCCTTTAGGGTTCCGATTTAGTGC TTTACGGCACCTCGACC

CCAAAAAACTTGATTTGGGTGATGGTTCACGTAGTGGGCCATCGCCCTGATAGACGG TTTTTCGCCCTTTGACGT

TGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAACTGGAACAACACTCAACT CTATCTCGGGCTATTCTTT

TGATTTATAAGGGATTTTGCCGATTTCGGTCTATTGGTTAAAAAATGAGCTGATTTA ACAAAAATTTAACGCGAATT

TTAACAAAATATTAACGTTTACAATTTTATGGTGCACTCTCAGTACAATCTGCTCTG ATGCCGCATAGTTAAGCCA

GCCCCGACACCCGCCAACACCCGCTGACGCGCCCTGACGGGCTTGTCTGCTCCCGGC ATCCGCTTACAGACAA

GCTGTGACCGTCTCCGGGAGCTGCATGTGTCAGAGGTTTTCACCGTCATCACCGAAA CGCGCGAGACGAAAGG GCCTCGTGATACGCCTATTTTTATAGGTTAATGTCATGATAATAATGGTTTCTTAGACGT CAGGTGGCACTTTTCG

GGGAAATGTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTA TCCGCTCATGAGACAATAA

CCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTC CGTGTCGCCCTTATTCCCT

TTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAA AAGATGCTGAAGATCAGTT

GGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAG TTTTCGCCCCGAAGAAC

GTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTA TTGACGCCGGGCAAGAGC

AACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCA CAGAAAAGCATCTTACGG

ATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTG CGGCCAACTTACTTCTGA

CAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATG TAACTCGCCTTGATCGT

TGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCT GTAGCAATGGCAACAA

CGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAA TAGACTGGATGGAGGCG

GATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCT GATAAATCTGGAGCCGG

TGAGCGTGGAAGCCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCG TATCGTAGTTATCTACA

CGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTG CCTCACTGATTAAGCAT

TGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCAT TTTTAATTTAAAAGGATCTAG

GTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTC CACTGAGCGTCAGACCCC

GTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGC TTGCAAACAAAAAAACCAC

CGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGG TAACTGGCTTCAGCAGA

GCGCAGATACCAAATACTGTTCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAG AACTCTGTAGCACCGCCT

ACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCG TGTCTTACCGGGTTGGA

CTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTG CACACAGCCCAGCTTG

GAGCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCC ACGCTTCCCGAAGGGA

GAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGG AGCTTCCAGGGGGA

AACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGA TTTTTGTGATGCTCGTCA

GGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCC TTTTGCTGGCCTTTTG

CTCACATGT pAAV-CMV-sadCas9-U6gRNA(Gabra2-sa sgRNA3) used in in vitro qPCR experiments (SEQ ID NO: 104)

CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCGTCGGGCGACC TTTGGTCGCCCGGCC

TCAGTGAGCGAGCGAGCGCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCC TGCGGCCTCTAGACTC

GAGGCGTTGACATTGATTATTGACTAGTTATTAATAGTAATCAATTACGGGGTCATT AGTTCATAGCCCATATATG

GAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGAC CCCCGCCCATTGACGT

CAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAAT GGGTGGAGTATTTACGGT

AAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTG ACGTCAATGACGGTAAAT

GGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGT ACATCTACGTATTAGTCA

TCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAATGGGCGTGGATAGCGGT TTGACTCACGGGGATTT

CCAAGTCTCCACCCCATTGACGTCAATGGGAGTTTGTTTTGGCACCAAAATCAACGG GACTTTCCAAAATGTCGT

AACAACTCCGCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTAT ATAAGCAGAGCTCTCT

GGCTAACTACCGGTGCCACCATGGCCCCAAAGAAGAAGCGGAAGGTCGGTATCCACG GAGTCCCAGCAGCCAA

GCGGAACTACATCCTGGGCCTGGCCATCGGCATCACCAGCGTGGGCTACGGCATCAT CGACTACGAGACACGG

GACGTGATCGATGCCGGCGTGCGGCTGTTCAAAGAGGCCAACGTGGAAAACAACGAG GGCAGGCGGAGCAAG

AGAGGCGCCAGAAGGCTGAAGCGGCGGAGGCGGCATAGAATCCAGAGAGTGAAGAAG CTGCTGTTCGACTAC

AACCTGCTGACCGACCACAGCGAGCTGAGCGGCATCAACCCCTACGAGGCCAGAGTG AAGGGCCTGAGCCAG

AAGCTGAGCGAGGAAGAGTTCTCTGCCGCCCTGCTGCACCTGGCCAAGAGAAGAGGC GTGCACAACGTGAACG

AGGTGGAAGAGGACACCGGCAACGAGCTGTCCACCAAAGAGCAGATCAGCCGGAACA GCAAGGCCCTGGAAG

AGAAATACGTGGCCGAACTGCAGCTGGAACGGCTGAAGAAAGACGGCGAAGTGCGGG GCAGCATCAACAGATT

CAAGACCAGCGACTACGTGAAAGAAGCCAAACAGCTGCTGAAGGTGCAGAAGGCCTA CCACCAGCTGGACCAG

AGCTTCATCGACACCTACATCGACCTGCTGGAAACCCGGCGGACCTACTATGAGGGA CCTGGCGAGGGCAGCC

CCTTCGGCTGGAAGGACATCAAAGAATGGTACGAGATGCTGATGGGCCACTGCACCT ACTTCCCCGAGGAACT

GCGGAGCGTGAAGTACGCCTACAACGCCGACCTGTACAACGCCCTGAACGACCTGAA CAATCTCGTGATCACC

AGGGACGAGAACGAGAAGCTGGAATATTACGAGAAGTTCCAGATCATCGAGAACGTG TTCAAGCAGAAGAAGAA

GCCCACCCTGAAGCAGATCGCCAAAGAAATCCTCGTGAACGAAGAGGATATTAAGGG CTACAGAGTGACCAGCA

CCGGCAAGCCCGAGTTCACCAACCTGAAGGTGTACCACGACATCAAGGACATTACCG CCCGGAAAGAGATTATT GAGAACGCCGAGCTGCTGGATCAGATTGCCAAGATCCTGACCATCTACCAGAGCAGCGAG GACATCCAGGAAG

AACTGACCAATCTGAACTCCGAGCTGACCCAGGAAGAGATCGAGCAGATCTCTAATC TGAAGGGCTATACCGGC

ACCCACAACCTGAGCCTGAAGGCCATCAACCTGATCCTGGACGAGCTGTGGCACACC AACGACAACCAGATCG

CTATCTTCAACCGGCTGAAGCTGGTGCCCAAGAAGGTGGACCTGTCCCAGCAGAAAG AGATCCCCACCACCCT

GGTGGACGACTTCATCCTGAGCCCCGTCGTGAAGAGAAGCTTCATCCAGAGCATCAA AGTGATCAACGCCATCA

TCAAGAAGTACGGCCTGCCCAACGACATCATTATCGAGCTGGCCCGCGAGAAGAACT CCAAGGACGCCCAGAA

AATGATCAACGAGATGCAGAAGCGGAACCGGCAGACCAACGAGCGGATCGAGGAAAT CATCCGGACCACCGGC

AAAGAGAACGCCAAGTACCTGATCGAGAAGATCAAGCTGCACGACATGCAGGAAGGC AAGTGCCTGTACAGCC

TGGAAGCCATCCCTCTGGAAGATCTGCTGAACAACCCCTTCAACTATGAGGTGGACC ACATCATCCCCAGAAGC

GTGTCCTTCGACAACAGCTTCAACAACAAGGTGCTCGTGAAGCAGGAAGAAGCCAGC AAGAAGGGCAACCGGA

CCCCATTCCAGTACCTGAGCAGCAGCGACAGCAAGATCAGCTACGAAACCTTCAAGA AGCACATCCTGAATCTG

GCCAAGGGCAAGGGCAGAATCAGCAAGACCAAGAAAGAGTATCTGCTGGAAGAACGG GACATCAACAGGTTCT

CCGTGCAGAAAGACTTCATCAACCGGAACCTGGTGGATACCAGATACGCCACCAGAG GCCTGATGAACCTGCT

GCGGAGCTACTTCAGAGTGAACAACCTGGACGTGAAAGTGAAGTCCATCAATGGCGG CTTCACCAGCTTTCTGC

GGCGGAAGTGGAAGTTTAAGAAAGAGCGGAACAAGGGGTACAAGCACCACGCCGAGG ACGCCCTGATCATTGC

CAACGCCGATTTCATCTTCAAAGAGTGGAAGAAACTGGACAAGGCCAAAAAAGTGAT GGAAAACCAGATGTTCG

AGGAAAAGCAGGCCGAGAGCATGCCCGAGATCGAAACCGAGCAGGAGTACAAAGAGA TCTTCATCACCCCCCA

CCAGATCAAGCACATTAAGGACTTCAAGGACTACAAGTACAGCCACCGGGTGGACAA GAAGCCTAATAGAGAGC

TGATTAACGACACCCTGTACTCCACCCGGAAGGACGACAAGGGCAACACCCTGATCG TGAACAATCTGAACGGC

CTGTACGACAAGGACAATGACAAGCTGAAAAAGCTGATCAACAAGAGCCCCGAAAAG CTGCTGATGTACCACCA

CGACCCCCAGACCTACCAGAAACTGAAGCTGATTATGGAACAGTACGGCGACGAGAA GAATCCCCTGTACAAGT

ACTACGAGGAAACCGGGAACTACCTGACCAAGTACTCCAAAAAGGACAACGGCCCCG TGATCAAGAAGATTAAG

TATTACGGCAACAAACTGAACGCCCATCTGGACATCACCGACGACTACCCCAACAGC AGAAACAAGGTCGTGAA

GCTGTCCCTGAAGCCCTACAGATTCGACGTGTACCTGGACAATGGCGTGTACAAGTT CGTGACCGTGAAGAATC

TGGATGTGATCAAAAAAGAAAACTACTACGAAGTGAATAGCAAGTGCTATGAGGAAG CTAAGAAGCTGAAGAAGA

TCAGCAACCAGGCCGAGTTTATCGCCTCCTTCTACAACAACGATCTGATCAAGATCA ACGGCGAGCTGTATAGA

GTGATCGGCGTGAACAACGACCTGCTGAACCGGATCGAAGTGAACATGATCGACATC ACCTACCGCGAGTACCT

GGAAAACATGAACGACAAGAGGCCCCCCAGGATCATTAAGACAATCGCCTCCAAGAC CCAGAGCATTAAGAAGT

ACAGCACAGACATTCTGGGCAACCTGTATGAAGTGAAATCTAAGAAGCACCCTCAGA TCATCAAAAAGGGCAAAA

GGCCGGCGGCCACGAAAAAGGCCGGCCAGGCAAAAAAGAAAAAGGGATCCGGACGGG CTGACGCATTGGACG

ATTTTGATCTGGATATGCTGGGAAGTGACGCCCTCGATGATTTTGACCTTGACATGC TTGGTTCGGATGCCCTTG

ATGACTTTGACCTCGACATGCTCGGCAGTGACGCCCTTGATGATTTCGACCTGGACA TGCTGATTAACTGTACAG

GCAGTGGAGAGGGCAGAGGAAGTCTGCTAACATGCGGTGACGTCGAGGAGAATCCTG GCCCAATGGCCAAGC

CTTTGTCTCAAGAAGAATCCACCCTCATTGAAAGAGCAACGGCTACAATCAACAGCA TCCCCATCTCTGAAGACT

ACAGCGTCGCCAGCGCAGCTCTCTCTAGCGACGGCCGCATCTTCACTGGTGTCAATG TATATCATTTTACTGGG

GGACCTTGTGCAGAACTCGTGGTGCTGGGCACTGCTGCTGCTGCGGCAGCTGGCAAC CTGACTTGTATCGTCG

CGATCGGAAATGAGAACAGGGGCATCTTGAGCCCCTGCGGACGGTGCCGACAGGTGC TTCTCGATCTGCATCC

TGGGATCAAAGCCATAGTGAAGGACAGTGATGGACAGCCGACGGCAGTTGGGATTCG TGAATTGCTGCCCTCT

GGTTATGTGTGGGAGGGCTAAGAATTCCTAGAGCTCGCTGATCAGCCTCGACTGTGC CTTCTAGTTGCCAGCCA

TCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACT GTCCTTTCCTAATAAAAT

GAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTG GGGCAGGACAGCAAGG

GGGAGGATTGGGAAGAGAATAGCAGGCATGCTGGGGAGGTACCGAGGGCCTATTTCC CATGATTCCTTCATATT

TGCATATACGATACAAGGCTGTTAGAGAGATAATTGGAATTAATTTGACTGTAAACA CAAAGATATTAGTACAAAA

TACGTGACGTAGAAAGTAATAATTTCTTGGGTAGTTTGCAGTTTTAAAATTATGTTT TAAAATGGACTATCATATGC

TTACCGTAACTTGAAAGTATTTCGATTTCTTGGCTTTATATATCTTGTGGAAAGGAC GAAAcaccgTAGCGATCGCA

GGAGCCGGGGgTTTTAGTACTCTGGAAACAGAATCTACTAAAACAAGGCAAAATGCC GTGTTTATCTCGTCAACT

TGTTGGCGAGATTTTTGCGGCCGCAGGAACCCCTAGTGATGGAGTTGGCCACTCCCT CTCTGCGCGCTCGCTC

GCTCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGGGCTTTGCCCGGGCGGC CTCAGTGAGCGAGC

GAGCGCGCAGCTGCCTGCAGGGGCGCCTGATGCGGTATTTTCTCCTTACGCATCTGT GCGGTATTTCACACCG

CATACGTCAAAGCAACCATAGTACGCGCCCTGTAGCGGCGCATTAAGCGCGGCGGGT GTGGTGGTTACGCGCA

GCGTGACCGCTACACTTGCCAGCGCCTTAGCGCCCGCTCCTTTCGCTTTCTTCCCTT CCTTTCTCGCCACGTTC

GCCGGCTTTCCCCGTCAAGCTCTAAATCGGGGGCTCCCTTTAGGGTTCCGATTTAGT GCTTTACGGCACCTCGA

CCCCAAAAAACTTGATTTGGGTGATGGTTCACGTAGTGGGCCATCGCCCTGATAGAC GGTTTTTCGCCCTTTGAC GTTGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAACTGGAACAACACTCAACTC TATCTCGGGCTATTCT

TTTGATTTATAAGGGATTTTGCCGATTTCGGTCTATTGGTTAAAAAATGAGCTGATT TAACAAAAATTTAACGCGAA

TTTTAACAAAATATTAACGTTTACAATTTTATGGTGCACTCTCAGTACAATCTGCTC TGATGCCGCATAGTTAAGCC

AGCCCCGACACCCGCCAACACCCGCTGACGCGCCCTGACGGGCTTGTCTGCTCCCGG CATCCGCTTACAGACA

AGCTGTGACCGTCTCCGGGAGCTGCATGTGTCAGAGGTTTTCACCGTCATCACCGAA ACGCGCGAGACGAAAG

GGCCTCGTGATACGCCTATTTTTATAGGTTAATGTCATGATAATAATGGTTTCTTAG ACGTCAGGTGGCACTTTTC

GGGGAAATGTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGT ATCCGCTCATGAGACAATA

ACCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTT CCGTGTCGCCCTTATTCCC

TTTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTA AAAGATGCTGAAGATCAGT

TGGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGA GTTTTCGCCCCGAAGAA

CGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGT ATTGACGCCGGGCAAGAG

CAACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTC ACAGAAAAGCATCTTACG

GATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACT GCGGCCAACTTACTTCTG

ACAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCAT GTAACTCGCCTTGATCG

TTGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCC TGTAGCAATGGCAACA

ACGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTA ATAGACTGGATGGAGGCG

GATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCT GATAAATCTGGAGCCGG

TGAGCGTGGAAGCCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCG TATCGTAGTTATCTACA

CGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTG CCTCACTGATTAAGCAT

TGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCAT TTTTAATTTAAAAGGATCTAG

GTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTC CACTGAGCGTCAGACCCC

GTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGC TTGCAAACAAAAAAACCAC

CGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGG TAACTGGCTTCAGCAGA

GCGCAGATACCAAATACTGTTCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAG AACTCTGTAGCACCGCCT

ACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCG TGTCTTACCGGGTTGGA

CTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTG CACACAGCCCAGCTTG

GAGCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCC ACGCTTCCCGAAGGGA

GAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGG AGCTTCCAGGGGGA

AACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGA TTTTTGTGATGCTCGTCA

GGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCC TTTTGCTGGCCTTTTG

CTCACATGT

1.9 NPY

Nucleotide sequence of sasgRNA for mouse NPY; sgRNA1 (SEQ ID NO: 105)

GGAGGCTGGAGCCACTGCCGC

Nucleotide sequence of sasgRNA for mouse NPY; sgRNA2 (SEQ ID NO: 106)

CTGGGGGCGGGAAGTGGCTGT

Nucleotide sequence of sasgRNA for mouse NPY; sgRNA3 (SEQ ID NO: 107)

ACTTCCCGCCCCCAGCGGCGG pAAV-CMV-sadCas9-U6gRNA(Npy-sa sgRNA1) used in in vitro qPCR experiments (SEQ ID NO: 108)

CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCGTCGGGCGACC TTTGGTCGCCCGGCC

TCAGTGAGCGAGCGAGCGCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCC TGCGGCCTCTAGACTC

GAGGCGTTGACATTGATTATTGACTAGTTATTAATAGTAATCAATTACGGGGTCATT AGTTCATAGCCCATATATG

GAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGAC CCCCGCCCATTGACGT

CAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAAT GGGTGGAGTATTTACGGT

AAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTG ACGTCAATGACGGTAAAT

GGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGT ACATCTACGTATTAGTCA

TCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAATGGGCGTGGATAGCGGT TTGACTCACGGGGATTT CCAAGTCTCCACCCCATTGACGTCAATGGGAGTTTGTTTTGGCACCAAAATCAACGGGAC TTTCCAAAATGTCGT

AACAACTCCGCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTAT ATAAGCAGAGCTCTCT

GGCTAACTACCGGTGCCACCATGGCCCCAAAGAAGAAGCGGAAGGTCGGTATCCACG GAGTCCCAGCAGCCAA

GCGGAACTACATCCTGGGCCTGGCCATCGGCATCACCAGCGTGGGCTACGGCATCAT CGACTACGAGACACGG

GACGTGATCGATGCCGGCGTGCGGCTGTTCAAAGAGGCCAACGTGGAAAACAACGAG GGCAGGCGGAGCAAG

AGAGGCGCCAGAAGGCTGAAGCGGCGGAGGCGGCATAGAATCCAGAGAGTGAAGAAG CTGCTGTTCGACTAC

AACCTGCTGACCGACCACAGCGAGCTGAGCGGCATCAACCCCTACGAGGCCAGAGTG AAGGGCCTGAGCCAG

AAGCTGAGCGAGGAAGAGTTCTCTGCCGCCCTGCTGCACCTGGCCAAGAGAAGAGGC GTGCACAACGTGAACG

AGGTGGAAGAGGACACCGGCAACGAGCTGTCCACCAAAGAGCAGATCAGCCGGAACA GCAAGGCCCTGGAAG

AGAAATACGTGGCCGAACTGCAGCTGGAACGGCTGAAGAAAGACGGCGAAGTGCGGG GCAGCATCAACAGATT

CAAGACCAGCGACTACGTGAAAGAAGCCAAACAGCTGCTGAAGGTGCAGAAGGCCTA CCACCAGCTGGACCAG

AGCTTCATCGACACCTACATCGACCTGCTGGAAACCCGGCGGACCTACTATGAGGGA CCTGGCGAGGGCAGCC

CCTTCGGCTGGAAGGACATCAAAGAATGGTACGAGATGCTGATGGGCCACTGCACCT ACTTCCCCGAGGAACT

GCGGAGCGTGAAGTACGCCTACAACGCCGACCTGTACAACGCCCTGAACGACCTGAA CAATCTCGTGATCACC

AGGGACGAGAACGAGAAGCTGGAATATTACGAGAAGTTCCAGATCATCGAGAACGTG TTCAAGCAGAAGAAGAA

GCCCACCCTGAAGCAGATCGCCAAAGAAATCCTCGTGAACGAAGAGGATATTAAGGG CTACAGAGTGACCAGCA

CCGGCAAGCCCGAGTTCACCAACCTGAAGGTGTACCACGACATCAAGGACATTACCG CCCGGAAAGAGATTATT

GAGAACGCCGAGCTGCTGGATCAGATTGCCAAGATCCTGACCATCTACCAGAGCAGC GAGGACATCCAGGAAG

AACTGACCAATCTGAACTCCGAGCTGACCCAGGAAGAGATCGAGCAGATCTCTAATC TGAAGGGCTATACCGGC

ACCCACAACCTGAGCCTGAAGGCCATCAACCTGATCCTGGACGAGCTGTGGCACACC AACGACAACCAGATCG

CTATCTTCAACCGGCTGAAGCTGGTGCCCAAGAAGGTGGACCTGTCCCAGCAGAAAG AGATCCCCACCACCCT

GGTGGACGACTTCATCCTGAGCCCCGTCGTGAAGAGAAGCTTCATCCAGAGCATCAA AGTGATCAACGCCATCA

TCAAGAAGTACGGCCTGCCCAACGACATCATTATCGAGCTGGCCCGCGAGAAGAACT CCAAGGACGCCCAGAA

AATGATCAACGAGATGCAGAAGCGGAACCGGCAGACCAACGAGCGGATCGAGGAAAT CATCCGGACCACCGGC

AAAGAGAACGCCAAGTACCTGATCGAGAAGATCAAGCTGCACGACATGCAGGAAGGC AAGTGCCTGTACAGCC

TGGAAGCCATCCCTCTGGAAGATCTGCTGAACAACCCCTTCAACTATGAGGTGGACC ACATCATCCCCAGAAGC

GTGTCCTTCGACAACAGCTTCAACAACAAGGTGCTCGTGAAGCAGGAAGAAGCCAGC AAGAAGGGCAACCGGA

CCCCATTCCAGTACCTGAGCAGCAGCGACAGCAAGATCAGCTACGAAACCTTCAAGA AGCACATCCTGAATCTG

GCCAAGGGCAAGGGCAGAATCAGCAAGACCAAGAAAGAGTATCTGCTGGAAGAACGG GACATCAACAGGTTCT

CCGTGCAGAAAGACTTCATCAACCGGAACCTGGTGGATACCAGATACGCCACCAGAG GCCTGATGAACCTGCT

GCGGAGCTACTTCAGAGTGAACAACCTGGACGTGAAAGTGAAGTCCATCAATGGCGG CTTCACCAGCTTTCTGC

GGCGGAAGTGGAAGTTTAAGAAAGAGCGGAACAAGGGGTACAAGCACCACGCCGAGG ACGCCCTGATCATTGC

CAACGCCGATTTCATCTTCAAAGAGTGGAAGAAACTGGACAAGGCCAAAAAAGTGAT GGAAAACCAGATGTTCG

AGGAAAAGCAGGCCGAGAGCATGCCCGAGATCGAAACCGAGCAGGAGTACAAAGAGA TCTTCATCACCCCCCA

CCAGATCAAGCACATTAAGGACTTCAAGGACTACAAGTACAGCCACCGGGTGGACAA GAAGCCTAATAGAGAGC

TGATTAACGACACCCTGTACTCCACCCGGAAGGACGACAAGGGCAACACCCTGATCG TGAACAATCTGAACGGC

CTGTACGACAAGGACAATGACAAGCTGAAAAAGCTGATCAACAAGAGCCCCGAAAAG CTGCTGATGTACCACCA

CGACCCCCAGACCTACCAGAAACTGAAGCTGATTATGGAACAGTACGGCGACGAGAA GAATCCCCTGTACAAGT

ACTACGAGGAAACCGGGAACTACCTGACCAAGTACTCCAAAAAGGACAACGGCCCCG TGATCAAGAAGATTAAG

TATTACGGCAACAAACTGAACGCCCATCTGGACATCACCGACGACTACCCCAACAGC AGAAACAAGGTCGTGAA

GCTGTCCCTGAAGCCCTACAGATTCGACGTGTACCTGGACAATGGCGTGTACAAGTT CGTGACCGTGAAGAATC

TGGATGTGATCAAAAAAGAAAACTACTACGAAGTGAATAGCAAGTGCTATGAGGAAG CTAAGAAGCTGAAGAAGA

TCAGCAACCAGGCCGAGTTTATCGCCTCCTTCTACAACAACGATCTGATCAAGATCA ACGGCGAGCTGTATAGA

GTGATCGGCGTGAACAACGACCTGCTGAACCGGATCGAAGTGAACATGATCGACATC ACCTACCGCGAGTACCT

GGAAAACATGAACGACAAGAGGCCCCCCAGGATCATTAAGACAATCGCCTCCAAGAC CCAGAGCATTAAGAAGT

ACAGCACAGACATTCTGGGCAACCTGTATGAAGTGAAATCTAAGAAGCACCCTCAGA TCATCAAAAAGGGCAAAA

GGCCGGCGGCCACGAAAAAGGCCGGCCAGGCAAAAAAGAAAAAGGGATCCGGACGGG CTGACGCATTGGACG

ATTTTGATCTGGATATGCTGGGAAGTGACGCCCTCGATGATTTTGACCTTGACATGC TTGGTTCGGATGCCCTTG

ATGACTTTGACCTCGACATGCTCGGCAGTGACGCCCTTGATGATTTCGACCTGGACA TGCTGATTAACTGTACAG

GCAGTGGAGAGGGCAGAGGAAGTCTGCTAACATGCGGTGACGTCGAGGAGAATCCTG GCCCAATGGCCAAGC

CTTTGTCTCAAGAAGAATCCACCCTCATTGAAAGAGCAACGGCTACAATCAACAGCA TCCCCATCTCTGAAGACT

ACAGCGTCGCCAGCGCAGCTCTCTCTAGCGACGGCCGCATCTTCACTGGTGTCAATG TATATCATTTTACTGGG

GGACCTTGTGCAGAACTCGTGGTGCTGGGCACTGCTGCTGCTGCGGCAGCTGGCAAC CTGACTTGTATCGTCG CGATCGGAAATGAGAACAGGGGCATCTTGAGCCCCTGCGGACGGTGCCGACAGGTGCTTC TCGATCTGCATCC

TGGGATCAAAGCCATAGTGAAGGACAGTGATGGACAGCCGACGGCAGTTGGGATTCG TGAATTGCTGCCCTCT

GGTTATGTGTGGGAGGGCTAAGAATTCCTAGAGCTCGCTGATCAGCCTCGACTGTGC CTTCTAGTTGCCAGCCA

TCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACT GTCCTTTCCTAATAAAAT

GAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTG GGGCAGGACAGCAAGG

GGGAGGATTGGGAAGAGAATAGCAGGCATGCTGGGGAGGTACCGAGGGCCTATTTCC CATGATTCCTTCATATT

TGCATATACGATACAAGGCTGTTAGAGAGATAATTGGAATTAATTTGACTGTAAACA CAAAGATATTAGTACAAAA

TACGTGACGTAGAAAGTAATAATTTCTTGGGTAGTTTGCAGTTTTAAAATTATGTTT TAAAATGGACTATCATATGC

TTACCGTAACTTGAAAGTATTTCGATTTCTTGGCTTTATATATCTTGTGGAAAGGAC GAAAcaccGGAGGCTGGAG

CCACTGCCGCgTTTTAGTACTCTGGAAACAGAATCTACTAAAACAAGGCAAAATGCC GTGTTTATCTCGTCAACTT

GTTGGCGAGATTTTTGCGGCCGCAGGAACCCCTAGTGATGGAGTTGGCCACTCCCTC TCTGCGCGCTCGCTCG

CTCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGGGCTTTGCCCGGGCGGCC TCAGTGAGCGAGCG

AGCGCGCAGCTGCCTGCAGGGGCGCCTGATGCGGTATTTTCTCCTTACGCATCTGTG CGGTATTTCACACCGCA

TACGTCAAAGCAACCATAGTACGCGCCCTGTAGCGGCGCATTAAGCGCGGCGGGTGT GGTGGTTACGCGCAGC

GTGACCGCTACACTTGCCAGCGCCTTAGCGCCCGCTCCTTTCGCTTTCTTCCCTTCC TTTCTCGCCACGTTCGC

CGGCTTTCCCCGTCAAGCTCTAAATCGGGGGCTCCCTTTAGGGTTCCGATTTAGTGC TTTACGGCACCTCGACC

CCAAAAAACTTGATTTGGGTGATGGTTCACGTAGTGGGCCATCGCCCTGATAGACGG TTTTTCGCCCTTTGACGT

TGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAACTGGAACAACACTCAACT CTATCTCGGGCTATTCTTT

TGATTTATAAGGGATTTTGCCGATTTCGGTCTATTGGTTAAAAAATGAGCTGATTTA ACAAAAATTTAACGCGAATT

TTAACAAAATATTAACGTTTACAATTTTATGGTGCACTCTCAGTACAATCTGCTCTG ATGCCGCATAGTTAAGCCA

GCCCCGACACCCGCCAACACCCGCTGACGCGCCCTGACGGGCTTGTCTGCTCCCGGC ATCCGCTTACAGACAA

GCTGTGACCGTCTCCGGGAGCTGCATGTGTCAGAGGTTTTCACCGTCATCACCGAAA CGCGCGAGACGAAAGG

GCCTCGTGATACGCCTATTTTTATAGGTTAATGTCATGATAATAATGGTTTCTTAGA CGTCAGGTGGCACTTTTCG

GGGAAATGTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTA TCCGCTCATGAGACAATAA

CCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTC CGTGTCGCCCTTATTCCCT

TTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAA AAGATGCTGAAGATCAGTT

GGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAG TTTTCGCCCCGAAGAAC

GTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTA TTGACGCCGGGCAAGAGC

AACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCA CAGAAAAGCATCTTACGG

ATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTG CGGCCAACTTACTTCTGA

CAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATG TAACTCGCCTTGATCGT

TGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCT GTAGCAATGGCAACAA

CGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAA TAGACTGGATGGAGGCG

GATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCT GATAAATCTGGAGCCGG

TGAGCGTGGAAGCCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCG TATCGTAGTTATCTACA

CGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTG CCTCACTGATTAAGCAT

TGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCAT TTTTAATTTAAAAGGATCTAG

GTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTC CACTGAGCGTCAGACCCC

GTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGC TTGCAAACAAAAAAACCAC

CGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGG TAACTGGCTTCAGCAGA

GCGCAGATACCAAATACTGTTCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAG AACTCTGTAGCACCGCCT

ACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCG TGTCTTACCGGGTTGGA

CTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTG CACACAGCCCAGCTTG

GAGCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCC ACGCTTCCCGAAGGGA

GAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGG AGCTTCCAGGGGGA

AACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGA TTTTTGTGATGCTCGTCA

GGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCC TTTTGCTGGCCTTTTG CTCACATGT pAAV-CMV-sadCas9-U6gRNA(Npv-sa sgRNA2) used in in vitro qPCR experiments (SEQ ID NO: 109)

CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCGTCGGGCGACC TTTGGTCGCCCGGCC

TCAGTGAGCGAGCGAGCGCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCC TGCGGCCTCTAGACTC

GAGGCGTTGACATTGATTATTGACTAGTTATTAATAGTAATCAATTACGGGGTCATT AGTTCATAGCCCATATATG GAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCC CGCCCATTGACGT

CAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAAT GGGTGGAGTATTTACGGT

AAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTG ACGTCAATGACGGTAAAT

GGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGT ACATCTACGTATTAGTCA

TCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAATGGGCGTGGATAGCGGT TTGACTCACGGGGATTT

CCAAGTCTCCACCCCATTGACGTCAATGGGAGTTTGTTTTGGCACCAAAATCAACGG GACTTTCCAAAATGTCGT

AACAACTCCGCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTAT ATAAGCAGAGCTCTCT

GGCTAACTACCGGTGCCACCATGGCCCCAAAGAAGAAGCGGAAGGTCGGTATCCACG GAGTCCCAGCAGCCAA

GCGGAACTACATCCTGGGCCTGGCCATCGGCATCACCAGCGTGGGCTACGGCATCAT CGACTACGAGACACGG

GACGTGATCGATGCCGGCGTGCGGCTGTTCAAAGAGGCCAACGTGGAAAACAACGAG GGCAGGCGGAGCAAG

AGAGGCGCCAGAAGGCTGAAGCGGCGGAGGCGGCATAGAATCCAGAGAGTGAAGAAG CTGCTGTTCGACTAC

AACCTGCTGACCGACCACAGCGAGCTGAGCGGCATCAACCCCTACGAGGCCAGAGTG AAGGGCCTGAGCCAG

AAGCTGAGCGAGGAAGAGTTCTCTGCCGCCCTGCTGCACCTGGCCAAGAGAAGAGGC GTGCACAACGTGAACG

AGGTGGAAGAGGACACCGGCAACGAGCTGTCCACCAAAGAGCAGATCAGCCGGAACA GCAAGGCCCTGGAAG

AGAAATACGTGGCCGAACTGCAGCTGGAACGGCTGAAGAAAGACGGCGAAGTGCGGG GCAGCATCAACAGATT

CAAGACCAGCGACTACGTGAAAGAAGCCAAACAGCTGCTGAAGGTGCAGAAGGCCTA CCACCAGCTGGACCAG

AGCTTCATCGACACCTACATCGACCTGCTGGAAACCCGGCGGACCTACTATGAGGGA CCTGGCGAGGGCAGCC

CCTTCGGCTGGAAGGACATCAAAGAATGGTACGAGATGCTGATGGGCCACTGCACCT ACTTCCCCGAGGAACT

GCGGAGCGTGAAGTACGCCTACAACGCCGACCTGTACAACGCCCTGAACGACCTGAA CAATCTCGTGATCACC

AGGGACGAGAACGAGAAGCTGGAATATTACGAGAAGTTCCAGATCATCGAGAACGTG TTCAAGCAGAAGAAGAA

GCCCACCCTGAAGCAGATCGCCAAAGAAATCCTCGTGAACGAAGAGGATATTAAGGG CTACAGAGTGACCAGCA

CCGGCAAGCCCGAGTTCACCAACCTGAAGGTGTACCACGACATCAAGGACATTACCG CCCGGAAAGAGATTATT

GAGAACGCCGAGCTGCTGGATCAGATTGCCAAGATCCTGACCATCTACCAGAGCAGC GAGGACATCCAGGAAG

AACTGACCAATCTGAACTCCGAGCTGACCCAGGAAGAGATCGAGCAGATCTCTAATC TGAAGGGCTATACCGGC

ACCCACAACCTGAGCCTGAAGGCCATCAACCTGATCCTGGACGAGCTGTGGCACACC AACGACAACCAGATCG

CTATCTTCAACCGGCTGAAGCTGGTGCCCAAGAAGGTGGACCTGTCCCAGCAGAAAG AGATCCCCACCACCCT

GGTGGACGACTTCATCCTGAGCCCCGTCGTGAAGAGAAGCTTCATCCAGAGCATCAA AGTGATCAACGCCATCA

TCAAGAAGTACGGCCTGCCCAACGACATCATTATCGAGCTGGCCCGCGAGAAGAACT CCAAGGACGCCCAGAA

AATGATCAACGAGATGCAGAAGCGGAACCGGCAGACCAACGAGCGGATCGAGGAAAT CATCCGGACCACCGGC

AAAGAGAACGCCAAGTACCTGATCGAGAAGATCAAGCTGCACGACATGCAGGAAGGC AAGTGCCTGTACAGCC

TGGAAGCCATCCCTCTGGAAGATCTGCTGAACAACCCCTTCAACTATGAGGTGGACC ACATCATCCCCAGAAGC

GTGTCCTTCGACAACAGCTTCAACAACAAGGTGCTCGTGAAGCAGGAAGAAGCCAGC AAGAAGGGCAACCGGA

CCCCATTCCAGTACCTGAGCAGCAGCGACAGCAAGATCAGCTACGAAACCTTCAAGA AGCACATCCTGAATCTG

GCCAAGGGCAAGGGCAGAATCAGCAAGACCAAGAAAGAGTATCTGCTGGAAGAACGG GACATCAACAGGTTCT

CCGTGCAGAAAGACTTCATCAACCGGAACCTGGTGGATACCAGATACGCCACCAGAG GCCTGATGAACCTGCT

GCGGAGCTACTTCAGAGTGAACAACCTGGACGTGAAAGTGAAGTCCATCAATGGCGG CTTCACCAGCTTTCTGC

GGCGGAAGTGGAAGTTTAAGAAAGAGCGGAACAAGGGGTACAAGCACCACGCCGAGG ACGCCCTGATCATTGC

CAACGCCGATTTCATCTTCAAAGAGTGGAAGAAACTGGACAAGGCCAAAAAAGTGAT GGAAAACCAGATGTTCG

AGGAAAAGCAGGCCGAGAGCATGCCCGAGATCGAAACCGAGCAGGAGTACAAAGAGA TCTTCATCACCCCCCA

CCAGATCAAGCACATTAAGGACTTCAAGGACTACAAGTACAGCCACCGGGTGGACAA GAAGCCTAATAGAGAGC

TGATTAACGACACCCTGTACTCCACCCGGAAGGACGACAAGGGCAACACCCTGATCG TGAACAATCTGAACGGC

CTGTACGACAAGGACAATGACAAGCTGAAAAAGCTGATCAACAAGAGCCCCGAAAAG CTGCTGATGTACCACCA

CGACCCCCAGACCTACCAGAAACTGAAGCTGATTATGGAACAGTACGGCGACGAGAA GAATCCCCTGTACAAGT

ACTACGAGGAAACCGGGAACTACCTGACCAAGTACTCCAAAAAGGACAACGGCCCCG TGATCAAGAAGATTAAG

TATTACGGCAACAAACTGAACGCCCATCTGGACATCACCGACGACTACCCCAACAGC AGAAACAAGGTCGTGAA

GCTGTCCCTGAAGCCCTACAGATTCGACGTGTACCTGGACAATGGCGTGTACAAGTT CGTGACCGTGAAGAATC

TGGATGTGATCAAAAAAGAAAACTACTACGAAGTGAATAGCAAGTGCTATGAGGAAG CTAAGAAGCTGAAGAAGA

TCAGCAACCAGGCCGAGTTTATCGCCTCCTTCTACAACAACGATCTGATCAAGATCA ACGGCGAGCTGTATAGA

GTGATCGGCGTGAACAACGACCTGCTGAACCGGATCGAAGTGAACATGATCGACATC ACCTACCGCGAGTACCT

GGAAAACATGAACGACAAGAGGCCCCCCAGGATCATTAAGACAATCGCCTCCAAGAC CCAGAGCATTAAGAAGT

ACAGCACAGACATTCTGGGCAACCTGTATGAAGTGAAATCTAAGAAGCACCCTCAGA TCATCAAAAAGGGCAAAA

GGCCGGCGGCCACGAAAAAGGCCGGCCAGGCAAAAAAGAAAAAGGGATCCGGACGGG CTGACGCATTGGACG

ATTTTGATCTGGATATGCTGGGAAGTGACGCCCTCGATGATTTTGACCTTGACATGC TTGGTTCGGATGCCCTTG ATGACTTTGACCTCGACATGCTCGGCAGTGACGCCCTTGATGATTTCGACCTGGACATGC TGATTAACTGTACAG

GCAGTGGAGAGGGCAGAGGAAGTCTGCTAACATGCGGTGACGTCGAGGAGAATCCTG GCCCAATGGCCAAGC

CTTTGTCTCAAGAAGAATCCACCCTCATTGAAAGAGCAACGGCTACAATCAACAGCA TCCCCATCTCTGAAGACT

ACAGCGTCGCCAGCGCAGCTCTCTCTAGCGACGGCCGCATCTTCACTGGTGTCAATG TATATCATTTTACTGGG

GGACCTTGTGCAGAACTCGTGGTGCTGGGCACTGCTGCTGCTGCGGCAGCTGGCAAC CTGACTTGTATCGTCG

CGATCGGAAATGAGAACAGGGGCATCTTGAGCCCCTGCGGACGGTGCCGACAGGTGC TTCTCGATCTGCATCC

TGGGATCAAAGCCATAGTGAAGGACAGTGATGGACAGCCGACGGCAGTTGGGATTCG TGAATTGCTGCCCTCT

GGTTATGTGTGGGAGGGCTAAGAATTCCTAGAGCTCGCTGATCAGCCTCGACTGTGC CTTCTAGTTGCCAGCCA

TCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACT GTCCTTTCCTAATAAAAT

GAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTG GGGCAGGACAGCAAGG

GGGAGGATTGGGAAGAGAATAGCAGGCATGCTGGGGAGGTACCGAGGGCCTATTTCC CATGATTCCTTCATATT

TGCATATACGATACAAGGCTGTTAGAGAGATAATTGGAATTAATTTGACTGTAAACA CAAAGATATTAGTACAAAA

TACGTGACGTAGAAAGTAATAATTTCTTGGGTAGTTTGCAGTTTTAAAATTATGTTT TAAAATGGACTATCATATGC

TTACCGTAACTTGAAAGTATTTCGATTTCTTGGCTTTATATATCTTGTGGAAAGGAC GAAAcaccgCTGGGGGCGG

GAAGTGGCTGTgTTTTAGTACTCTGGAAACAGAATCTACTAAAACAAGGCAAAATGC CGTGTTTATCTCGTCAACT

TGTTGGCGAGATTTTTGCGGCCGCAGGAACCCCTAGTGATGGAGTTGGCCACTCCCT CTCTGCGCGCTCGCTC

GCTCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGGGCTTTGCCCGGGCGGC CTCAGTGAGCGAGC

GAGCGCGCAGCTGCCTGCAGGGGCGCCTGATGCGGTATTTTCTCCTTACGCATCTGT GCGGTATTTCACACCG

CATACGTCAAAGCAACCATAGTACGCGCCCTGTAGCGGCGCATTAAGCGCGGCGGGT GTGGTGGTTACGCGCA

GCGTGACCGCTACACTTGCCAGCGCCTTAGCGCCCGCTCCTTTCGCTTTCTTCCCTT CCTTTCTCGCCACGTTC

GCCGGCTTTCCCCGTCAAGCTCTAAATCGGGGGCTCCCTTTAGGGTTCCGATTTAGT GCTTTACGGCACCTCGA

CCCCAAAAAACTTGATTTGGGTGATGGTTCACGTAGTGGGCCATCGCCCTGATAGAC GGTTTTTCGCCCTTTGAC

GTTGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAACTGGAACAACACTCAA CTCTATCTCGGGCTATTCT

TTTGATTTATAAGGGATTTTGCCGATTTCGGTCTATTGGTTAAAAAATGAGCTGATT TAACAAAAATTTAACGCGAA

TTTTAACAAAATATTAACGTTTACAATTTTATGGTGCACTCTCAGTACAATCTGCTC TGATGCCGCATAGTTAAGCC

AGCCCCGACACCCGCCAACACCCGCTGACGCGCCCTGACGGGCTTGTCTGCTCCCGG CATCCGCTTACAGACA

AGCTGTGACCGTCTCCGGGAGCTGCATGTGTCAGAGGTTTTCACCGTCATCACCGAA ACGCGCGAGACGAAAG

GGCCTCGTGATACGCCTATTTTTATAGGTTAATGTCATGATAATAATGGTTTCTTAG ACGTCAGGTGGCACTTTTC

GGGGAAATGTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGT ATCCGCTCATGAGACAATA

ACCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTT CCGTGTCGCCCTTATTCCC

TTTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTA AAAGATGCTGAAGATCAGT

TGGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGA GTTTTCGCCCCGAAGAA

CGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGT ATTGACGCCGGGCAAGAG

CAACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTC ACAGAAAAGCATCTTACG

GATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACT GCGGCCAACTTACTTCTG

ACAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCAT GTAACTCGCCTTGATCG

TTGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCC TGTAGCAATGGCAACA

ACGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTA ATAGACTGGATGGAGGCG

GATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCT GATAAATCTGGAGCCGG

TGAGCGTGGAAGCCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCG TATCGTAGTTATCTACA

CGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTG CCTCACTGATTAAGCAT

TGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCAT TTTTAATTTAAAAGGATCTAG

GTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTC CACTGAGCGTCAGACCCC

GTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGC TTGCAAACAAAAAAACCAC

CGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGG TAACTGGCTTCAGCAGA

GCGCAGATACCAAATACTGTTCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAG AACTCTGTAGCACCGCCT

ACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCG TGTCTTACCGGGTTGGA

CTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTG CACACAGCCCAGCTTG

GAGCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCC ACGCTTCCCGAAGGGA

GAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGG AGCTTCCAGGGGGA

AACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGA TTTTTGTGATGCTCGTCA

GGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCC TTTTGCTGGCCTTTTG

CTCACATGT pAAV-CMV-sadCas9-U6gRNA(Npy-sa sgRNA3) used in in vitro qPCR experiments (SEQ ID NO: 110)

CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCGTCGGGCGACC TTTGGTCGCCCGGCC

TCAGTGAGCGAGCGAGCGCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCC TGCGGCCTCTAGACTC

GAGGCGTTGACATTGATTATTGACTAGTTATTAATAGTAATCAATTACGGGGTCATT AGTTCATAGCCCATATATG

GAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGAC CCCCGCCCATTGACGT

CAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAAT GGGTGGAGTATTTACGGT

AAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTG ACGTCAATGACGGTAAAT

GGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGT ACATCTACGTATTAGTCA

TCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAATGGGCGTGGATAGCGGT TTGACTCACGGGGATTT

CCAAGTCTCCACCCCATTGACGTCAATGGGAGTTTGTTTTGGCACCAAAATCAACGG GACTTTCCAAAATGTCGT

AACAACTCCGCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTAT ATAAGCAGAGCTCTCT

GGCTAACTACCGGTGCCACCATGGCCCCAAAGAAGAAGCGGAAGGTCGGTATCCACG GAGTCCCAGCAGCCAA

GCGGAACTACATCCTGGGCCTGGCCATCGGCATCACCAGCGTGGGCTACGGCATCAT CGACTACGAGACACGG

GACGTGATCGATGCCGGCGTGCGGCTGTTCAAAGAGGCCAACGTGGAAAACAACGAG GGCAGGCGGAGCAAG

AGAGGCGCCAGAAGGCTGAAGCGGCGGAGGCGGCATAGAATCCAGAGAGTGAAGAAG CTGCTGTTCGACTAC

AACCTGCTGACCGACCACAGCGAGCTGAGCGGCATCAACCCCTACGAGGCCAGAGTG AAGGGCCTGAGCCAG

AAGCTGAGCGAGGAAGAGTTCTCTGCCGCCCTGCTGCACCTGGCCAAGAGAAGAGGC GTGCACAACGTGAACG

AGGTGGAAGAGGACACCGGCAACGAGCTGTCCACCAAAGAGCAGATCAGCCGGAACA GCAAGGCCCTGGAAG

AGAAATACGTGGCCGAACTGCAGCTGGAACGGCTGAAGAAAGACGGCGAAGTGCGGG GCAGCATCAACAGATT

CAAGACCAGCGACTACGTGAAAGAAGCCAAACAGCTGCTGAAGGTGCAGAAGGCCTA CCACCAGCTGGACCAG

AGCTTCATCGACACCTACATCGACCTGCTGGAAACCCGGCGGACCTACTATGAGGGA CCTGGCGAGGGCAGCC

CCTTCGGCTGGAAGGACATCAAAGAATGGTACGAGATGCTGATGGGCCACTGCACCT ACTTCCCCGAGGAACT

GCGGAGCGTGAAGTACGCCTACAACGCCGACCTGTACAACGCCCTGAACGACCTGAA CAATCTCGTGATCACC

AGGGACGAGAACGAGAAGCTGGAATATTACGAGAAGTTCCAGATCATCGAGAACGTG TTCAAGCAGAAGAAGAA

GCCCACCCTGAAGCAGATCGCCAAAGAAATCCTCGTGAACGAAGAGGATATTAAGGG CTACAGAGTGACCAGCA

CCGGCAAGCCCGAGTTCACCAACCTGAAGGTGTACCACGACATCAAGGACATTACCG CCCGGAAAGAGATTATT

GAGAACGCCGAGCTGCTGGATCAGATTGCCAAGATCCTGACCATCTACCAGAGCAGC GAGGACATCCAGGAAG

AACTGACCAATCTGAACTCCGAGCTGACCCAGGAAGAGATCGAGCAGATCTCTAATC TGAAGGGCTATACCGGC

ACCCACAACCTGAGCCTGAAGGCCATCAACCTGATCCTGGACGAGCTGTGGCACACC AACGACAACCAGATCG

CTATCTTCAACCGGCTGAAGCTGGTGCCCAAGAAGGTGGACCTGTCCCAGCAGAAAG AGATCCCCACCACCCT

GGTGGACGACTTCATCCTGAGCCCCGTCGTGAAGAGAAGCTTCATCCAGAGCATCAA AGTGATCAACGCCATCA

TCAAGAAGTACGGCCTGCCCAACGACATCATTATCGAGCTGGCCCGCGAGAAGAACT CCAAGGACGCCCAGAA

AATGATCAACGAGATGCAGAAGCGGAACCGGCAGACCAACGAGCGGATCGAGGAAAT CATCCGGACCACCGGC

AAAGAGAACGCCAAGTACCTGATCGAGAAGATCAAGCTGCACGACATGCAGGAAGGC AAGTGCCTGTACAGCC

TGGAAGCCATCCCTCTGGAAGATCTGCTGAACAACCCCTTCAACTATGAGGTGGACC ACATCATCCCCAGAAGC

GTGTCCTTCGACAACAGCTTCAACAACAAGGTGCTCGTGAAGCAGGAAGAAGCCAGC AAGAAGGGCAACCGGA

CCCCATTCCAGTACCTGAGCAGCAGCGACAGCAAGATCAGCTACGAAACCTTCAAGA AGCACATCCTGAATCTG

GCCAAGGGCAAGGGCAGAATCAGCAAGACCAAGAAAGAGTATCTGCTGGAAGAACGG GACATCAACAGGTTCT

CCGTGCAGAAAGACTTCATCAACCGGAACCTGGTGGATACCAGATACGCCACCAGAG GCCTGATGAACCTGCT

GCGGAGCTACTTCAGAGTGAACAACCTGGACGTGAAAGTGAAGTCCATCAATGGCGG CTTCACCAGCTTTCTGC

GGCGGAAGTGGAAGTTTAAGAAAGAGCGGAACAAGGGGTACAAGCACCACGCCGAGG ACGCCCTGATCATTGC

CAACGCCGATTTCATCTTCAAAGAGTGGAAGAAACTGGACAAGGCCAAAAAAGTGAT GGAAAACCAGATGTTCG

AGGAAAAGCAGGCCGAGAGCATGCCCGAGATCGAAACCGAGCAGGAGTACAAAGAGA TCTTCATCACCCCCCA

CCAGATCAAGCACATTAAGGACTTCAAGGACTACAAGTACAGCCACCGGGTGGACAA GAAGCCTAATAGAGAGC

TGATTAACGACACCCTGTACTCCACCCGGAAGGACGACAAGGGCAACACCCTGATCG TGAACAATCTGAACGGC

CTGTACGACAAGGACAATGACAAGCTGAAAAAGCTGATCAACAAGAGCCCCGAAAAG CTGCTGATGTACCACCA

CGACCCCCAGACCTACCAGAAACTGAAGCTGATTATGGAACAGTACGGCGACGAGAA GAATCCCCTGTACAAGT

ACTACGAGGAAACCGGGAACTACCTGACCAAGTACTCCAAAAAGGACAACGGCCCCG TGATCAAGAAGATTAAG

TATTACGGCAACAAACTGAACGCCCATCTGGACATCACCGACGACTACCCCAACAGC AGAAACAAGGTCGTGAA

GCTGTCCCTGAAGCCCTACAGATTCGACGTGTACCTGGACAATGGCGTGTACAAGTT CGTGACCGTGAAGAATC

TGGATGTGATCAAAAAAGAAAACTACTACGAAGTGAATAGCAAGTGCTATGAGGAAG CTAAGAAGCTGAAGAAGA

TCAGCAACCAGGCCGAGTTTATCGCCTCCTTCTACAACAACGATCTGATCAAGATCA ACGGCGAGCTGTATAGA

GTGATCGGCGTGAACAACGACCTGCTGAACCGGATCGAAGTGAACATGATCGACATC ACCTACCGCGAGTACCT GGAAAACATGAACGACAAGAGGCCCCCCAGGATCATTAAGACAATCGCCTCCAAGACCCA GAGCATTAAGAAGT

ACAGCACAGACATTCTGGGCAACCTGTATGAAGTGAAATCTAAGAAGCACCCTCAGA TCATCAAAAAGGGCAAAA

GGCCGGCGGCCACGAAAAAGGCCGGCCAGGCAAAAAAGAAAAAGGGATCCGGACGGG CTGACGCATTGGACG

ATTTTGATCTGGATATGCTGGGAAGTGACGCCCTCGATGATTTTGACCTTGACATGC TTGGTTCGGATGCCCTTG

ATGACTTTGACCTCGACATGCTCGGCAGTGACGCCCTTGATGATTTCGACCTGGACA TGCTGATTAACTGTACAG

GCAGTGGAGAGGGCAGAGGAAGTCTGCTAACATGCGGTGACGTCGAGGAGAATCCTG GCCCAATGGCCAAGC

CTTTGTCTCAAGAAGAATCCACCCTCATTGAAAGAGCAACGGCTACAATCAACAGCA TCCCCATCTCTGAAGACT

ACAGCGTCGCCAGCGCAGCTCTCTCTAGCGACGGCCGCATCTTCACTGGTGTCAATG TATATCATTTTACTGGG

GGACCTTGTGCAGAACTCGTGGTGCTGGGCACTGCTGCTGCTGCGGCAGCTGGCAAC CTGACTTGTATCGTCG

CGATCGGAAATGAGAACAGGGGCATCTTGAGCCCCTGCGGACGGTGCCGACAGGTGC TTCTCGATCTGCATCC

TGGGATCAAAGCCATAGTGAAGGACAGTGATGGACAGCCGACGGCAGTTGGGATTCG TGAATTGCTGCCCTCT

GGTTATGTGTGGGAGGGCTAAGAATTCCTAGAGCTCGCTGATCAGCCTCGACTGTGC CTTCTAGTTGCCAGCCA

TCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACT GTCCTTTCCTAATAAAAT

GAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTG GGGCAGGACAGCAAGG

GGGAGGATTGGGAAGAGAATAGCAGGCATGCTGGGGAGGTACCGAGGGCCTATTTCC CATGATTCCTTCATATT

TGCATATACGATACAAGGCTGTTAGAGAGATAATTGGAATTAATTTGACTGTAAACA CAAAGATATTAGTACAAAA

TACGTGACGTAGAAAGTAATAATTTCTTGGGTAGTTTGCAGTTTTAAAATTATGTTT TAAAATGGACTATCATATGC

TTACCGTAACTTGAAAGTATTTCGATTTCTTGGCTTTATATATCTTGTGGAAAGGAC GAAAcaccgACTTCCCGCCC

CCAGCGGCGGgTTTTAGTACTCTGGAAACAGAATCTACTAAAACAAGGCAAAATGCC GTGTTTATCTCGTCAACT

TGTTGGCGAGATTTTTGCGGCCGCAGGAACCCCTAGTGATGGAGTTGGCCACTCCCT CTCTGCGCGCTCGCTC

GCTCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGGGCTTTGCCCGGGCGGC CTCAGTGAGCGAGC

GAGCGCGCAGCTGCCTGCAGGGGCGCCTGATGCGGTATTTTCTCCTTACGCATCTGT GCGGTATTTCACACCG

CATACGTCAAAGCAACCATAGTACGCGCCCTGTAGCGGCGCATTAAGCGCGGCGGGT GTGGTGGTTACGCGCA

GCGTGACCGCTACACTTGCCAGCGCCTTAGCGCCCGCTCCTTTCGCTTTCTTCCCTT CCTTTCTCGCCACGTTC

GCCGGCTTTCCCCGTCAAGCTCTAAATCGGGGGCTCCCTTTAGGGTTCCGATTTAGT GCTTTACGGCACCTCGA

CCCCAAAAAACTTGATTTGGGTGATGGTTCACGTAGTGGGCCATCGCCCTGATAGAC GGTTTTTCGCCCTTTGAC

GTTGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAACTGGAACAACACTCAA CTCTATCTCGGGCTATTCT

TTTGATTTATAAGGGATTTTGCCGATTTCGGTCTATTGGTTAAAAAATGAGCTGATT TAACAAAAATTTAACGCGAA

TTTTAACAAAATATTAACGTTTACAATTTTATGGTGCACTCTCAGTACAATCTGCTC TGATGCCGCATAGTTAAGCC

AGCCCCGACACCCGCCAACACCCGCTGACGCGCCCTGACGGGCTTGTCTGCTCCCGG CATCCGCTTACAGACA

AGCTGTGACCGTCTCCGGGAGCTGCATGTGTCAGAGGTTTTCACCGTCATCACCGAA ACGCGCGAGACGAAAG

GGCCTCGTGATACGCCTATTTTTATAGGTTAATGTCATGATAATAATGGTTTCTTAG ACGTCAGGTGGCACTTTTC

GGGGAAATGTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGT ATCCGCTCATGAGACAATA

ACCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTT CCGTGTCGCCCTTATTCCC

TTTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTA AAAGATGCTGAAGATCAGT

TGGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGA GTTTTCGCCCCGAAGAA

CGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGT ATTGACGCCGGGCAAGAG

CAACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTC ACAGAAAAGCATCTTACG

GATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACT GCGGCCAACTTACTTCTG

ACAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCAT GTAACTCGCCTTGATCG

TTGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCC TGTAGCAATGGCAACA

ACGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTA ATAGACTGGATGGAGGCG

GATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCT GATAAATCTGGAGCCGG

TGAGCGTGGAAGCCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCG TATCGTAGTTATCTACA

CGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTG CCTCACTGATTAAGCAT

TGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCAT TTTTAATTTAAAAGGATCTAG

GTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTC CACTGAGCGTCAGACCCC

GTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGC TTGCAAACAAAAAAACCAC

CGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGG TAACTGGCTTCAGCAGA

GCGCAGATACCAAATACTGTTCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAG AACTCTGTAGCACCGCCT

ACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCG TGTCTTACCGGGTTGGA

CTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTG CACACAGCCCAGCTTG

GAGCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCC ACGCTTCCCGAAGGGA GAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGGAGC TTCCAGGGGGA

AACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGA TTTTTGTGATGCTCGTCA

GGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCC TTTTGCTGGCCTTTTG

CTCACATGT

1.10 NPYR2

Nucleotide sequence of sasgRNA for mouse NPYR2; sgRNA1 (SEQ ID NO: 111)

GGTAGGGGAACTGCGGAGCGA

Nucleotide sequence of sasgRNA for mouse NPYR2; sgRNA2 (SEQ ID NO: 112)

AAGGACACAGGTAGGGGAACT

Nucleotide sequence of sasgRNA for mouse NPYR2; sgRNA3 (SEQ ID NO: 113)

GGAGGAGGATCGGAGATAGAA pAAV-CMV-sadCas9-U6gRNA(Npyr2-sa sgRNA1) used in in vitro qPCR experiments (SEQ ID NO: 114)

CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCGTCGGGCGACC TTTGGTCGCCCGGCC

TCAGTGAGCGAGCGAGCGCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCC TGCGGCCTCTAGACTC

GAGGCGTTGACATTGATTATTGACTAGTTATTAATAGTAATCAATTACGGGGTCATT AGTTCATAGCCCATATATG

GAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGAC CCCCGCCCATTGACGT

CAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAAT GGGTGGAGTATTTACGGT

AAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTG ACGTCAATGACGGTAAAT

GGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGT ACATCTACGTATTAGTCA

TCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAATGGGCGTGGATAGCGGT TTGACTCACGGGGATTT

CCAAGTCTCCACCCCATTGACGTCAATGGGAGTTTGTTTTGGCACCAAAATCAACGG GACTTTCCAAAATGTCGT

AACAACTCCGCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTAT ATAAGCAGAGCTCTCT

GGCTAACTACCGGTGCCACCATGGCCCCAAAGAAGAAGCGGAAGGTCGGTATCCACG GAGTCCCAGCAGCCAA

GCGGAACTACATCCTGGGCCTGGCCATCGGCATCACCAGCGTGGGCTACGGCATCAT CGACTACGAGACACGG

GACGTGATCGATGCCGGCGTGCGGCTGTTCAAAGAGGCCAACGTGGAAAACAACGAG GGCAGGCGGAGCAAG

AGAGGCGCCAGAAGGCTGAAGCGGCGGAGGCGGCATAGAATCCAGAGAGTGAAGAAG CTGCTGTTCGACTAC

AACCTGCTGACCGACCACAGCGAGCTGAGCGGCATCAACCCCTACGAGGCCAGAGTG AAGGGCCTGAGCCAG

AAGCTGAGCGAGGAAGAGTTCTCTGCCGCCCTGCTGCACCTGGCCAAGAGAAGAGGC GTGCACAACGTGAACG

AGGTGGAAGAGGACACCGGCAACGAGCTGTCCACCAAAGAGCAGATCAGCCGGAACA GCAAGGCCCTGGAAG

AGAAATACGTGGCCGAACTGCAGCTGGAACGGCTGAAGAAAGACGGCGAAGTGCGGG GCAGCATCAACAGATT

CAAGACCAGCGACTACGTGAAAGAAGCCAAACAGCTGCTGAAGGTGCAGAAGGCCTA CCACCAGCTGGACCAG

AGCTTCATCGACACCTACATCGACCTGCTGGAAACCCGGCGGACCTACTATGAGGGA CCTGGCGAGGGCAGCC

CCTTCGGCTGGAAGGACATCAAAGAATGGTACGAGATGCTGATGGGCCACTGCACCT ACTTCCCCGAGGAACT

GCGGAGCGTGAAGTACGCCTACAACGCCGACCTGTACAACGCCCTGAACGACCTGAA CAATCTCGTGATCACC

AGGGACGAGAACGAGAAGCTGGAATATTACGAGAAGTTCCAGATCATCGAGAACGTG TTCAAGCAGAAGAAGAA

GCCCACCCTGAAGCAGATCGCCAAAGAAATCCTCGTGAACGAAGAGGATATTAAGGG CTACAGAGTGACCAGCA

CCGGCAAGCCCGAGTTCACCAACCTGAAGGTGTACCACGACATCAAGGACATTACCG CCCGGAAAGAGATTATT

GAGAACGCCGAGCTGCTGGATCAGATTGCCAAGATCCTGACCATCTACCAGAGCAGC GAGGACATCCAGGAAG

AACTGACCAATCTGAACTCCGAGCTGACCCAGGAAGAGATCGAGCAGATCTCTAATC TGAAGGGCTATACCGGC

ACCCACAACCTGAGCCTGAAGGCCATCAACCTGATCCTGGACGAGCTGTGGCACACC AACGACAACCAGATCG

CTATCTTCAACCGGCTGAAGCTGGTGCCCAAGAAGGTGGACCTGTCCCAGCAGAAAG AGATCCCCACCACCCT

GGTGGACGACTTCATCCTGAGCCCCGTCGTGAAGAGAAGCTTCATCCAGAGCATCAA AGTGATCAACGCCATCA

TCAAGAAGTACGGCCTGCCCAACGACATCATTATCGAGCTGGCCCGCGAGAAGAACT CCAAGGACGCCCAGAA

AATGATCAACGAGATGCAGAAGCGGAACCGGCAGACCAACGAGCGGATCGAGGAAAT CATCCGGACCACCGGC

AAAGAGAACGCCAAGTACCTGATCGAGAAGATCAAGCTGCACGACATGCAGGAAGGC AAGTGCCTGTACAGCC

TGGAAGCCATCCCTCTGGAAGATCTGCTGAACAACCCCTTCAACTATGAGGTGGACC ACATCATCCCCAGAAGC

GTGTCCTTCGACAACAGCTTCAACAACAAGGTGCTCGTGAAGCAGGAAGAAGCCAGC AAGAAGGGCAACCGGA CCCCATTCCAGTACCTGAGCAGCAGCGACAGCAAGATCAGCTACGAAACCTTCAAGAAGC ACATCCTGAATCTG

GCCAAGGGCAAGGGCAGAATCAGCAAGACCAAGAAAGAGTATCTGCTGGAAGAACGG GACATCAACAGGTTCT

CCGTGCAGAAAGACTTCATCAACCGGAACCTGGTGGATACCAGATACGCCACCAGAG GCCTGATGAACCTGCT

GCGGAGCTACTTCAGAGTGAACAACCTGGACGTGAAAGTGAAGTCCATCAATGGCGG CTTCACCAGCTTTCTGC

GGCGGAAGTGGAAGTTTAAGAAAGAGCGGAACAAGGGGTACAAGCACCACGCCGAGG ACGCCCTGATCATTGC

CAACGCCGATTTCATCTTCAAAGAGTGGAAGAAACTGGACAAGGCCAAAAAAGTGAT GGAAAACCAGATGTTCG

AGGAAAAGCAGGCCGAGAGCATGCCCGAGATCGAAACCGAGCAGGAGTACAAAGAGA TCTTCATCACCCCCCA

CCAGATCAAGCACATTAAGGACTTCAAGGACTACAAGTACAGCCACCGGGTGGACAA GAAGCCTAATAGAGAGC

TGATTAACGACACCCTGTACTCCACCCGGAAGGACGACAAGGGCAACACCCTGATCG TGAACAATCTGAACGGC

CTGTACGACAAGGACAATGACAAGCTGAAAAAGCTGATCAACAAGAGCCCCGAAAAG CTGCTGATGTACCACCA

CGACCCCCAGACCTACCAGAAACTGAAGCTGATTATGGAACAGTACGGCGACGAGAA GAATCCCCTGTACAAGT

ACTACGAGGAAACCGGGAACTACCTGACCAAGTACTCCAAAAAGGACAACGGCCCCG TGATCAAGAAGATTAAG

TATTACGGCAACAAACTGAACGCCCATCTGGACATCACCGACGACTACCCCAACAGC AGAAACAAGGTCGTGAA

GCTGTCCCTGAAGCCCTACAGATTCGACGTGTACCTGGACAATGGCGTGTACAAGTT CGTGACCGTGAAGAATC

TGGATGTGATCAAAAAAGAAAACTACTACGAAGTGAATAGCAAGTGCTATGAGGAAG CTAAGAAGCTGAAGAAGA

TCAGCAACCAGGCCGAGTTTATCGCCTCCTTCTACAACAACGATCTGATCAAGATCA ACGGCGAGCTGTATAGA

GTGATCGGCGTGAACAACGACCTGCTGAACCGGATCGAAGTGAACATGATCGACATC ACCTACCGCGAGTACCT

GGAAAACATGAACGACAAGAGGCCCCCCAGGATCATTAAGACAATCGCCTCCAAGAC CCAGAGCATTAAGAAGT

ACAGCACAGACATTCTGGGCAACCTGTATGAAGTGAAATCTAAGAAGCACCCTCAGA TCATCAAAAAGGGCAAAA

GGCCGGCGGCCACGAAAAAGGCCGGCCAGGCAAAAAAGAAAAAGGGATCCGGACGGG CTGACGCATTGGACG

ATTTTGATCTGGATATGCTGGGAAGTGACGCCCTCGATGATTTTGACCTTGACATGC TTGGTTCGGATGCCCTTG

ATGACTTTGACCTCGACATGCTCGGCAGTGACGCCCTTGATGATTTCGACCTGGACA TGCTGATTAACTGTACAG

GCAGTGGAGAGGGCAGAGGAAGTCTGCTAACATGCGGTGACGTCGAGGAGAATCCTG GCCCAATGGCCAAGC

CTTTGTCTCAAGAAGAATCCACCCTCATTGAAAGAGCAACGGCTACAATCAACAGCA TCCCCATCTCTGAAGACT

ACAGCGTCGCCAGCGCAGCTCTCTCTAGCGACGGCCGCATCTTCACTGGTGTCAATG TATATCATTTTACTGGG

GGACCTTGTGCAGAACTCGTGGTGCTGGGCACTGCTGCTGCTGCGGCAGCTGGCAAC CTGACTTGTATCGTCG

CGATCGGAAATGAGAACAGGGGCATCTTGAGCCCCTGCGGACGGTGCCGACAGGTGC TTCTCGATCTGCATCC

TGGGATCAAAGCCATAGTGAAGGACAGTGATGGACAGCCGACGGCAGTTGGGATTCG TGAATTGCTGCCCTCT

GGTTATGTGTGGGAGGGCTAAGAATTCCTAGAGCTCGCTGATCAGCCTCGACTGTGC CTTCTAGTTGCCAGCCA

TCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACT GTCCTTTCCTAATAAAAT

GAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTG GGGCAGGACAGCAAGG

GGGAGGATTGGGAAGAGAATAGCAGGCATGCTGGGGAGGTACCGAGGGCCTATTTCC CATGATTCCTTCATATT

TGCATATACGATACAAGGCTGTTAGAGAGATAATTGGAATTAATTTGACTGTAAACA CAAAGATATTAGTACAAAA

TACGTGACGTAGAAAGTAATAATTTCTTGGGTAGTTTGCAGTTTTAAAATTATGTTT TAAAATGGACTATCATATGC

TTACCGTAACTTGAAAGTATTTCGATTTCTTGGCTTTATATATCTTGTGGAAAGGAC GAAAcaccGGTAGGGGAACT

GCGGAGCGAgTTTTAGTACTCTGGAAACAGAATCTACTAAAACAAGGCAAAATGCCG TGTTTATCTCGTCAACTT

GTTGGCGAGATTTTTGCGGCCGCAGGAACCCCTAGTGATGGAGTTGGCCACTCCCTC TCTGCGCGCTCGCTCG

CTCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGGGCTTTGCCCGGGCGGCC TCAGTGAGCGAGCG

AGCGCGCAGCTGCCTGCAGGGGCGCCTGATGCGGTATTTTCTCCTTACGCATCTGTG CGGTATTTCACACCGCA

TACGTCAAAGCAACCATAGTACGCGCCCTGTAGCGGCGCATTAAGCGCGGCGGGTGT GGTGGTTACGCGCAGC

GTGACCGCTACACTTGCCAGCGCCTTAGCGCCCGCTCCTTTCGCTTTCTTCCCTTCC TTTCTCGCCACGTTCGC

CGGCTTTCCCCGTCAAGCTCTAAATCGGGGGCTCCCTTTAGGGTTCCGATTTAGTGC TTTACGGCACCTCGACC

CCAAAAAACTTGATTTGGGTGATGGTTCACGTAGTGGGCCATCGCCCTGATAGACGG TTTTTCGCCCTTTGACGT

TGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAACTGGAACAACACTCAACT CTATCTCGGGCTATTCTTT

TGATTTATAAGGGATTTTGCCGATTTCGGTCTATTGGTTAAAAAATGAGCTGATTTA ACAAAAATTTAACGCGAATT

TTAACAAAATATTAACGTTTACAATTTTATGGTGCACTCTCAGTACAATCTGCTCTG ATGCCGCATAGTTAAGCCA

GCCCCGACACCCGCCAACACCCGCTGACGCGCCCTGACGGGCTTGTCTGCTCCCGGC ATCCGCTTACAGACAA

GCTGTGACCGTCTCCGGGAGCTGCATGTGTCAGAGGTTTTCACCGTCATCACCGAAA CGCGCGAGACGAAAGG

GCCTCGTGATACGCCTATTTTTATAGGTTAATGTCATGATAATAATGGTTTCTTAGA CGTCAGGTGGCACTTTTCG

GGGAAATGTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTA TCCGCTCATGAGACAATAA

CCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTC CGTGTCGCCCTTATTCCCT

TTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAA AAGATGCTGAAGATCAGTT

GGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAG TTTTCGCCCCGAAGAAC GTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTATTG ACGCCGGGCAAGAGC

AACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCA CAGAAAAGCATCTTACGG

ATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTG CGGCCAACTTACTTCTGA

CAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATG TAACTCGCCTTGATCGT

TGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCT GTAGCAATGGCAACAA

CGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAA TAGACTGGATGGAGGCG

GATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCT GATAAATCTGGAGCCGG

TGAGCGTGGAAGCCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCG TATCGTAGTTATCTACA

CGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTG CCTCACTGATTAAGCAT

TGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCAT TTTTAATTTAAAAGGATCTAG

GTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTC CACTGAGCGTCAGACCCC

GTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGC TTGCAAACAAAAAAACCAC

CGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGG TAACTGGCTTCAGCAGA

GCGCAGATACCAAATACTGTTCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAG AACTCTGTAGCACCGCCT

ACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCG TGTCTTACCGGGTTGGA

CTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTG CACACAGCCCAGCTTG

GAGCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCC ACGCTTCCCGAAGGGA

GAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGG AGCTTCCAGGGGGA

AACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGA TTTTTGTGATGCTCGTCA

GGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCC TTTTGCTGGCCTTTTG

CTCACATGT pAAV-CMV-sadCas9-U6gRNA(Npyr2-sa sgRNA2) used in in vitro qPCR experiments (SEQ ID NO: 115)

CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCGTCGGGCGACC TTTGGTCGCCCGGCC

TCAGTGAGCGAGCGAGCGCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCC TGCGGCCTCTAGACTC

GAGGCGTTGACATTGATTATTGACTAGTTATTAATAGTAATCAATTACGGGGTCATT AGTTCATAGCCCATATATG

GAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGAC CCCCGCCCATTGACGT

CAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAAT GGGTGGAGTATTTACGGT

AAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTG ACGTCAATGACGGTAAAT

GGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGT ACATCTACGTATTAGTCA

TCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAATGGGCGTGGATAGCGGT TTGACTCACGGGGATTT

CCAAGTCTCCACCCCATTGACGTCAATGGGAGTTTGTTTTGGCACCAAAATCAACGG GACTTTCCAAAATGTCGT

AACAACTCCGCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTAT ATAAGCAGAGCTCTCT

GGCTAACTACCGGTGCCACCATGGCCCCAAAGAAGAAGCGGAAGGTCGGTATCCACG GAGTCCCAGCAGCCAA

GCGGAACTACATCCTGGGCCTGGCCATCGGCATCACCAGCGTGGGCTACGGCATCAT CGACTACGAGACACGG

GACGTGATCGATGCCGGCGTGCGGCTGTTCAAAGAGGCCAACGTGGAAAACAACGAG GGCAGGCGGAGCAAG

AGAGGCGCCAGAAGGCTGAAGCGGCGGAGGCGGCATAGAATCCAGAGAGTGAAGAAG CTGCTGTTCGACTAC

AACCTGCTGACCGACCACAGCGAGCTGAGCGGCATCAACCCCTACGAGGCCAGAGTG AAGGGCCTGAGCCAG

AAGCTGAGCGAGGAAGAGTTCTCTGCCGCCCTGCTGCACCTGGCCAAGAGAAGAGGC GTGCACAACGTGAACG

AGGTGGAAGAGGACACCGGCAACGAGCTGTCCACCAAAGAGCAGATCAGCCGGAACA GCAAGGCCCTGGAAG

AGAAATACGTGGCCGAACTGCAGCTGGAACGGCTGAAGAAAGACGGCGAAGTGCGGG GCAGCATCAACAGATT

CAAGACCAGCGACTACGTGAAAGAAGCCAAACAGCTGCTGAAGGTGCAGAAGGCCTA CCACCAGCTGGACCAG

AGCTTCATCGACACCTACATCGACCTGCTGGAAACCCGGCGGACCTACTATGAGGGA CCTGGCGAGGGCAGCC

CCTTCGGCTGGAAGGACATCAAAGAATGGTACGAGATGCTGATGGGCCACTGCACCT ACTTCCCCGAGGAACT

GCGGAGCGTGAAGTACGCCTACAACGCCGACCTGTACAACGCCCTGAACGACCTGAA CAATCTCGTGATCACC

AGGGACGAGAACGAGAAGCTGGAATATTACGAGAAGTTCCAGATCATCGAGAACGTG TTCAAGCAGAAGAAGAA

GCCCACCCTGAAGCAGATCGCCAAAGAAATCCTCGTGAACGAAGAGGATATTAAGGG CTACAGAGTGACCAGCA

CCGGCAAGCCCGAGTTCACCAACCTGAAGGTGTACCACGACATCAAGGACATTACCG CCCGGAAAGAGATTATT

GAGAACGCCGAGCTGCTGGATCAGATTGCCAAGATCCTGACCATCTACCAGAGCAGC GAGGACATCCAGGAAG

AACTGACCAATCTGAACTCCGAGCTGACCCAGGAAGAGATCGAGCAGATCTCTAATC TGAAGGGCTATACCGGC

ACCCACAACCTGAGCCTGAAGGCCATCAACCTGATCCTGGACGAGCTGTGGCACACC AACGACAACCAGATCG

CTATCTTCAACCGGCTGAAGCTGGTGCCCAAGAAGGTGGACCTGTCCCAGCAGAAAG AGATCCCCACCACCCT

GGTGGACGACTTCATCCTGAGCCCCGTCGTGAAGAGAAGCTTCATCCAGAGCATCAA AGTGATCAACGCCATCA TCAAGAAGTACGGCCTGCCCAACGACATCATTATCGAGCTGGCCCGCGAGAAGAACTCCA AGGACGCCCAGAA

AATGATCAACGAGATGCAGAAGCGGAACCGGCAGACCAACGAGCGGATCGAGGAAAT CATCCGGACCACCGGC

AAAGAGAACGCCAAGTACCTGATCGAGAAGATCAAGCTGCACGACATGCAGGAAGGC AAGTGCCTGTACAGCC

TGGAAGCCATCCCTCTGGAAGATCTGCTGAACAACCCCTTCAACTATGAGGTGGACC ACATCATCCCCAGAAGC

GTGTCCTTCGACAACAGCTTCAACAACAAGGTGCTCGTGAAGCAGGAAGAAGCCAGC AAGAAGGGCAACCGGA

CCCCATTCCAGTACCTGAGCAGCAGCGACAGCAAGATCAGCTACGAAACCTTCAAGA AGCACATCCTGAATCTG

GCCAAGGGCAAGGGCAGAATCAGCAAGACCAAGAAAGAGTATCTGCTGGAAGAACGG GACATCAACAGGTTCT

CCGTGCAGAAAGACTTCATCAACCGGAACCTGGTGGATACCAGATACGCCACCAGAG GCCTGATGAACCTGCT

GCGGAGCTACTTCAGAGTGAACAACCTGGACGTGAAAGTGAAGTCCATCAATGGCGG CTTCACCAGCTTTCTGC

GGCGGAAGTGGAAGTTTAAGAAAGAGCGGAACAAGGGGTACAAGCACCACGCCGAGG ACGCCCTGATCATTGC

CAACGCCGATTTCATCTTCAAAGAGTGGAAGAAACTGGACAAGGCCAAAAAAGTGAT GGAAAACCAGATGTTCG

AGGAAAAGCAGGCCGAGAGCATGCCCGAGATCGAAACCGAGCAGGAGTACAAAGAGA TCTTCATCACCCCCCA

CCAGATCAAGCACATTAAGGACTTCAAGGACTACAAGTACAGCCACCGGGTGGACAA GAAGCCTAATAGAGAGC

TGATTAACGACACCCTGTACTCCACCCGGAAGGACGACAAGGGCAACACCCTGATCG TGAACAATCTGAACGGC

CTGTACGACAAGGACAATGACAAGCTGAAAAAGCTGATCAACAAGAGCCCCGAAAAG CTGCTGATGTACCACCA

CGACCCCCAGACCTACCAGAAACTGAAGCTGATTATGGAACAGTACGGCGACGAGAA GAATCCCCTGTACAAGT

ACTACGAGGAAACCGGGAACTACCTGACCAAGTACTCCAAAAAGGACAACGGCCCCG TGATCAAGAAGATTAAG

TATTACGGCAACAAACTGAACGCCCATCTGGACATCACCGACGACTACCCCAACAGC AGAAACAAGGTCGTGAA

GCTGTCCCTGAAGCCCTACAGATTCGACGTGTACCTGGACAATGGCGTGTACAAGTT CGTGACCGTGAAGAATC

TGGATGTGATCAAAAAAGAAAACTACTACGAAGTGAATAGCAAGTGCTATGAGGAAG CTAAGAAGCTGAAGAAGA

TCAGCAACCAGGCCGAGTTTATCGCCTCCTTCTACAACAACGATCTGATCAAGATCA ACGGCGAGCTGTATAGA

GTGATCGGCGTGAACAACGACCTGCTGAACCGGATCGAAGTGAACATGATCGACATC ACCTACCGCGAGTACCT

GGAAAACATGAACGACAAGAGGCCCCCCAGGATCATTAAGACAATCGCCTCCAAGAC CCAGAGCATTAAGAAGT

ACAGCACAGACATTCTGGGCAACCTGTATGAAGTGAAATCTAAGAAGCACCCTCAGA TCATCAAAAAGGGCAAAA

GGCCGGCGGCCACGAAAAAGGCCGGCCAGGCAAAAAAGAAAAAGGGATCCGGACGGG CTGACGCATTGGACG

ATTTTGATCTGGATATGCTGGGAAGTGACGCCCTCGATGATTTTGACCTTGACATGC TTGGTTCGGATGCCCTTG

ATGACTTTGACCTCGACATGCTCGGCAGTGACGCCCTTGATGATTTCGACCTGGACA TGCTGATTAACTGTACAG

GCAGTGGAGAGGGCAGAGGAAGTCTGCTAACATGCGGTGACGTCGAGGAGAATCCTG GCCCAATGGCCAAGC

CTTTGTCTCAAGAAGAATCCACCCTCATTGAAAGAGCAACGGCTACAATCAACAGCA TCCCCATCTCTGAAGACT

ACAGCGTCGCCAGCGCAGCTCTCTCTAGCGACGGCCGCATCTTCACTGGTGTCAATG TATATCATTTTACTGGG

GGACCTTGTGCAGAACTCGTGGTGCTGGGCACTGCTGCTGCTGCGGCAGCTGGCAAC CTGACTTGTATCGTCG

CGATCGGAAATGAGAACAGGGGCATCTTGAGCCCCTGCGGACGGTGCCGACAGGTGC TTCTCGATCTGCATCC

TGGGATCAAAGCCATAGTGAAGGACAGTGATGGACAGCCGACGGCAGTTGGGATTCG TGAATTGCTGCCCTCT

GGTTATGTGTGGGAGGGCTAAGAATTCCTAGAGCTCGCTGATCAGCCTCGACTGTGC CTTCTAGTTGCCAGCCA

TCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACT GTCCTTTCCTAATAAAAT

GAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTG GGGCAGGACAGCAAGG

GGGAGGATTGGGAAGAGAATAGCAGGCATGCTGGGGAGGTACCGAGGGCCTATTTCC CATGATTCCTTCATATT

TGCATATACGATACAAGGCTGTTAGAGAGATAATTGGAATTAATTTGACTGTAAACA CAAAGATATTAGTACAAAA

TACGTGACGTAGAAAGTAATAATTTCTTGGGTAGTTTGCAGTTTTAAAATTATGTTT TAAAATGGACTATCATATGC

TTACCGTAACTTGAAAGTATTTCGATTTCTTGGCTTTATATATCTTGTGGAAAGGAC GAAAcaccgAAGGACACAGG

TAGGGGAACTgTTTTAGTACTCTGGAAACAGAATCTACTAAAACAAGGCAAAATGCC GTGTTTATCTCGTCAACTT

GTTGGCGAGATTTTTGCGGCCGCAGGAACCCCTAGTGATGGAGTTGGCCACTCCCTC TCTGCGCGCTCGCTCG

CTCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGGGCTTTGCCCGGGCGGCC TCAGTGAGCGAGCG

AGCGCGCAGCTGCCTGCAGGGGCGCCTGATGCGGTATTTTCTCCTTACGCATCTGTG CGGTATTTCACACCGCA

TACGTCAAAGCAACCATAGTACGCGCCCTGTAGCGGCGCATTAAGCGCGGCGGGTGT GGTGGTTACGCGCAGC

GTGACCGCTACACTTGCCAGCGCCTTAGCGCCCGCTCCTTTCGCTTTCTTCCCTTCC TTTCTCGCCACGTTCGC

CGGCTTTCCCCGTCAAGCTCTAAATCGGGGGCTCCCTTTAGGGTTCCGATTTAGTGC TTTACGGCACCTCGACC

CCAAAAAACTTGATTTGGGTGATGGTTCACGTAGTGGGCCATCGCCCTGATAGACGG TTTTTCGCCCTTTGACGT

TGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAACTGGAACAACACTCAACT CTATCTCGGGCTATTCTTT

TGATTTATAAGGGATTTTGCCGATTTCGGTCTATTGGTTAAAAAATGAGCTGATTTA ACAAAAATTTAACGCGAATT

TTAACAAAATATTAACGTTTACAATTTTATGGTGCACTCTCAGTACAATCTGCTCTG ATGCCGCATAGTTAAGCCA

GCCCCGACACCCGCCAACACCCGCTGACGCGCCCTGACGGGCTTGTCTGCTCCCGGC ATCCGCTTACAGACAA

GCTGTGACCGTCTCCGGGAGCTGCATGTGTCAGAGGTTTTCACCGTCATCACCGAAA CGCGCGAGACGAAAGG GCCTCGTGATACGCCTATTTTTATAGGTTAATGTCATGATAATAATGGTTTCTTAGACGT CAGGTGGCACTTTTCG

GGGAAATGTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTA TCCGCTCATGAGACAATAA

CCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTC CGTGTCGCCCTTATTCCCT

TTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAA AAGATGCTGAAGATCAGTT

GGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAG TTTTCGCCCCGAAGAAC

GTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTA TTGACGCCGGGCAAGAGC

AACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCA CAGAAAAGCATCTTACGG

ATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTG CGGCCAACTTACTTCTGA

CAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATG TAACTCGCCTTGATCGT

TGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCT GTAGCAATGGCAACAA

CGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAA TAGACTGGATGGAGGCG

GATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCT GATAAATCTGGAGCCGG

TGAGCGTGGAAGCCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCG TATCGTAGTTATCTACA

CGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTG CCTCACTGATTAAGCAT

TGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCAT TTTTAATTTAAAAGGATCTAG

GTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTC CACTGAGCGTCAGACCCC

GTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGC TTGCAAACAAAAAAACCAC

CGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGG TAACTGGCTTCAGCAGA

GCGCAGATACCAAATACTGTTCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAG AACTCTGTAGCACCGCCT

ACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCG TGTCTTACCGGGTTGGA

CTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTG CACACAGCCCAGCTTG

GAGCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCC ACGCTTCCCGAAGGGA

GAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGG AGCTTCCAGGGGGA

AACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGA TTTTTGTGATGCTCGTCA

GGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCC TTTTGCTGGCCTTTTG

CTCACATGT pAAV-CMV-sadCas9-U6gRNA(Npyr2-sa sgRNA3) used in in vitro qPCR experiments (SEQ ID NO: 116)

CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCGTCGGGCGACC TTTGGTCGCCCGGCC

TCAGTGAGCGAGCGAGCGCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCC TGCGGCCTCTAGACTC

GAGGCGTTGACATTGATTATTGACTAGTTATTAATAGTAATCAATTACGGGGTCATT AGTTCATAGCCCATATATG

GAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGAC CCCCGCCCATTGACGT

CAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAAT GGGTGGAGTATTTACGGT

AAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTG ACGTCAATGACGGTAAAT

GGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGT ACATCTACGTATTAGTCA

TCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAATGGGCGTGGATAGCGGT TTGACTCACGGGGATTT

CCAAGTCTCCACCCCATTGACGTCAATGGGAGTTTGTTTTGGCACCAAAATCAACGG GACTTTCCAAAATGTCGT

AACAACTCCGCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTAT ATAAGCAGAGCTCTCT

GGCTAACTACCGGTGCCACCATGGCCCCAAAGAAGAAGCGGAAGGTCGGTATCCACG GAGTCCCAGCAGCCAA

GCGGAACTACATCCTGGGCCTGGCCATCGGCATCACCAGCGTGGGCTACGGCATCAT CGACTACGAGACACGG

GACGTGATCGATGCCGGCGTGCGGCTGTTCAAAGAGGCCAACGTGGAAAACAACGAG GGCAGGCGGAGCAAG

AGAGGCGCCAGAAGGCTGAAGCGGCGGAGGCGGCATAGAATCCAGAGAGTGAAGAAG CTGCTGTTCGACTAC

AACCTGCTGACCGACCACAGCGAGCTGAGCGGCATCAACCCCTACGAGGCCAGAGTG AAGGGCCTGAGCCAG

AAGCTGAGCGAGGAAGAGTTCTCTGCCGCCCTGCTGCACCTGGCCAAGAGAAGAGGC GTGCACAACGTGAACG

AGGTGGAAGAGGACACCGGCAACGAGCTGTCCACCAAAGAGCAGATCAGCCGGAACA GCAAGGCCCTGGAAG

AGAAATACGTGGCCGAACTGCAGCTGGAACGGCTGAAGAAAGACGGCGAAGTGCGGG GCAGCATCAACAGATT

CAAGACCAGCGACTACGTGAAAGAAGCCAAACAGCTGCTGAAGGTGCAGAAGGCCTA CCACCAGCTGGACCAG

AGCTTCATCGACACCTACATCGACCTGCTGGAAACCCGGCGGACCTACTATGAGGGA CCTGGCGAGGGCAGCC

CCTTCGGCTGGAAGGACATCAAAGAATGGTACGAGATGCTGATGGGCCACTGCACCT ACTTCCCCGAGGAACT

GCGGAGCGTGAAGTACGCCTACAACGCCGACCTGTACAACGCCCTGAACGACCTGAA CAATCTCGTGATCACC

AGGGACGAGAACGAGAAGCTGGAATATTACGAGAAGTTCCAGATCATCGAGAACGTG TTCAAGCAGAAGAAGAA

GCCCACCCTGAAGCAGATCGCCAAAGAAATCCTCGTGAACGAAGAGGATATTAAGGG CTACAGAGTGACCAGCA

CCGGCAAGCCCGAGTTCACCAACCTGAAGGTGTACCACGACATCAAGGACATTACCG CCCGGAAAGAGATTATT GAGAACGCCGAGCTGCTGGATCAGATTGCCAAGATCCTGACCATCTACCAGAGCAGCGAG GACATCCAGGAAG

AACTGACCAATCTGAACTCCGAGCTGACCCAGGAAGAGATCGAGCAGATCTCTAATC TGAAGGGCTATACCGGC

ACCCACAACCTGAGCCTGAAGGCCATCAACCTGATCCTGGACGAGCTGTGGCACACC AACGACAACCAGATCG

CTATCTTCAACCGGCTGAAGCTGGTGCCCAAGAAGGTGGACCTGTCCCAGCAGAAAG AGATCCCCACCACCCT

GGTGGACGACTTCATCCTGAGCCCCGTCGTGAAGAGAAGCTTCATCCAGAGCATCAA AGTGATCAACGCCATCA

TCAAGAAGTACGGCCTGCCCAACGACATCATTATCGAGCTGGCCCGCGAGAAGAACT CCAAGGACGCCCAGAA

AATGATCAACGAGATGCAGAAGCGGAACCGGCAGACCAACGAGCGGATCGAGGAAAT CATCCGGACCACCGGC

AAAGAGAACGCCAAGTACCTGATCGAGAAGATCAAGCTGCACGACATGCAGGAAGGC AAGTGCCTGTACAGCC

TGGAAGCCATCCCTCTGGAAGATCTGCTGAACAACCCCTTCAACTATGAGGTGGACC ACATCATCCCCAGAAGC

GTGTCCTTCGACAACAGCTTCAACAACAAGGTGCTCGTGAAGCAGGAAGAAGCCAGC AAGAAGGGCAACCGGA

CCCCATTCCAGTACCTGAGCAGCAGCGACAGCAAGATCAGCTACGAAACCTTCAAGA AGCACATCCTGAATCTG

GCCAAGGGCAAGGGCAGAATCAGCAAGACCAAGAAAGAGTATCTGCTGGAAGAACGG GACATCAACAGGTTCT

CCGTGCAGAAAGACTTCATCAACCGGAACCTGGTGGATACCAGATACGCCACCAGAG GCCTGATGAACCTGCT

GCGGAGCTACTTCAGAGTGAACAACCTGGACGTGAAAGTGAAGTCCATCAATGGCGG CTTCACCAGCTTTCTGC

GGCGGAAGTGGAAGTTTAAGAAAGAGCGGAACAAGGGGTACAAGCACCACGCCGAGG ACGCCCTGATCATTGC

CAACGCCGATTTCATCTTCAAAGAGTGGAAGAAACTGGACAAGGCCAAAAAAGTGAT GGAAAACCAGATGTTCG

AGGAAAAGCAGGCCGAGAGCATGCCCGAGATCGAAACCGAGCAGGAGTACAAAGAGA TCTTCATCACCCCCCA

CCAGATCAAGCACATTAAGGACTTCAAGGACTACAAGTACAGCCACCGGGTGGACAA GAAGCCTAATAGAGAGC

TGATTAACGACACCCTGTACTCCACCCGGAAGGACGACAAGGGCAACACCCTGATCG TGAACAATCTGAACGGC

CTGTACGACAAGGACAATGACAAGCTGAAAAAGCTGATCAACAAGAGCCCCGAAAAG CTGCTGATGTACCACCA

CGACCCCCAGACCTACCAGAAACTGAAGCTGATTATGGAACAGTACGGCGACGAGAA GAATCCCCTGTACAAGT

ACTACGAGGAAACCGGGAACTACCTGACCAAGTACTCCAAAAAGGACAACGGCCCCG TGATCAAGAAGATTAAG

TATTACGGCAACAAACTGAACGCCCATCTGGACATCACCGACGACTACCCCAACAGC AGAAACAAGGTCGTGAA

GCTGTCCCTGAAGCCCTACAGATTCGACGTGTACCTGGACAATGGCGTGTACAAGTT CGTGACCGTGAAGAATC

TGGATGTGATCAAAAAAGAAAACTACTACGAAGTGAATAGCAAGTGCTATGAGGAAG CTAAGAAGCTGAAGAAGA

TCAGCAACCAGGCCGAGTTTATCGCCTCCTTCTACAACAACGATCTGATCAAGATCA ACGGCGAGCTGTATAGA

GTGATCGGCGTGAACAACGACCTGCTGAACCGGATCGAAGTGAACATGATCGACATC ACCTACCGCGAGTACCT

GGAAAACATGAACGACAAGAGGCCCCCCAGGATCATTAAGACAATCGCCTCCAAGAC CCAGAGCATTAAGAAGT

ACAGCACAGACATTCTGGGCAACCTGTATGAAGTGAAATCTAAGAAGCACCCTCAGA TCATCAAAAAGGGCAAAA

GGCCGGCGGCCACGAAAAAGGCCGGCCAGGCAAAAAAGAAAAAGGGATCCGGACGGG CTGACGCATTGGACG

ATTTTGATCTGGATATGCTGGGAAGTGACGCCCTCGATGATTTTGACCTTGACATGC TTGGTTCGGATGCCCTTG

ATGACTTTGACCTCGACATGCTCGGCAGTGACGCCCTTGATGATTTCGACCTGGACA TGCTGATTAACTGTACAG

GCAGTGGAGAGGGCAGAGGAAGTCTGCTAACATGCGGTGACGTCGAGGAGAATCCTG GCCCAATGGCCAAGC

CTTTGTCTCAAGAAGAATCCACCCTCATTGAAAGAGCAACGGCTACAATCAACAGCA TCCCCATCTCTGAAGACT

ACAGCGTCGCCAGCGCAGCTCTCTCTAGCGACGGCCGCATCTTCACTGGTGTCAATG TATATCATTTTACTGGG

GGACCTTGTGCAGAACTCGTGGTGCTGGGCACTGCTGCTGCTGCGGCAGCTGGCAAC CTGACTTGTATCGTCG

CGATCGGAAATGAGAACAGGGGCATCTTGAGCCCCTGCGGACGGTGCCGACAGGTGC TTCTCGATCTGCATCC

TGGGATCAAAGCCATAGTGAAGGACAGTGATGGACAGCCGACGGCAGTTGGGATTCG TGAATTGCTGCCCTCT

GGTTATGTGTGGGAGGGCTAAGAATTCCTAGAGCTCGCTGATCAGCCTCGACTGTGC CTTCTAGTTGCCAGCCA

TCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACT GTCCTTTCCTAATAAAAT

GAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTG GGGCAGGACAGCAAGG

GGGAGGATTGGGAAGAGAATAGCAGGCATGCTGGGGAGGTACCGAGGGCCTATTTCC CATGATTCCTTCATATT

TGCATATACGATACAAGGCTGTTAGAGAGATAATTGGAATTAATTTGACTGTAAACA CAAAGATATTAGTACAAAA

TACGTGACGTAGAAAGTAATAATTTCTTGGGTAGTTTGCAGTTTTAAAATTATGTTT TAAAATGGACTATCATATGC

TTACCGTAACTTGAAAGTATTTCGATTTCTTGGCTTTATATATCTTGTGGAAAGGAC GAAAcaccGGAGGAGGATC

GGAGATAGAAgTTTTAGTACTCTGGAAACAGAATCTACTAAAACAAGGCAAAATGCC GTGTTTATCTCGTCAACTT

GTTGGCGAGATTTTTGCGGCCGCAGGAACCCCTAGTGATGGAGTTGGCCACTCCCTC TCTGCGCGCTCGCTCG

CTCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGGGCTTTGCCCGGGCGGCC TCAGTGAGCGAGCG

AGCGCGCAGCTGCCTGCAGGGGCGCCTGATGCGGTATTTTCTCCTTACGCATCTGTG CGGTATTTCACACCGCA

TACGTCAAAGCAACCATAGTACGCGCCCTGTAGCGGCGCATTAAGCGCGGCGGGTGT GGTGGTTACGCGCAGC

GTGACCGCTACACTTGCCAGCGCCTTAGCGCCCGCTCCTTTCGCTTTCTTCCCTTCC TTTCTCGCCACGTTCGC

CGGCTTTCCCCGTCAAGCTCTAAATCGGGGGCTCCCTTTAGGGTTCCGATTTAGTGC TTTACGGCACCTCGACC

CCAAAAAACTTGATTTGGGTGATGGTTCACGTAGTGGGCCATCGCCCTGATAGACGG TTTTTCGCCCTTTGACGT TGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAACTGGAACAACACTCAACTCTA TCTCGGGCTATTCTTT

TGATTTATAAGGGATTTTGCCGATTTCGGTCTATTGGTTAAAAAATGAGCTGATTTA ACAAAAATTTAACGCGAATT

TTAACAAAATATTAACGTTTACAATTTTATGGTGCACTCTCAGTACAATCTGCTCTG ATGCCGCATAGTTAAGCCA

GCCCCGACACCCGCCAACACCCGCTGACGCGCCCTGACGGGCTTGTCTGCTCCCGGC ATCCGCTTACAGACAA

GCTGTGACCGTCTCCGGGAGCTGCATGTGTCAGAGGTTTTCACCGTCATCACCGAAA CGCGCGAGACGAAAGG

GCCTCGTGATACGCCTATTTTTATAGGTTAATGTCATGATAATAATGGTTTCTTAGA CGTCAGGTGGCACTTTTCG

GGGAAATGTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTA TCCGCTCATGAGACAATAA

CCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTC CGTGTCGCCCTTATTCCCT

TTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAA AAGATGCTGAAGATCAGTT

GGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAG TTTTCGCCCCGAAGAAC

GTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTA TTGACGCCGGGCAAGAGC

AACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCA CAGAAAAGCATCTTACGG

ATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTG CGGCCAACTTACTTCTGA

CAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATG TAACTCGCCTTGATCGT

TGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCT GTAGCAATGGCAACAA

CGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAA TAGACTGGATGGAGGCG

GATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCT GATAAATCTGGAGCCGG

TGAGCGTGGAAGCCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCG TATCGTAGTTATCTACA

CGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTG CCTCACTGATTAAGCAT

TGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCAT TTTTAATTTAAAAGGATCTAG

GTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTC CACTGAGCGTCAGACCCC

GTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGC TTGCAAACAAAAAAACCAC

CGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGG TAACTGGCTTCAGCAGA

GCGCAGATACCAAATACTGTTCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAG AACTCTGTAGCACCGCCT

ACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCG TGTCTTACCGGGTTGGA

CTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTG CACACAGCCCAGCTTG

GAGCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCC ACGCTTCCCGAAGGGA

GAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGG AGCTTCCAGGGGGA

AACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGA TTTTTGTGATGCTCGTCA

GGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCC TTTTGCTGGCCTTTTG

CTCACATGT

1.11 KCNJ2

Nucleotide sequence of sasgRNA for mouse KCNJ2; sgRNA1 (SEQ ID NO: 117)

TCCTCCTCCTGATGGCGGTTC

Nucleotide sequence of sasgRNA for mouse KCNJ2; sgRNA2 (SEQ ID NO: 118)

GCCCCGGGAACCGCCATCAGG

Nucleotide sequence of sasgRNA for mouse KCNJ2; sgRNA3 (SEQ ID NO: 119)

CAGAGCCAGGGTCCGCGGGTG pAAV-CMV-sadCas9-U6gRNA(Kcnj2-sa sgRNA1) used in in vitro qPCR experiments (SEQ ID NO: 120)

CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCGTCGGGCGACC TTTGGTCGCCCGGCC

TCAGTGAGCGAGCGAGCGCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCC TGCGGCCTCTAGACTC

GAGGCGTTGACATTGATTATTGACTAGTTATTAATAGTAATCAATTACGGGGTCATT AGTTCATAGCCCATATATG

GAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGAC CCCCGCCCATTGACGT

CAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAAT GGGTGGAGTATTTACGGT

AAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTG ACGTCAATGACGGTAAAT

GGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGT ACATCTACGTATTAGTCA

TCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAATGGGCGTGGATAGCGGT TTGACTCACGGGGATTT CCAAGTCTCCACCCCATTGACGTCAATGGGAGTTTGTTTTGGCACCAAAATCAACGGGAC TTTCCAAAATGTCGT

AACAACTCCGCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTAT ATAAGCAGAGCTCTCT

GGCTAACTACCGGTGCCACCATGGCCCCAAAGAAGAAGCGGAAGGTCGGTATCCACG GAGTCCCAGCAGCCAA

GCGGAACTACATCCTGGGCCTGGCCATCGGCATCACCAGCGTGGGCTACGGCATCAT CGACTACGAGACACGG

GACGTGATCGATGCCGGCGTGCGGCTGTTCAAAGAGGCCAACGTGGAAAACAACGAG GGCAGGCGGAGCAAG

AGAGGCGCCAGAAGGCTGAAGCGGCGGAGGCGGCATAGAATCCAGAGAGTGAAGAAG CTGCTGTTCGACTAC

AACCTGCTGACCGACCACAGCGAGCTGAGCGGCATCAACCCCTACGAGGCCAGAGTG AAGGGCCTGAGCCAG

AAGCTGAGCGAGGAAGAGTTCTCTGCCGCCCTGCTGCACCTGGCCAAGAGAAGAGGC GTGCACAACGTGAACG

AGGTGGAAGAGGACACCGGCAACGAGCTGTCCACCAAAGAGCAGATCAGCCGGAACA GCAAGGCCCTGGAAG

AGAAATACGTGGCCGAACTGCAGCTGGAACGGCTGAAGAAAGACGGCGAAGTGCGGG GCAGCATCAACAGATT

CAAGACCAGCGACTACGTGAAAGAAGCCAAACAGCTGCTGAAGGTGCAGAAGGCCTA CCACCAGCTGGACCAG

AGCTTCATCGACACCTACATCGACCTGCTGGAAACCCGGCGGACCTACTATGAGGGA CCTGGCGAGGGCAGCC

CCTTCGGCTGGAAGGACATCAAAGAATGGTACGAGATGCTGATGGGCCACTGCACCT ACTTCCCCGAGGAACT

GCGGAGCGTGAAGTACGCCTACAACGCCGACCTGTACAACGCCCTGAACGACCTGAA CAATCTCGTGATCACC

AGGGACGAGAACGAGAAGCTGGAATATTACGAGAAGTTCCAGATCATCGAGAACGTG TTCAAGCAGAAGAAGAA

GCCCACCCTGAAGCAGATCGCCAAAGAAATCCTCGTGAACGAAGAGGATATTAAGGG CTACAGAGTGACCAGCA

CCGGCAAGCCCGAGTTCACCAACCTGAAGGTGTACCACGACATCAAGGACATTACCG CCCGGAAAGAGATTATT

GAGAACGCCGAGCTGCTGGATCAGATTGCCAAGATCCTGACCATCTACCAGAGCAGC GAGGACATCCAGGAAG

AACTGACCAATCTGAACTCCGAGCTGACCCAGGAAGAGATCGAGCAGATCTCTAATC TGAAGGGCTATACCGGC

ACCCACAACCTGAGCCTGAAGGCCATCAACCTGATCCTGGACGAGCTGTGGCACACC AACGACAACCAGATCG

CTATCTTCAACCGGCTGAAGCTGGTGCCCAAGAAGGTGGACCTGTCCCAGCAGAAAG AGATCCCCACCACCCT

GGTGGACGACTTCATCCTGAGCCCCGTCGTGAAGAGAAGCTTCATCCAGAGCATCAA AGTGATCAACGCCATCA

TCAAGAAGTACGGCCTGCCCAACGACATCATTATCGAGCTGGCCCGCGAGAAGAACT CCAAGGACGCCCAGAA

AATGATCAACGAGATGCAGAAGCGGAACCGGCAGACCAACGAGCGGATCGAGGAAAT CATCCGGACCACCGGC

AAAGAGAACGCCAAGTACCTGATCGAGAAGATCAAGCTGCACGACATGCAGGAAGGC AAGTGCCTGTACAGCC

TGGAAGCCATCCCTCTGGAAGATCTGCTGAACAACCCCTTCAACTATGAGGTGGACC ACATCATCCCCAGAAGC

GTGTCCTTCGACAACAGCTTCAACAACAAGGTGCTCGTGAAGCAGGAAGAAGCCAGC AAGAAGGGCAACCGGA

CCCCATTCCAGTACCTGAGCAGCAGCGACAGCAAGATCAGCTACGAAACCTTCAAGA AGCACATCCTGAATCTG

GCCAAGGGCAAGGGCAGAATCAGCAAGACCAAGAAAGAGTATCTGCTGGAAGAACGG GACATCAACAGGTTCT

CCGTGCAGAAAGACTTCATCAACCGGAACCTGGTGGATACCAGATACGCCACCAGAG GCCTGATGAACCTGCT

GCGGAGCTACTTCAGAGTGAACAACCTGGACGTGAAAGTGAAGTCCATCAATGGCGG CTTCACCAGCTTTCTGC

GGCGGAAGTGGAAGTTTAAGAAAGAGCGGAACAAGGGGTACAAGCACCACGCCGAGG ACGCCCTGATCATTGC

CAACGCCGATTTCATCTTCAAAGAGTGGAAGAAACTGGACAAGGCCAAAAAAGTGAT GGAAAACCAGATGTTCG

AGGAAAAGCAGGCCGAGAGCATGCCCGAGATCGAAACCGAGCAGGAGTACAAAGAGA TCTTCATCACCCCCCA

CCAGATCAAGCACATTAAGGACTTCAAGGACTACAAGTACAGCCACCGGGTGGACAA GAAGCCTAATAGAGAGC

TGATTAACGACACCCTGTACTCCACCCGGAAGGACGACAAGGGCAACACCCTGATCG TGAACAATCTGAACGGC

CTGTACGACAAGGACAATGACAAGCTGAAAAAGCTGATCAACAAGAGCCCCGAAAAG CTGCTGATGTACCACCA

CGACCCCCAGACCTACCAGAAACTGAAGCTGATTATGGAACAGTACGGCGACGAGAA GAATCCCCTGTACAAGT

ACTACGAGGAAACCGGGAACTACCTGACCAAGTACTCCAAAAAGGACAACGGCCCCG TGATCAAGAAGATTAAG

TATTACGGCAACAAACTGAACGCCCATCTGGACATCACCGACGACTACCCCAACAGC AGAAACAAGGTCGTGAA

GCTGTCCCTGAAGCCCTACAGATTCGACGTGTACCTGGACAATGGCGTGTACAAGTT CGTGACCGTGAAGAATC

TGGATGTGATCAAAAAAGAAAACTACTACGAAGTGAATAGCAAGTGCTATGAGGAAG CTAAGAAGCTGAAGAAGA

TCAGCAACCAGGCCGAGTTTATCGCCTCCTTCTACAACAACGATCTGATCAAGATCA ACGGCGAGCTGTATAGA

GTGATCGGCGTGAACAACGACCTGCTGAACCGGATCGAAGTGAACATGATCGACATC ACCTACCGCGAGTACCT

GGAAAACATGAACGACAAGAGGCCCCCCAGGATCATTAAGACAATCGCCTCCAAGAC CCAGAGCATTAAGAAGT

ACAGCACAGACATTCTGGGCAACCTGTATGAAGTGAAATCTAAGAAGCACCCTCAGA TCATCAAAAAGGGCAAAA

GGCCGGCGGCCACGAAAAAGGCCGGCCAGGCAAAAAAGAAAAAGGGATCCGGACGGG CTGACGCATTGGACG

ATTTTGATCTGGATATGCTGGGAAGTGACGCCCTCGATGATTTTGACCTTGACATGC TTGGTTCGGATGCCCTTG

ATGACTTTGACCTCGACATGCTCGGCAGTGACGCCCTTGATGATTTCGACCTGGACA TGCTGATTAACTGTACAG

GCAGTGGAGAGGGCAGAGGAAGTCTGCTAACATGCGGTGACGTCGAGGAGAATCCTG GCCCAATGGCCAAGC

CTTTGTCTCAAGAAGAATCCACCCTCATTGAAAGAGCAACGGCTACAATCAACAGCA TCCCCATCTCTGAAGACT

ACAGCGTCGCCAGCGCAGCTCTCTCTAGCGACGGCCGCATCTTCACTGGTGTCAATG TATATCATTTTACTGGG

GGACCTTGTGCAGAACTCGTGGTGCTGGGCACTGCTGCTGCTGCGGCAGCTGGCAAC CTGACTTGTATCGTCG CGATCGGAAATGAGAACAGGGGCATCTTGAGCCCCTGCGGACGGTGCCGACAGGTGCTTC TCGATCTGCATCC

TGGGATCAAAGCCATAGTGAAGGACAGTGATGGACAGCCGACGGCAGTTGGGATTCG TGAATTGCTGCCCTCT

GGTTATGTGTGGGAGGGCTAAGAATTCCTAGAGCTCGCTGATCAGCCTCGACTGTGC CTTCTAGTTGCCAGCCA

TCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACT GTCCTTTCCTAATAAAAT

GAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTG GGGCAGGACAGCAAGG

GGGAGGATTGGGAAGAGAATAGCAGGCATGCTGGGGAGGTACCGAGGGCCTATTTCC CATGATTCCTTCATATT

TGCATATACGATACAAGGCTGTTAGAGAGATAATTGGAATTAATTTGACTGTAAACA CAAAGATATTAGTACAAAA

TACGTGACGTAGAAAGTAATAATTTCTTGGGTAGTTTGCAGTTTTAAAATTATGTTT TAAAATGGACTATCATATGC

TTACCGTAACTTGAAAGTATTTCGATTTCTTGGCTTTATATATCTTGTGGAAAGGAC GAAAcaccTCCTCCTCCTGA

TGGCGGTTCgTTTTAGTACTCTGGAAACAGAATCTACTAAAACAAGGCAAAATGCCG TGTTTATCTCGTCAACTTG

TTGGCGAGATTTTTGCGGCCGCAGGAACCCCTAGTGATGGAGTTGGCCACTCCCTCT CTGCGCGCTCGCTCGC

TCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGGGCTTTGCCCGGGCGGCCT CAGTGAGCGAGCGA

GCGCGCAGCTGCCTGCAGGGGCGCCTGATGCGGTATTTTCTCCTTACGCATCTGTGC GGTATTTCACACCGCAT

ACGTCAAAGCAACCATAGTACGCGCCCTGTAGCGGCGCATTAAGCGCGGCGGGTGTG GTGGTTACGCGCAGC

GTGACCGCTACACTTGCCAGCGCCTTAGCGCCCGCTCCTTTCGCTTTCTTCCCTTCC TTTCTCGCCACGTTCGC

CGGCTTTCCCCGTCAAGCTCTAAATCGGGGGCTCCCTTTAGGGTTCCGATTTAGTGC TTTACGGCACCTCGACC

CCAAAAAACTTGATTTGGGTGATGGTTCACGTAGTGGGCCATCGCCCTGATAGACGG TTTTTCGCCCTTTGACGT

TGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAACTGGAACAACACTCAACT CTATCTCGGGCTATTCTTT

TGATTTATAAGGGATTTTGCCGATTTCGGTCTATTGGTTAAAAAATGAGCTGATTTA ACAAAAATTTAACGCGAATT

TTAACAAAATATTAACGTTTACAATTTTATGGTGCACTCTCAGTACAATCTGCTCTG ATGCCGCATAGTTAAGCCA

GCCCCGACACCCGCCAACACCCGCTGACGCGCCCTGACGGGCTTGTCTGCTCCCGGC ATCCGCTTACAGACAA

GCTGTGACCGTCTCCGGGAGCTGCATGTGTCAGAGGTTTTCACCGTCATCACCGAAA CGCGCGAGACGAAAGG

GCCTCGTGATACGCCTATTTTTATAGGTTAATGTCATGATAATAATGGTTTCTTAGA CGTCAGGTGGCACTTTTCG

GGGAAATGTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTA TCCGCTCATGAGACAATAA

CCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTC CGTGTCGCCCTTATTCCCT

TTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAA AAGATGCTGAAGATCAGTT

GGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAG TTTTCGCCCCGAAGAAC

GTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTA TTGACGCCGGGCAAGAGC

AACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCA CAGAAAAGCATCTTACGG

ATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTG CGGCCAACTTACTTCTGA

CAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATG TAACTCGCCTTGATCGT

TGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCT GTAGCAATGGCAACAA

CGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAA TAGACTGGATGGAGGCG

GATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCT GATAAATCTGGAGCCGG

TGAGCGTGGAAGCCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCG TATCGTAGTTATCTACA

CGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTG CCTCACTGATTAAGCAT

TGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCAT TTTTAATTTAAAAGGATCTAG

GTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTC CACTGAGCGTCAGACCCC

GTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGC TTGCAAACAAAAAAACCAC

CGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGG TAACTGGCTTCAGCAGA

GCGCAGATACCAAATACTGTTCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAG AACTCTGTAGCACCGCCT

ACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCG TGTCTTACCGGGTTGGA

CTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTG CACACAGCCCAGCTTG

GAGCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCC ACGCTTCCCGAAGGGA

GAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGG AGCTTCCAGGGGGA

AACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGA TTTTTGTGATGCTCGTCA

GGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCC TTTTGCTGGCCTTTTG

CTCACATGT pAAV-CMV-sadCas9-U6gRNA(Kcnj2-sa sgRNA2) used in in vitro qPCR experiments (SEQ ID NO: 121)

CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCGTCGGGCGACC TTTGGTCGCCCGGCC

TCAGTGAGCGAGCGAGCGCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCC TGCGGCCTCTAGACTC

GAGGCGTTGACATTGATTATTGACTAGTTATTAATAGTAATCAATTACGGGGTCATT AGTTCATAGCCCATATATG GAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCC CGCCCATTGACGT

CAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAAT GGGTGGAGTATTTACGGT

AAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTG ACGTCAATGACGGTAAAT

GGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGT ACATCTACGTATTAGTCA

TCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAATGGGCGTGGATAGCGGT TTGACTCACGGGGATTT

CCAAGTCTCCACCCCATTGACGTCAATGGGAGTTTGTTTTGGCACCAAAATCAACGG GACTTTCCAAAATGTCGT

AACAACTCCGCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTAT ATAAGCAGAGCTCTCT

GGCTAACTACCGGTGCCACCATGGCCCCAAAGAAGAAGCGGAAGGTCGGTATCCACG GAGTCCCAGCAGCCAA

GCGGAACTACATCCTGGGCCTGGCCATCGGCATCACCAGCGTGGGCTACGGCATCAT CGACTACGAGACACGG

GACGTGATCGATGCCGGCGTGCGGCTGTTCAAAGAGGCCAACGTGGAAAACAACGAG GGCAGGCGGAGCAAG

AGAGGCGCCAGAAGGCTGAAGCGGCGGAGGCGGCATAGAATCCAGAGAGTGAAGAAG CTGCTGTTCGACTAC

AACCTGCTGACCGACCACAGCGAGCTGAGCGGCATCAACCCCTACGAGGCCAGAGTG AAGGGCCTGAGCCAG

AAGCTGAGCGAGGAAGAGTTCTCTGCCGCCCTGCTGCACCTGGCCAAGAGAAGAGGC GTGCACAACGTGAACG

AGGTGGAAGAGGACACCGGCAACGAGCTGTCCACCAAAGAGCAGATCAGCCGGAACA GCAAGGCCCTGGAAG

AGAAATACGTGGCCGAACTGCAGCTGGAACGGCTGAAGAAAGACGGCGAAGTGCGGG GCAGCATCAACAGATT

CAAGACCAGCGACTACGTGAAAGAAGCCAAACAGCTGCTGAAGGTGCAGAAGGCCTA CCACCAGCTGGACCAG

AGCTTCATCGACACCTACATCGACCTGCTGGAAACCCGGCGGACCTACTATGAGGGA CCTGGCGAGGGCAGCC

CCTTCGGCTGGAAGGACATCAAAGAATGGTACGAGATGCTGATGGGCCACTGCACCT ACTTCCCCGAGGAACT

GCGGAGCGTGAAGTACGCCTACAACGCCGACCTGTACAACGCCCTGAACGACCTGAA CAATCTCGTGATCACC

AGGGACGAGAACGAGAAGCTGGAATATTACGAGAAGTTCCAGATCATCGAGAACGTG TTCAAGCAGAAGAAGAA

GCCCACCCTGAAGCAGATCGCCAAAGAAATCCTCGTGAACGAAGAGGATATTAAGGG CTACAGAGTGACCAGCA

CCGGCAAGCCCGAGTTCACCAACCTGAAGGTGTACCACGACATCAAGGACATTACCG CCCGGAAAGAGATTATT

GAGAACGCCGAGCTGCTGGATCAGATTGCCAAGATCCTGACCATCTACCAGAGCAGC GAGGACATCCAGGAAG

AACTGACCAATCTGAACTCCGAGCTGACCCAGGAAGAGATCGAGCAGATCTCTAATC TGAAGGGCTATACCGGC

ACCCACAACCTGAGCCTGAAGGCCATCAACCTGATCCTGGACGAGCTGTGGCACACC AACGACAACCAGATCG

CTATCTTCAACCGGCTGAAGCTGGTGCCCAAGAAGGTGGACCTGTCCCAGCAGAAAG AGATCCCCACCACCCT

GGTGGACGACTTCATCCTGAGCCCCGTCGTGAAGAGAAGCTTCATCCAGAGCATCAA AGTGATCAACGCCATCA

TCAAGAAGTACGGCCTGCCCAACGACATCATTATCGAGCTGGCCCGCGAGAAGAACT CCAAGGACGCCCAGAA

AATGATCAACGAGATGCAGAAGCGGAACCGGCAGACCAACGAGCGGATCGAGGAAAT CATCCGGACCACCGGC

AAAGAGAACGCCAAGTACCTGATCGAGAAGATCAAGCTGCACGACATGCAGGAAGGC AAGTGCCTGTACAGCC

TGGAAGCCATCCCTCTGGAAGATCTGCTGAACAACCCCTTCAACTATGAGGTGGACC ACATCATCCCCAGAAGC

GTGTCCTTCGACAACAGCTTCAACAACAAGGTGCTCGTGAAGCAGGAAGAAGCCAGC AAGAAGGGCAACCGGA

CCCCATTCCAGTACCTGAGCAGCAGCGACAGCAAGATCAGCTACGAAACCTTCAAGA AGCACATCCTGAATCTG

GCCAAGGGCAAGGGCAGAATCAGCAAGACCAAGAAAGAGTATCTGCTGGAAGAACGG GACATCAACAGGTTCT

CCGTGCAGAAAGACTTCATCAACCGGAACCTGGTGGATACCAGATACGCCACCAGAG GCCTGATGAACCTGCT

GCGGAGCTACTTCAGAGTGAACAACCTGGACGTGAAAGTGAAGTCCATCAATGGCGG CTTCACCAGCTTTCTGC

GGCGGAAGTGGAAGTTTAAGAAAGAGCGGAACAAGGGGTACAAGCACCACGCCGAGG ACGCCCTGATCATTGC

CAACGCCGATTTCATCTTCAAAGAGTGGAAGAAACTGGACAAGGCCAAAAAAGTGAT GGAAAACCAGATGTTCG

AGGAAAAGCAGGCCGAGAGCATGCCCGAGATCGAAACCGAGCAGGAGTACAAAGAGA TCTTCATCACCCCCCA

CCAGATCAAGCACATTAAGGACTTCAAGGACTACAAGTACAGCCACCGGGTGGACAA GAAGCCTAATAGAGAGC

TGATTAACGACACCCTGTACTCCACCCGGAAGGACGACAAGGGCAACACCCTGATCG TGAACAATCTGAACGGC

CTGTACGACAAGGACAATGACAAGCTGAAAAAGCTGATCAACAAGAGCCCCGAAAAG CTGCTGATGTACCACCA

CGACCCCCAGACCTACCAGAAACTGAAGCTGATTATGGAACAGTACGGCGACGAGAA GAATCCCCTGTACAAGT

ACTACGAGGAAACCGGGAACTACCTGACCAAGTACTCCAAAAAGGACAACGGCCCCG TGATCAAGAAGATTAAG

TATTACGGCAACAAACTGAACGCCCATCTGGACATCACCGACGACTACCCCAACAGC AGAAACAAGGTCGTGAA

GCTGTCCCTGAAGCCCTACAGATTCGACGTGTACCTGGACAATGGCGTGTACAAGTT CGTGACCGTGAAGAATC

TGGATGTGATCAAAAAAGAAAACTACTACGAAGTGAATAGCAAGTGCTATGAGGAAG CTAAGAAGCTGAAGAAGA

TCAGCAACCAGGCCGAGTTTATCGCCTCCTTCTACAACAACGATCTGATCAAGATCA ACGGCGAGCTGTATAGA

GTGATCGGCGTGAACAACGACCTGCTGAACCGGATCGAAGTGAACATGATCGACATC ACCTACCGCGAGTACCT

GGAAAACATGAACGACAAGAGGCCCCCCAGGATCATTAAGACAATCGCCTCCAAGAC CCAGAGCATTAAGAAGT

ACAGCACAGACATTCTGGGCAACCTGTATGAAGTGAAATCTAAGAAGCACCCTCAGA TCATCAAAAAGGGCAAAA

GGCCGGCGGCCACGAAAAAGGCCGGCCAGGCAAAAAAGAAAAAGGGATCCGGACGGG CTGACGCATTGGACG

ATTTTGATCTGGATATGCTGGGAAGTGACGCCCTCGATGATTTTGACCTTGACATGC TTGGTTCGGATGCCCTTG ATGACTTTGACCTCGACATGCTCGGCAGTGACGCCCTTGATGATTTCGACCTGGACATGC TGATTAACTGTACAG

GCAGTGGAGAGGGCAGAGGAAGTCTGCTAACATGCGGTGACGTCGAGGAGAATCCTG GCCCAATGGCCAAGC

CTTTGTCTCAAGAAGAATCCACCCTCATTGAAAGAGCAACGGCTACAATCAACAGCA TCCCCATCTCTGAAGACT

ACAGCGTCGCCAGCGCAGCTCTCTCTAGCGACGGCCGCATCTTCACTGGTGTCAATG TATATCATTTTACTGGG

GGACCTTGTGCAGAACTCGTGGTGCTGGGCACTGCTGCTGCTGCGGCAGCTGGCAAC CTGACTTGTATCGTCG

CGATCGGAAATGAGAACAGGGGCATCTTGAGCCCCTGCGGACGGTGCCGACAGGTGC TTCTCGATCTGCATCC

TGGGATCAAAGCCATAGTGAAGGACAGTGATGGACAGCCGACGGCAGTTGGGATTCG TGAATTGCTGCCCTCT

GGTTATGTGTGGGAGGGCTAAGAATTCCTAGAGCTCGCTGATCAGCCTCGACTGTGC CTTCTAGTTGCCAGCCA

TCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACT GTCCTTTCCTAATAAAAT

GAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTG GGGCAGGACAGCAAGG

GGGAGGATTGGGAAGAGAATAGCAGGCATGCTGGGGAGGTACCGAGGGCCTATTTCC CATGATTCCTTCATATT

TGCATATACGATACAAGGCTGTTAGAGAGATAATTGGAATTAATTTGACTGTAAACA CAAAGATATTAGTACAAAA

TACGTGACGTAGAAAGTAATAATTTCTTGGGTAGTTTGCAGTTTTAAAATTATGTTT TAAAATGGACTATCATATGC

TTACCGTAACTTGAAAGTATTTCGATTTCTTGGCTTTATATATCTTGTGGAAAGGAC GAAAcaccGCCCCGGGAAC

CGCCATCAGGgTTTTAGTACTCTGGAAACAGAATCTACTAAAACAAGGCAAAATGCC GTGTTTATCTCGTCAACTT

GTTGGCGAGATTTTTGCGGCCGCAGGAACCCCTAGTGATGGAGTTGGCCACTCCCTC TCTGCGCGCTCGCTCG

CTCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGGGCTTTGCCCGGGCGGCC TCAGTGAGCGAGCG

AGCGCGCAGCTGCCTGCAGGGGCGCCTGATGCGGTATTTTCTCCTTACGCATCTGTG CGGTATTTCACACCGCA

TACGTCAAAGCAACCATAGTACGCGCCCTGTAGCGGCGCATTAAGCGCGGCGGGTGT GGTGGTTACGCGCAGC

GTGACCGCTACACTTGCCAGCGCCTTAGCGCCCGCTCCTTTCGCTTTCTTCCCTTCC TTTCTCGCCACGTTCGC

CGGCTTTCCCCGTCAAGCTCTAAATCGGGGGCTCCCTTTAGGGTTCCGATTTAGTGC TTTACGGCACCTCGACC

CCAAAAAACTTGATTTGGGTGATGGTTCACGTAGTGGGCCATCGCCCTGATAGACGG TTTTTCGCCCTTTGACGT

TGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAACTGGAACAACACTCAACT CTATCTCGGGCTATTCTTT

TGATTTATAAGGGATTTTGCCGATTTCGGTCTATTGGTTAAAAAATGAGCTGATTTA ACAAAAATTTAACGCGAATT

TTAACAAAATATTAACGTTTACAATTTTATGGTGCACTCTCAGTACAATCTGCTCTG ATGCCGCATAGTTAAGCCA

GCCCCGACACCCGCCAACACCCGCTGACGCGCCCTGACGGGCTTGTCTGCTCCCGGC ATCCGCTTACAGACAA

GCTGTGACCGTCTCCGGGAGCTGCATGTGTCAGAGGTTTTCACCGTCATCACCGAAA CGCGCGAGACGAAAGG

GCCTCGTGATACGCCTATTTTTATAGGTTAATGTCATGATAATAATGGTTTCTTAGA CGTCAGGTGGCACTTTTCG

GGGAAATGTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTA TCCGCTCATGAGACAATAA

CCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTC CGTGTCGCCCTTATTCCCT

TTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAA AAGATGCTGAAGATCAGTT

GGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAG TTTTCGCCCCGAAGAAC

GTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTA TTGACGCCGGGCAAGAGC

AACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCA CAGAAAAGCATCTTACGG

ATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTG CGGCCAACTTACTTCTGA

CAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATG TAACTCGCCTTGATCGT

TGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCT GTAGCAATGGCAACAA

CGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAA TAGACTGGATGGAGGCG

GATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCT GATAAATCTGGAGCCGG

TGAGCGTGGAAGCCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCG TATCGTAGTTATCTACA

CGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTG CCTCACTGATTAAGCAT

TGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCAT TTTTAATTTAAAAGGATCTAG

GTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTC CACTGAGCGTCAGACCCC

GTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGC TTGCAAACAAAAAAACCAC

CGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGG TAACTGGCTTCAGCAGA

GCGCAGATACCAAATACTGTTCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAG AACTCTGTAGCACCGCCT

ACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCG TGTCTTACCGGGTTGGA

CTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTG CACACAGCCCAGCTTG

GAGCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCC ACGCTTCCCGAAGGGA

GAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGG AGCTTCCAGGGGGA

AACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGA TTTTTGTGATGCTCGTCA

GGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCC TTTTGCTGGCCTTTTG

CTCACATGT pAAV-CMV-sadCas9-U6gRNA(Kcnj2-sa sgRNA3) used in in vitro qPCR experiments (SEQ ID NO: 122)

CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCGTCGGGCGACC TTTGGTCGCCCGGCC

TCAGTGAGCGAGCGAGCGCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCC TGCGGCCTCTAGACTC

GAGGCGTTGACATTGATTATTGACTAGTTATTAATAGTAATCAATTACGGGGTCATT AGTTCATAGCCCATATATG

GAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGAC CCCCGCCCATTGACGT

CAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAAT GGGTGGAGTATTTACGGT

AAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTG ACGTCAATGACGGTAAAT

GGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGT ACATCTACGTATTAGTCA

TCGCTATTACCATGGTGATGCGGTTTTGGCAGTACATCAATGGGCGTGGATAGCGGT TTGACTCACGGGGATTT

CCAAGTCTCCACCCCATTGACGTCAATGGGAGTTTGTTTTGGCACCAAAATCAACGG GACTTTCCAAAATGTCGT

AACAACTCCGCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTAT ATAAGCAGAGCTCTCT

GGCTAACTACCGGTGCCACCATGGCCCCAAAGAAGAAGCGGAAGGTCGGTATCCACG GAGTCCCAGCAGCCAA

GCGGAACTACATCCTGGGCCTGGCCATCGGCATCACCAGCGTGGGCTACGGCATCAT CGACTACGAGACACGG

GACGTGATCGATGCCGGCGTGCGGCTGTTCAAAGAGGCCAACGTGGAAAACAACGAG GGCAGGCGGAGCAAG

AGAGGCGCCAGAAGGCTGAAGCGGCGGAGGCGGCATAGAATCCAGAGAGTGAAGAAG CTGCTGTTCGACTAC

AACCTGCTGACCGACCACAGCGAGCTGAGCGGCATCAACCCCTACGAGGCCAGAGTG AAGGGCCTGAGCCAG

AAGCTGAGCGAGGAAGAGTTCTCTGCCGCCCTGCTGCACCTGGCCAAGAGAAGAGGC GTGCACAACGTGAACG

AGGTGGAAGAGGACACCGGCAACGAGCTGTCCACCAAAGAGCAGATCAGCCGGAACA GCAAGGCCCTGGAAG

AGAAATACGTGGCCGAACTGCAGCTGGAACGGCTGAAGAAAGACGGCGAAGTGCGGG GCAGCATCAACAGATT

CAAGACCAGCGACTACGTGAAAGAAGCCAAACAGCTGCTGAAGGTGCAGAAGGCCTA CCACCAGCTGGACCAG

AGCTTCATCGACACCTACATCGACCTGCTGGAAACCCGGCGGACCTACTATGAGGGA CCTGGCGAGGGCAGCC

CCTTCGGCTGGAAGGACATCAAAGAATGGTACGAGATGCTGATGGGCCACTGCACCT ACTTCCCCGAGGAACT

GCGGAGCGTGAAGTACGCCTACAACGCCGACCTGTACAACGCCCTGAACGACCTGAA CAATCTCGTGATCACC

AGGGACGAGAACGAGAAGCTGGAATATTACGAGAAGTTCCAGATCATCGAGAACGTG TTCAAGCAGAAGAAGAA

GCCCACCCTGAAGCAGATCGCCAAAGAAATCCTCGTGAACGAAGAGGATATTAAGGG CTACAGAGTGACCAGCA

CCGGCAAGCCCGAGTTCACCAACCTGAAGGTGTACCACGACATCAAGGACATTACCG CCCGGAAAGAGATTATT

GAGAACGCCGAGCTGCTGGATCAGATTGCCAAGATCCTGACCATCTACCAGAGCAGC GAGGACATCCAGGAAG

AACTGACCAATCTGAACTCCGAGCTGACCCAGGAAGAGATCGAGCAGATCTCTAATC TGAAGGGCTATACCGGC

ACCCACAACCTGAGCCTGAAGGCCATCAACCTGATCCTGGACGAGCTGTGGCACACC AACGACAACCAGATCG

CTATCTTCAACCGGCTGAAGCTGGTGCCCAAGAAGGTGGACCTGTCCCAGCAGAAAG AGATCCCCACCACCCT

GGTGGACGACTTCATCCTGAGCCCCGTCGTGAAGAGAAGCTTCATCCAGAGCATCAA AGTGATCAACGCCATCA

TCAAGAAGTACGGCCTGCCCAACGACATCATTATCGAGCTGGCCCGCGAGAAGAACT CCAAGGACGCCCAGAA

AATGATCAACGAGATGCAGAAGCGGAACCGGCAGACCAACGAGCGGATCGAGGAAAT CATCCGGACCACCGGC

AAAGAGAACGCCAAGTACCTGATCGAGAAGATCAAGCTGCACGACATGCAGGAAGGC AAGTGCCTGTACAGCC

TGGAAGCCATCCCTCTGGAAGATCTGCTGAACAACCCCTTCAACTATGAGGTGGACC ACATCATCCCCAGAAGC

GTGTCCTTCGACAACAGCTTCAACAACAAGGTGCTCGTGAAGCAGGAAGAAGCCAGC AAGAAGGGCAACCGGA

CCCCATTCCAGTACCTGAGCAGCAGCGACAGCAAGATCAGCTACGAAACCTTCAAGA AGCACATCCTGAATCTG

GCCAAGGGCAAGGGCAGAATCAGCAAGACCAAGAAAGAGTATCTGCTGGAAGAACGG GACATCAACAGGTTCT

CCGTGCAGAAAGACTTCATCAACCGGAACCTGGTGGATACCAGATACGCCACCAGAG GCCTGATGAACCTGCT

GCGGAGCTACTTCAGAGTGAACAACCTGGACGTGAAAGTGAAGTCCATCAATGGCGG CTTCACCAGCTTTCTGC

GGCGGAAGTGGAAGTTTAAGAAAGAGCGGAACAAGGGGTACAAGCACCACGCCGAGG ACGCCCTGATCATTGC

CAACGCCGATTTCATCTTCAAAGAGTGGAAGAAACTGGACAAGGCCAAAAAAGTGAT GGAAAACCAGATGTTCG

AGGAAAAGCAGGCCGAGAGCATGCCCGAGATCGAAACCGAGCAGGAGTACAAAGAGA TCTTCATCACCCCCCA

CCAGATCAAGCACATTAAGGACTTCAAGGACTACAAGTACAGCCACCGGGTGGACAA GAAGCCTAATAGAGAGC

TGATTAACGACACCCTGTACTCCACCCGGAAGGACGACAAGGGCAACACCCTGATCG TGAACAATCTGAACGGC

CTGTACGACAAGGACAATGACAAGCTGAAAAAGCTGATCAACAAGAGCCCCGAAAAG CTGCTGATGTACCACCA

CGACCCCCAGACCTACCAGAAACTGAAGCTGATTATGGAACAGTACGGCGACGAGAA GAATCCCCTGTACAAGT

ACTACGAGGAAACCGGGAACTACCTGACCAAGTACTCCAAAAAGGACAACGGCCCCG TGATCAAGAAGATTAAG

TATTACGGCAACAAACTGAACGCCCATCTGGACATCACCGACGACTACCCCAACAGC AGAAACAAGGTCGTGAA

GCTGTCCCTGAAGCCCTACAGATTCGACGTGTACCTGGACAATGGCGTGTACAAGTT CGTGACCGTGAAGAATC

TGGATGTGATCAAAAAAGAAAACTACTACGAAGTGAATAGCAAGTGCTATGAGGAAG CTAAGAAGCTGAAGAAGA

TCAGCAACCAGGCCGAGTTTATCGCCTCCTTCTACAACAACGATCTGATCAAGATCA ACGGCGAGCTGTATAGA

GTGATCGGCGTGAACAACGACCTGCTGAACCGGATCGAAGTGAACATGATCGACATC ACCTACCGCGAGTACCT GGAAAACATGAACGACAAGAGGCCCCCCAGGATCATTAAGACAATCGCCTCCAAGACCCA GAGCATTAAGAAGT

ACAGCACAGACATTCTGGGCAACCTGTATGAAGTGAAATCTAAGAAGCACCCTCAGA TCATCAAAAAGGGCAAAA

GGCCGGCGGCCACGAAAAAGGCCGGCCAGGCAAAAAAGAAAAAGGGATCCGGACGGG CTGACGCATTGGACG

ATTTTGATCTGGATATGCTGGGAAGTGACGCCCTCGATGATTTTGACCTTGACATGC TTGGTTCGGATGCCCTTG

ATGACTTTGACCTCGACATGCTCGGCAGTGACGCCCTTGATGATTTCGACCTGGACA TGCTGATTAACTGTACAG

GCAGTGGAGAGGGCAGAGGAAGTCTGCTAACATGCGGTGACGTCGAGGAGAATCCTG GCCCAATGGCCAAGC

CTTTGTCTCAAGAAGAATCCACCCTCATTGAAAGAGCAACGGCTACAATCAACAGCA TCCCCATCTCTGAAGACT

ACAGCGTCGCCAGCGCAGCTCTCTCTAGCGACGGCCGCATCTTCACTGGTGTCAATG TATATCATTTTACTGGG

GGACCTTGTGCAGAACTCGTGGTGCTGGGCACTGCTGCTGCTGCGGCAGCTGGCAAC CTGACTTGTATCGTCG

CGATCGGAAATGAGAACAGGGGCATCTTGAGCCCCTGCGGACGGTGCCGACAGGTGC TTCTCGATCTGCATCC

TGGGATCAAAGCCATAGTGAAGGACAGTGATGGACAGCCGACGGCAGTTGGGATTCG TGAATTGCTGCCCTCT

GGTTATGTGTGGGAGGGCTAAGAATTCCTAGAGCTCGCTGATCAGCCTCGACTGTGC CTTCTAGTTGCCAGCCA

TCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACT GTCCTTTCCTAATAAAAT

GAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTG GGGCAGGACAGCAAGG

GGGAGGATTGGGAAGAGAATAGCAGGCATGCTGGGGAGGTACCGAGGGCCTATTTCC CATGATTCCTTCATATT

TGCATATACGATACAAGGCTGTTAGAGAGATAATTGGAATTAATTTGACTGTAAACA CAAAGATATTAGTACAAAA

TACGTGACGTAGAAAGTAATAATTTCTTGGGTAGTTTGCAGTTTTAAAATTATGTTT TAAAATGGACTATCATATGC

TTACCGTAACTTGAAAGTATTTCGATTTCTTGGCTTTATATATCTTGTGGAAAGGAC GAAAcaccCAGAGCCAGGGT

CCGCGGGTGgTTTTAGTACTCTGGAAACAGAATCTACTAAAACAAGGCAAAATGCCG TGTTTATCTCGTCAACTT

GTTGGCGAGATTTTTGCGGCCGCAGGAACCCCTAGTGATGGAGTTGGCCACTCCCTC TCTGCGCGCTCGCTCG

CTCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGGGCTTTGCCCGGGCGGCC TCAGTGAGCGAGCG

AGCGCGCAGCTGCCTGCAGGGGCGCCTGATGCGGTATTTTCTCCTTACGCATCTGTG CGGTATTTCACACCGCA

TACGTCAAAGCAACCATAGTACGCGCCCTGTAGCGGCGCATTAAGCGCGGCGGGTGT GGTGGTTACGCGCAGC

GTGACCGCTACACTTGCCAGCGCCTTAGCGCCCGCTCCTTTCGCTTTCTTCCCTTCC TTTCTCGCCACGTTCGC

CGGCTTTCCCCGTCAAGCTCTAAATCGGGGGCTCCCTTTAGGGTTCCGATTTAGTGC TTTACGGCACCTCGACC

CCAAAAAACTTGATTTGGGTGATGGTTCACGTAGTGGGCCATCGCCCTGATAGACGG TTTTTCGCCCTTTGACGT

TGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAACTGGAACAACACTCAACT CTATCTCGGGCTATTCTTT

TGATTTATAAGGGATTTTGCCGATTTCGGTCTATTGGTTAAAAAATGAGCTGATTTA ACAAAAATTTAACGCGAATT

TTAACAAAATATTAACGTTTACAATTTTATGGTGCACTCTCAGTACAATCTGCTCTG ATGCCGCATAGTTAAGCCA

GCCCCGACACCCGCCAACACCCGCTGACGCGCCCTGACGGGCTTGTCTGCTCCCGGC ATCCGCTTACAGACAA

GCTGTGACCGTCTCCGGGAGCTGCATGTGTCAGAGGTTTTCACCGTCATCACCGAAA CGCGCGAGACGAAAGG

GCCTCGTGATACGCCTATTTTTATAGGTTAATGTCATGATAATAATGGTTTCTTAGA CGTCAGGTGGCACTTTTCG

GGGAAATGTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTA TCCGCTCATGAGACAATAA

CCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTC CGTGTCGCCCTTATTCCCT

TTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAA AAGATGCTGAAGATCAGTT

GGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAG TTTTCGCCCCGAAGAAC

GTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTA TTGACGCCGGGCAAGAGC

AACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCA CAGAAAAGCATCTTACGG

ATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTG CGGCCAACTTACTTCTGA

CAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATG TAACTCGCCTTGATCGT

TGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCT GTAGCAATGGCAACAA

CGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAA TAGACTGGATGGAGGCG

GATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCT GATAAATCTGGAGCCGG

TGAGCGTGGAAGCCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCG TATCGTAGTTATCTACA

CGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTG CCTCACTGATTAAGCAT

TGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCAT TTTTAATTTAAAAGGATCTAG

GTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTC CACTGAGCGTCAGACCCC

GTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGC TTGCAAACAAAAAAACCAC

CGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGG TAACTGGCTTCAGCAGA

GCGCAGATACCAAATACTGTTCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAG AACTCTGTAGCACCGCCT

ACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCG TGTCTTACCGGGTTGGA

CTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTG CACACAGCCCAGCTTG

GAGCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCC ACGCTTCCCGAAGGGA GAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGGAGC TTCCAGGGGGA

AACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGA TTTTTGTGATGCTCGTCA

GGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCC TTTTGCTGGCCTTTTG CTCACATGT

2. Sequences for in vitro screening using multielectrode arrays (MEA)- EPILEPSY pAAV-U6gRNA(LacZ-sa sgRNA)-shCaMKII-sadCas9-VP64 used as control in in vitro experiments (SEQ ID NO: 123) (the sequence for shCaMKII is represented by "[XXX]") cctgcaggcagctgcgcgctcgctcgctcactgaggccgcccgggcaaagcccgggcgtc gggcgacctttggtcgcccggcctcagtgagcgagcgagcgcg cagagagggagtggccaactccatcactaggggttcctgcggccgcacgcgtggtaccga gggcctatttcccatgattccttcatatttgcatatacgatacaaggct gttagagagataattggaattaatttgactgtaaacacaaagatattagtacaaaatacg tgacgtagaaagtaataatttcttgggtagtttgcagttttaaaattatgtttt aaaatggactatcatatgcttaccgtaacttgaaagtatttcgatttcttggctttatat atcttgtggaaaggacgaaacaccgTGCGAATACGCCCACGCG ATgtttttagtactctggaaacagaatctactaaaacaaggcaaaatgccgtgtttatct cgtcaacttgttggcgagatttttgcgacgcgtAATTccacggggttAA TCGAA[XXX]gatatcgAATTCGGTACCACCGGTgccaccatggccccaaagaagaagcg gaaggtcggtatccacggagtcccagcagccaa gcggaactacatcctgggcctggccatcggcatcaccagcgtgggctacggcatcatcga ctacgagacacgggacgtgatcgatgccggcgtgcggctgttcaa agaggccaacgtggaaaacaacgagggcaggcggagcaagagaggcgccagaaggctgaa gcggcggaggcggcatagaatccagagagtgaagaag ctgctgttcgactacaacctgctgaccgaccacagcgagctgagcggcatcaacccctac gaggccagagtgaagggcctgagccagaagctgagcgaggaag agttctctgccgccctgctgcacctggccaagagaagaggcgtgcacaacgtgaacgagg tggaagaggacaccggcaacgagctgtccaccaaagagcaga tcagccggaacagcaaggccctggaagagaaatacgtggccgaactgcagctggaacggc tgaagaaagacggcgaagtgcggggcagcatcaacagattc aagaccagcgactacgtgaaagaagccaaacagctgctgaaggtgcagaaggcctaccac cagctggaccagagcttcatcgacacctacatcgacctgctgg aaacccggcggacctactatgagggacctggcgagggcagccccttcggctggaaggaca tcaaagaatggtacgagatgctgatgggccactgcacctacttc cccgaggaactgcggagcgtgaagtacgcctacaacgccgacctgtacaacgccctgaac gacctgaacaatctcgtgatcaccagggacgagaacgagaag ctggaatattacgagaagttccagatcatcgagaacgtgttcaagcagaagaagaagccc accctgaagcagatcgccaaagaaatcctcgtgaacgaagagg atattaagggctacagagtgaccagcaccggcaagcccgagttcaccaacctgaaggtgt accacgacatcaaggacattaccgcccggaaagagattattgag aacgccgagctgctggatcagattgccaagatcctgaccatctaccagagcagcgaggac atccaggaagaactgaccaatctgaactccgagctgacccagga agagatcgagcagatctctaatctgaagggctataccggcacccacaacctgagcctgaa ggccatcaacctgatcctggacgagctgtggcacaccaacgaca accagatcgctatcttcaaccggctgaagctggtgcccaagaaggtggacctgtcccagc agaaagagatccccaccaccctggtggacgacttcatcctgagccc cgtcgtgaagagaagcttcatccagagcatcaaagtgatcaacgccatcatcaagaagta cggcctgcccaacgacatcattatcgagctggcccgcgagaaga actccaaggacgcccagaaaatgatcaacgagatgcagaagcggaaccggcagaccaacg agcggatcgaggaaatcatccggaccaccggcaaagaga acgccaagtacctgatcgagaagatcaagctgcacgacatgcaggaaggcaagtgcctgt acagcctggaagccatccctctggaagatctgctgaacaacccct tcaactatgaggtggaccacatcatccccagaagcgtgtccttcgacaacagcttcaaca acaaggtgctcgtgaagcaggaagaagccagcaagaagggcaa ccggaccccattccagtacctgagcagcagcgacagcaagatcagctacgaaaccttcaa gaagcacatcctgaatctggccaagggcaagggcagaatcagc aagaccaagaaagagtatctgctggaagaacgggacatcaacaggttctccgtgcagaaa gacttcatcaaccggaacctggtggataccagatacgccaccag aggcctgatgaacctgctgcggagctacttcagagtgaacaacctggacgtgaaagtgaa gtccatcaatggcggcttcaccagctttctgcggcggaagtggaag tttaagaaagagcggaacaaggggtacaagcaccacgccgaggacgccctgatcattgcc aacgccgatttcatcttcaaagagtggaagaaactggacaagg ccaaaaaagtgatggaaaaccagatgttcgaggaaaagcaggccgagagcatgcccgaga tcgaaaccgagcaggagtacaaagagatcttcatcacccccc accagatcaagcacattaaggacttcaaggactacaagtacagccaccgggtggacaaga agcctaatagagagctgattaacgacaccctgtactccacccgg aaggacgacaagggcaacaccctgatcgtgaacaatctgaacggcctgtacgacaaggac aatgacaagctgaaaaagctgatcaacaagagccccgaaaa gctgctgatgtaccaccacgacccccagacctaccagaaactgaagctgattatggaaca gtacggcgacgagaagaatcccctgtacaagtactacgaggaaa ccgggaactacctgaccaagtactccaaaaaggacaacggccccgtgatcaagaagatta agtattacggcaacaaactgaacgcccatctggacatcaccgac gactaccccaacagcagaaacaaggtcgtgaagctgtccctgaagccctacagattcgac gtgtacctggacaatggcgtgtacaagttcgtgaccgtgaagaatc tggatgtgatcaaaaaagaaaactactacgaagtgaatagcaagtgctatgaggaagcta agaagctgaagaagatcagcaaccaggccgagtttatcgcctcct tctacaacaacgatctgatcaagatcaacggcgagctgtatagagtgatcggcgtgaaca acgacctgctgaaccggatcgaagtgaacatgatcgacatcaccta ccgcgagtacctggaaaacatgaacgacaagaggccccccaggatcattaagacaatcgc ctccaagacccagagcattaagaagtacagcacagacattctg ggcaacctgtatgaagtgaaatctaagaagcaccctcagatcatcaaaaagggcaaaagg ccggcggccacgaaaaaggccggccaggcaaaaaagaaaa agggatccgaggccagcggttccggacgggctgacgcattggacgattttgatctggata tgctgggaagtgacgccctcgatgattttgaccttgacatgcttggttcg gatgcccttgatgactttgacctcgacatgctcggcagtgacgcccttgatgatttcgac ctggacatgctgattaactcaagatgatctagacatatggatatctgactag tctcgagtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcac aaataaagcatttttttcactggaccgagcggccgcaggaacccctagtg atggagttggccactccctctctgcgcgctcgctcgctcactgaggccgggcgaccaaag gtcgcccgacgcccgggctttgcccgggcggcctcagtgagcgag cgagcgcgcagctgcctgcaggggcgcctgatgcggtattttctccttacgcatctgtgc ggtatttcacaccgcatacgtcaaagcaaccatagtacgcgccctgtag cggcgcattaagcgcggcgggtgtggtggttacgcgcagcgtgaccgctacacttgccag cgccctagcgcccgctcctttcgctttcttcccttcctttctcgccacgttc gccggctttccccgtcaagctctaaatcgggggctccctttagggttccgatttagtgct ttacggcacctcgaccccaaaaaacttgatttgggtgatggttcacgtagtg ggccatcgccctgatagacggtttttcgccctttgacgttggagtccacgttctttaata gtggactcttgttccaaactggaacaacactcaaccctatctcgggctattcttt tgatttataagggattttgccgatttcggcctattggttaaaaaatgagctgatttaaca aaaatttaacgcgaattttaacaaaatattaacgtttacaattttatggtgcact ctcagtacaatctgctctgatgccgcatagttaagccagccccgacacccgccaacaccc gctgacgcgccctgacgggcttgtctgctcccggcatccgcttacag acaagctgtgaccgtctccgggagctgcatgtgtcagaggttttcaccgtcatcaccgaa acgcgcgagacgaaagggcctcgtgatacgcctatttttataggttaat gtcatgataataatggtttcttagacgtcaggtggcacttttcggggaaatgtgcgcgga acccctatttgtttatttttctaaatacattcaaatatgtatccgctcatgagac aataaccctgataaatgcttcaataatattgaaaaaggaagagtatgagtattcaacatt tccgtgtcgcccttattcccttttttgcggcattttgccttcctgtttttgctcacc cagaaacgctggtgaaagtaaaagatgctgaagatcagttgggtgcacgagtgggttaca tcgaactggatctcaacagcggtaagatccttgagagttttcgcccc gaagaacgttttccaatgatgagcacttttaaagttctgctatgtggcgcggtattatcc cgtattgacgccgggcaagagcaactcggtcgccgcatacactattctcag aatgacttggttgagtactcaccagtcacagaaaagcatcttacggatggcatgacagta agagaattatgcagtgctgccataaccatgagtgataacactgcggc caacttacttctgacaacgatcggaggaccgaaggagctaaccgcttttttgcacaacat gggggatcatgtaactcgccttgatcgttgggaaccggagctgaatga agccataccaaacgacgagcgtgacaccacgatgcctgtagcaatggcaacaacgttgcg caaactattaactggcgaactacttactctagcttcccggcaacaa ttaatagactggatggaggcggataaagttgcaggaccacttctgcgctcggcccttccg gctggctggtttattgctgataaatctggagccggtgagcgtgggtctcg cggtatcattgcagcactggggccagatggtaagccctcccgtatcgtagttatctacac gacggggagtcaggcaactatggatgaacgaaatagacagatcgct gagataggtgcctcactgattaagcattggtaactgtcagaccaagtttactcatatata ctttagattgatttaaaacttcatttttaatttaaaaggatctaggtgaagatcc tttttgataatctcatgaccaaaatcccttaacgtgagttttcgttccactgagcgtcag accccgtagaaaagatcaaaggatcttcttgagatcctttttttctgcgcgtaat ctgctgcttgcaaacaaaaaaaccaccgctaccagcggtggtttgtttgccggatcaaga gctaccaactctttttccgaaggtaactggcttcagcagagcgcagat accaaatactgtccttctagtgtagccgtagttaggccaccacttcaagaactctgtagc accgcctacatacctcgctctgctaatcctgttaccagtggctgctgccagt ggcgataagtcgtgtcttaccgggttggactcaagacgatagttaccggataaggcgcag cggtcgggctgaacggggggttcgtgcacacagcccagcttggag cgaacgacctacaccgaactgagatacctacagcgtgagctatgagaaagcgccacgctt cccgaagggagaaaggcggacaggtatccggtaagcggcagg gtcggaacaggagagcgcacgagggagcttccagggggaaacgcctggtatctttatagt cctgtcgggtttcgccacctctgacttgagcgtcgatttttgtgatgctc gtcaggggggcggagcctatggaaaaacgccagcaacgcggcctttttacggttcctggc cttttgctggccttttgctcacatgt pAAV-U6gRNA(Kcna2-sa sgRNA2)-shCaMKII-sadCas9-VP64 used in in vitro experiments (SEQ ID NO: 124) (the sequence for shCaMKII is represented by "[XXX]") cctgcaggcagctgcgcgctcgctcgctcactgaggccgcccgggcaaagcccgggcgtc gggcgacctttggtcgcccggcctcagtgagcgagcgagcgcg cagagagggagtggccaactccatcactaggggttcctgcggccgcacgcgtggtaccga gggcctatttcccatgattccttcatatttgcatatacgatacaaggct gttagagagataattggaattaatttgactgtaaacacaaagatattagtacaaaatacg tgacgtagaaagtaataatttcttgggtagtttgcagttttaaaattatgtttt aaaatggactatcatatgcttaccgtaacttgaaagtatttcgatttcttggctttatat atcttgtggaaaggacgaaacaccGCCCCAGCCGGCCCCTTTA ATgttttagtactctggaaacagaatctactaaaacaaggcaaaatgccgtgtttatctc gtcaacttgttggcgagatttttgcgacgcgtAATTccacggggttAAT CGAA[XXX]gatatcgAATTCGGTACCACCGGTgccaccatggccccaaagaagaagcgg aaggtcggtatccacggagtcccagcagccaagc ggaactacatcctgggcctggccatcggcatcaccagcgtgggctacggcatcatcgact acgagacacgggacgtgatcgatgccggcgtgcggctgttcaaag aggccaacgtggaaaacaacgagggcaggcggagcaagagaggcgccagaaggctgaagc ggcggaggcggcatagaatccagagagtgaagaagctg ctgttcgactacaacctgctgaccgaccacagcgagctgagcggcatcaacccctacgag gccagagtgaagggcctgagccagaagctgagcgaggaagag ttctctgccgccctgctgcacctggccaagagaagaggcgtgcacaacgtgaacgaggtg gaagaggacaccggcaacgagctgtccaccaaagagcagatc agccggaacagcaaggccctggaagagaaatacgtggccgaactgcagctggaacggctg aagaaagacggcgaagtgcggggcagcatcaacagattca agaccagcgactacgtgaaagaagccaaacagctgctgaaggtgcagaaggcctaccacc agctggaccagagcttcatcgacacctacatcgacctgctgga aacccggcggacctactatgagggacctggcgagggcagccccttcggctggaaggacat caaagaatggtacgagatgctgatgggccactgcacctacttccc cgaggaactgcggagcgtgaagtacgcctacaacgccgacctgtacaacgccctgaacga cctgaacaatctcgtgatcaccagggacgagaacgagaagct ggaatattacgagaagttccagatcatcgagaacgtgttcaagcagaagaagaagcccac cctgaagcagatcgccaaagaaatcctcgtgaacgaagaggat attaagggctacagagtgaccagcaccggcaagcccgagttcaccaacctgaaggtgtac cacgacatcaaggacattaccgcccggaaagagattattgagaa cgccgagctgctggatcagattgccaagatcctgaccatctaccagagcagcgaggacat ccaggaagaactgaccaatctgaactccgagctgacccaggaag agatcgagcagatctctaatctgaagggctataccggcacccacaacctgagcctgaagg ccatcaacctgatcctggacgagctgtggcacaccaacgacaac cagatcgctatcttcaaccggctgaagctggtgcccaagaaggtggacctgtcccagcag aaagagatccccaccaccctggtggacgacttcatcctgagccccg tcgtgaagagaagcttcatccagagcatcaaagtgatcaacgccatcatcaagaagtacg gcctgcccaacgacatcattatcgagctggcccgcgagaagaact ccaaggacgcccagaaaatgatcaacgagatgcagaagcggaaccggcagaccaacgagc ggatcgaggaaatcatccggaccaccggcaaagagaacg ccaagtacctgatcgagaagatcaagctgcacgacatgcaggaaggcaagtgcctgtaca gcctggaagccatccctctggaagatctgctgaacaaccccttca actatgaggtggaccacatcatccccagaagcgtgtccttcgacaacagcttcaacaaca aggtgctcgtgaagcaggaagaagccagcaagaagggcaaccg gaccccattccagtacctgagcagcagcgacagcaagatcagctacgaaaccttcaagaa gcacatcctgaatctggccaagggcaagggcagaatcagcaa gaccaagaaagagtatctgctggaagaacgggacatcaacaggttctccgtgcagaaaga cttcatcaaccggaacctggtggataccagatacgccaccagag gcctgatgaacctgctgcggagctacttcagagtgaacaacctggacgtgaaagtgaagt ccatcaatggcggcttcaccagctttctgcggcggaagtggaagttt aagaaagagcggaacaaggggtacaagcaccacgccgaggacgccctgatcattgccaac gccgatttcatcttcaaagagtggaagaaactggacaaggcc aaaaaagtgatggaaaaccagatgttcgaggaaaagcaggccgagagcatgcccgagatc gaaaccgagcaggagtacaaagagatcttcatcacccccca ccagatcaagcacattaaggacttcaaggactacaagtacagccaccgggtggacaagaa gcctaatagagagctgattaacgacaccctgtactccacccgga aggacgacaagggcaacaccctgatcgtgaacaatctgaacggcctgtacgacaaggaca atgacaagctgaaaaagctgatcaacaagagccccgaaaag ctgctgatgtaccaccacgacccccagacctaccagaaactgaagctgattatggaacag tacggcgacgagaagaatcccctgtacaagtactacgaggaaac cgggaactacctgaccaagtactccaaaaaggacaacggccccgtgatcaagaagattaa gtattacggcaacaaactgaacgcccatctggacatcaccgac gactaccccaacagcagaaacaaggtcgtgaagctgtccctgaagccctacagattcgac gtgtacctggacaatggcgtgtacaagttcgtgaccgtgaagaatc tggatgtgatcaaaaaagaaaactactacgaagtgaatagcaagtgctatgaggaagcta agaagctgaagaagatcagcaaccaggccgagtttatcgcctcct tctacaacaacgatctgatcaagatcaacggcgagctgtatagagtgatcggcgtgaaca acgacctgctgaaccggatcgaagtgaacatgatcgacatcaccta ccgcgagtacctggaaaacatgaacgacaagaggccccccaggatcattaagacaatcgc ctccaagacccagagcattaagaagtacagcacagacattctg ggcaacctgtatgaagtgaaatctaagaagcaccctcagatcatcaaaaagggcaaaagg ccggcggccacgaaaaaggccggccaggcaaaaaagaaaa agggatccgaggccagcggttccggacgggctgacgcattggacgattttgatctggata tgctgggaagtgacgccctcgatgattttgaccttgacatgcttggttcg gatgcccttgatgactttgacctcgacatgctcggcagtgacgcccttgatgatttcgac ctggacatgctgattaactcaagatgatctagacatatggatatctgactag tctcgagtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcac aaataaagcatttttttcactggaccgagcggccgcaggaacccctagtg atggagttggccactccctctctgcgcgctcgctcgctcactgaggccgggcgaccaaag gtcgcccgacgcccgggctttgcccgggcggcctcagtgagcgag cgagcgcgcagctgcctgcaggggcgcctgatgcggtattttctccttacgcatctgtgc ggtatttcacaccgcatacgtcaaagcaaccatagtacgcgccctgtag cggcgcattaagcgcggcgggtgtggtggttacgcgcagcgtgaccgctacacttgccag cgccctagcgcccgctcctttcgctttcttcccttcctttctcgccacgttc gccggctttccccgtcaagctctaaatcgggggctccctttagggttccgatttagtgct ttacggcacctcgaccccaaaaaacttgatttgggtgatggttcacgtagtg ggccatcgccctgatagacggtttttcgccctttgacgttggagtccacgttctttaata gtggactcttgttccaaactggaacaacactcaaccctatctcgggctattcttt tgatttataagggattttgccgatttcggcctattggttaaaaaatgagctgatttaaca aaaatttaacgcgaattttaacaaaatattaacgtttacaattttatggtgcact ctcagtacaatctgctctgatgccgcatagttaagccagccccgacacccgccaacaccc gctgacgcgccctgacgggcttgtctgctcccggcatccgcttacag acaagctgtgaccgtctccgggagctgcatgtgtcagaggttttcaccgtcatcaccgaa acgcgcgagacgaaagggcctcgtgatacgcctatttttataggttaat gtcatgataataatggtttcttagacgtcaggtggcacttttcggggaaatgtgcgcgga acccctatttgtttatttttctaaatacattcaaatatgtatccgctcatgagac aataaccctgataaatgcttcaataatattgaaaaaggaagagtatgagtattcaacatt tccgtgtcgcccttattcccttttttgcggcattttgccttcctgtttttgctcacc cagaaacgctggtgaaagtaaaagatgctgaagatcagttgggtgcacgagtgggttaca tcgaactggatctcaacagcggtaagatccttgagagttttcgcccc gaagaacgttttccaatgatgagcacttttaaagttctgctatgtggcgcggtattatcc cgtattgacgccgggcaagagcaactcggtcgccgcatacactattctcag aatgacttggttgagtactcaccagtcacagaaaagcatcttacggatggcatgacagta agagaattatgcagtgctgccataaccatgagtgataacactgcggc caacttacttctgacaacgatcggaggaccgaaggagctaaccgcttttttgcacaacat gggggatcatgtaactcgccttgatcgttgggaaccggagctgaatga agccataccaaacgacgagcgtgacaccacgatgcctgtagcaatggcaacaacgttgcg caaactattaactggcgaactacttactctagcttcccggcaacaa ttaatagactggatggaggcggataaagttgcaggaccacttctgcgctcggcccttccg gctggctggtttattgctgataaatctggagccggtgagcgtgggtctcg cggtatcattgcagcactggggccagatggtaagccctcccgtatcgtagttatctacac gacggggagtcaggcaactatggatgaacgaaatagacagatcgct gagataggtgcctcactgattaagcattggtaactgtcagaccaagtttactcatatata ctttagattgatttaaaacttcatttttaatttaaaaggatctaggtgaagatcc tttttgataatctcatgaccaaaatcccttaacgtgagttttcgttccactgagcgtcag accccgtagaaaagatcaaaggatcttcttgagatcctttttttctgcgcgtaat ctgctgcttgcaaacaaaaaaaccaccgctaccagcggtggtttgtttgccggatcaaga gctaccaactctttttccgaaggtaactggcttcagcagagcgcagat accaaatactgtccttctagtgtagccgtagttaggccaccacttcaagaactctgtagc accgcctacatacctcgctctgctaatcctgttaccagtggctgctgccagt ggcgataagtcgtgtcttaccgggttggactcaagacgatagttaccggataaggcgcag cggtcgggctgaacggggggttcgtgcacacagcccagcttggag cgaacgacctacaccgaactgagatacctacagcgtgagctatgagaaagcgccacgctt cccgaagggagaaaggcggacaggtatccggtaagcggcagg gtcggaacaggagagcgcacgagggagcttccagggggaaacgcctggtatctttatagt cctgtcgggtttcgccacctctgacttgagcgtcgatttttgtgatgctc gtcaggggggcggagcctatggaaaaacgccagcaacgcggcctttttacggttcctggc cttttgctggccttttgctcacatgt pAAV-U6gRNA(Lgi1-sa sgRNA2)-shCaMKII-sadCas9-VP64 used in in vitro experiments (SEQ ID NO: 125) (the sequence for shCaMKII is represented by "[XXX]") cctgcaggcagctgcgcgctcgctcgctcactgaggccgcccgggcaaagcccgggcgtc gggcgacctttggtcgcccggcctcagtgagcgagcgagcgcg cagagagggagtggccaactccatcactaggggttcctgcggccgcacgcgtggtaccga gggcctatttcccatgattccttcatatttgcatatacgatacaaggct gttagagagataattggaattaatttgactgtaaacacaaagatattagtacaaaatacg tgacgtagaaagtaataatttcttgggtagtttgcagttttaaaattatgtttt aaaatggactatcatatgcttaccgtaacttgaaagtatttcgatttcttggctttatat atcttgtggaaaggacgaaacaccgCACTGCTGGGGGAAGAGA CCTgttttagtactctggaaacagaatctactaaaacaaggcaaaatgccgtgtttatct cgtcaacttgttggcgagatttttgcgacgcgtAATTccacggggttA ATCGAA[XXX]gatatcgAATTCGGTACCACCGGTgccaccatggccccaaagaagaagc ggaaggtcggtatccacggagtcccagcagcca agcggaactacatcctgggcctggccatcggcatcaccagcgtgggctacggcatcatcg actacgagacacgggacgtgatcgatgccggcgtgcggctgttca aagaggccaacgtggaaaacaacgagggcaggcggagcaagagaggcgccagaaggctga agcggcggaggcggcatagaatccagagagtgaagaa gctgctgttcgactacaacctgctgaccgaccacagcgagctgagcggcatcaaccccta cgaggccagagtgaagggcctgagccagaagctgagcgaggaa gagttctctgccgccctgctgcacctggccaagagaagaggcgtgcacaacgtgaacgag gtggaagaggacaccggcaacgagctgtccaccaaagagcag atcagccggaacagcaaggccctggaagagaaatacgtggccgaactgcagctggaacgg ctgaagaaagacggcgaagtgcggggcagcatcaacagatt caagaccagcgactacgtgaaagaagccaaacagctgctgaaggtgcagaaggcctacca ccagctggaccagagcttcatcgacacctacatcgacctgctg gaaacccggcggacctactatgagggacctggcgagggcagccccttcggctggaaggac atcaaagaatggtacgagatgctgatgggccactgcacctactt ccccgaggaactgcggagcgtgaagtacgcctacaacgccgacctgtacaacgccctgaa cgacctgaacaatctcgtgatcaccagggacgagaacgagaa gctggaatattacgagaagttccagatcatcgagaacgtgttcaagcagaagaagaagcc caccctgaagcagatcgccaaagaaatcctcgtgaacgaagag gatattaagggctacagagtgaccagcaccggcaagcccgagttcaccaacctgaaggtg taccacgacatcaaggacattaccgcccggaaagagattattga gaacgccgagctgctggatcagattgccaagatcctgaccatctaccagagcagcgagga catccaggaagaactgaccaatctgaactccgagctgacccagg aagagatcgagcagatctctaatctgaagggctataccggcacccacaacctgagcctga aggccatcaacctgatcctggacgagctgtggcacaccaacgac aaccagatcgctatcttcaaccggctgaagctggtgcccaagaaggtggacctgtcccag cagaaagagatccccaccaccctggtggacgacttcatcctgagc cccgtcgtgaagagaagcttcatccagagcatcaaagtgatcaacgccatcatcaagaag tacggcctgcccaacgacatcattatcgagctggcccgcgagaag aactccaaggacgcccagaaaatgatcaacgagatgcagaagcggaaccggcagaccaac gagcggatcgaggaaatcatccggaccaccggcaaagag aacgccaagtacctgatcgagaagatcaagctgcacgacatgcaggaaggcaagtgcctg tacagcctggaagccatccctctggaagatctgctgaacaaccc cttcaactatgaggtggaccacatcatccccagaagcgtgtccttcgacaacagcttcaa caacaaggtgctcgtgaagcaggaagaagccagcaagaagggca accggaccccattccagtacctgagcagcagcgacagcaagatcagctacgaaaccttca agaagcacatcctgaatctggccaagggcaagggcagaatcag caagaccaagaaagagtatctgctggaagaacgggacatcaacaggttctccgtgcagaa agacttcatcaaccggaacctggtggataccagatacgccacca gaggcctgatgaacctgctgcggagctacttcagagtgaacaacctggacgtgaaagtga agtccatcaatggcggcttcaccagctttctgcggcggaagtggaa gtttaagaaagagcggaacaaggggtacaagcaccacgccgaggacgccctgatcattgc caacgccgatttcatcttcaaagagtggaagaaactggacaag gccaaaaaagtgatggaaaaccagatgttcgaggaaaagcaggccgagagcatgcccgag atcgaaaccgagcaggagtacaaagagatcttcatcacccc ccaccagatcaagcacattaaggacttcaaggactacaagtacagccaccgggtggacaa gaagcctaatagagagctgattaacgacaccctgtactccaccc ggaaggacgacaagggcaacaccctgatcgtgaacaatctgaacggcctgtacgacaagg acaatgacaagctgaaaaagctgatcaacaagagccccgaa aagctgctgatgtaccaccacgacccccagacctaccagaaactgaagctgattatggaa cagtacggcgacgagaagaatcccctgtacaagtactacgagga aaccgggaactacctgaccaagtactccaaaaaggacaacggccccgtgatcaagaagat taagtattacggcaacaaactgaacgcccatctggacatcacc gacgactaccccaacagcagaaacaaggtcgtgaagctgtccctgaagccctacagattc gacgtgtacctggacaatggcgtgtacaagttcgtgaccgtgaag aatctggatgtgatcaaaaaagaaaactactacgaagtgaatagcaagtgctatgaggaa gctaagaagctgaagaagatcagcaaccaggccgagtttatcgc ctccttctacaacaacgatctgatcaagatcaacggcgagctgtatagagtgatcggcgt gaacaacgacctgctgaaccggatcgaagtgaacatgatcgacatc acctaccgcgagtacctggaaaacatgaacgacaagaggccccccaggatcattaagaca atcgcctccaagacccagagcattaagaagtacagcacagac attctgggcaacctgtatgaagtgaaatctaagaagcaccctcagatcatcaaaaagggc aaaaggccggcggccacgaaaaaggccggccaggcaaaaaa gaaaaagggatccgaggccagcggttccggacgggctgacgcattggacgattttgatct ggatatgctgggaagtgacgccctcgatgattttgaccttgacatgctt ggttcggatgcccttgatgactttgacctcgacatgctcggcagtgacgcccttgatgat ttcgacctggacatgctgattaactcaagatgatctagacatatggatatct gactagtctcgagtttattgcagcttataatggttacaaataaagcaatagcatcacaaa tttcacaaataaagcatttttttcactggaccgagcggccgcaggaaccc ctagtgatggagttggccactccctctctgcgcgctcgctcgctcactgaggccgggcga ccaaaggtcgcccgacgcccgggctttgcccgggcggcctcagtga gcgagcgagcgcgcagctgcctgcaggggcgcctgatgcggtattttctccttacgcatc tgtgcggtatttcacaccgcatacgtcaaagcaaccatagtacgcgcc ctgtagcggcgcattaagcgcggcgggtgtggtggttacgcgcagcgtgaccgctacact tgccagcgccctagcgcccgctcctttcgctttcttcccttcctttctcgcc acgttcgccggctttccccgtcaagctctaaatcgggggctccctttagggttccgattt agtgctttacggcacctcgaccccaaaaaacttgatttgggtgatggttcac gtagtgggccatcgccctgatagacggtttttcgccctttgacgttggagtccacgttct ttaatagtggactcttgttccaaactggaacaacactcaaccctatctcgggc tattcttttgatttataagggattttgccgatttcggcctattggttaaaaaatgagctg atttaacaaaaatttaacgcgaattttaacaaaatattaacgtttacaattttatggt gcactctcagtacaatctgctctgatgccgcatagttaagccagccccgacacccgccaa cacccgctgacgcgccctgacgggcttgtctgctcccggcatccgctt acagacaagctgtgaccgtctccgggagctgcatgtgtcagaggttttcaccgtcatcac cgaaacgcgcgagacgaaagggcctcgtgatacgcctatttttatagg ttaatgtcatgataataatggtttcttagacgtcaggtggcacttttcggggaaatgtgc gcggaacccctatttgtttatttttctaaatacattcaaatatgtatccgctcatg agacaataaccctgataaatgcttcaataatattgaaaaaggaagagtatgagtattcaa catttccgtgtcgcccttattcccttttttgcggcattttgccttcctgtttttgct cacccagaaacgctggtgaaagtaaaagatgctgaagatcagttgggtgcacgagtgggt tacatcgaactggatctcaacagcggtaagatccttgagagttttcg ccccgaagaacgttttccaatgatgagcacttttaaagttctgctatgtggcgcggtatt atcccgtattgacgccgggcaagagcaactcggtcgccgcatacactatt ctcagaatgacttggttgagtactcaccagtcacagaaaagcatcttacggatggcatga cagtaagagaattatgcagtgctgccataaccatgagtgataacactg cggccaacttacttctgacaacgatcggaggaccgaaggagctaaccgcttttttgcaca acatgggggatcatgtaactcgccttgatcgttgggaaccggagctga atgaagccataccaaacgacgagcgtgacaccacgatgcctgtagcaatggcaacaacgt tgcgcaaactattaactggcgaactacttactctagcttcccggca acaattaatagactggatggaggcggataaagttgcaggaccacttctgcgctcggccct tccggctggctggtttattgctgataaatctggagccggtgagcgtggg tctcgcggtatcattgcagcactggggccagatggtaagccctcccgtatcgtagttatc tacacgacggggagtcaggcaactatggatgaacgaaatagacagat cgctgagataggtgcctcactgattaagcattggtaactgtcagaccaagtttactcata tatactttagattgatttaaaacttcatttttaatttaaaaggatctaggtgaag atcctttttgataatctcatgaccaaaatcccttaacgtgagttttcgttccactgagcg tcagaccccgtagaaaagatcaaaggatcttcttgagatcctttttttctgcgcg taatctgctgcttgcaaacaaaaaaaccaccgctaccagcggtggtttgtttgccggatc aagagctaccaactctttttccgaaggtaactggcttcagcagagcgca gataccaaatactgtccttctagtgtagccgtagttaggccaccacttcaagaactctgt agcaccgcctacatacctcgctctgctaatcctgttaccagtggctgctgcc agtggcgataagtcgtgtcttaccgggttggactcaagacgatagttaccggataaggcg cagcggtcgggctgaacggggggttcgtgcacacagcccagcttgg agcgaacgacctacaccgaactgagatacctacagcgtgagctatgagaaagcgccacgc ttcccgaagggagaaaggcggacaggtatccggtaagcggca gggtcggaacaggagagcgcacgagggagcttccagggggaaacgcctggtatctttata gtcctgtcgggtttcgccacctctgacttgagcgtcgatttttgtgatg ctcgtcaggggggcggagcctatggaaaaacgccagcaacgcggcctttttacggttcct ggccttttgctggccttttgctcacatgt pAAV-U6gRNA(Kcnq2-sa sgRNA6)-shCaMKII-sadCas9-VP64 used in in vitro experiments (SEQ ID NO: 126) (the sequence for shCaMKII is represented by "[XXX]") cctgcaggcagctgcgcgctcgctcgctcactgaggccgcccgggcaaagcccgggcgtc gggcgacctttggtcgcccggcctcagtgagcgagcgagcgcg cagagagggagtggccaactccatcactaggggttcctgcggccgcacgcgtggtaccga gggcctatttcccatgattccttcatatttgcatatacgatacaaggct gttagagagataattggaattaatttgactgtaaacacaaagatattagtacaaaatacg tgacgtagaaagtaataatttcttgggtagtttgcagttttaaaattatgtttt aaaatggactatcatatgcttaccgtaacttgaaagtatttcgatttcttggctttatat atcttgtggaaaggacgaaacaccTCCTAGCCCGGTAATCCTT GAgttttagtactctggaaacagaatctactaaaacaaggcaaaatgccgtgtttatctc gtcaacttgttggcgagatttttgcgacgcgtAATTccacggggttAA TCGAA[XXX]gatatcgAATTCGGTACCACCGGTgccaccatggccccaaagaagaagcg gaaggtcggtatccacggagtcccagcagccaa gcggaactacatcctgggcctggccatcggcatcaccagcgtgggctacggcatcatcga ctacgagacacgggacgtgatcgatgccggcgtgcggctgttcaa agaggccaacgtggaaaacaacgagggcaggcggagcaagagaggcgccagaaggctgaa gcggcggaggcggcatagaatccagagagtgaagaag ctgctgttcgactacaacctgctgaccgaccacagcgagctgagcggcatcaacccctac gaggccagagtgaagggcctgagccagaagctgagcgaggaag agttctctgccgccctgctgcacctggccaagagaagaggcgtgcacaacgtgaacgagg tggaagaggacaccggcaacgagctgtccaccaaagagcaga tcagccggaacagcaaggccctggaagagaaatacgtggccgaactgcagctggaacggc tgaagaaagacggcgaagtgcggggcagcatcaacagattc aagaccagcgactacgtgaaagaagccaaacagctgctgaaggtgcagaaggcctaccac cagctggaccagagcttcatcgacacctacatcgacctgctgg aaacccggcggacctactatgagggacctggcgagggcagccccttcggctggaaggaca tcaaagaatggtacgagatgctgatgggccactgcacctacttc cccgaggaactgcggagcgtgaagtacgcctacaacgccgacctgtacaacgccctgaac gacctgaacaatctcgtgatcaccagggacgagaacgagaag ctggaatattacgagaagttccagatcatcgagaacgtgttcaagcagaagaagaagccc accctgaagcagatcgccaaagaaatcctcgtgaacgaagagg atattaagggctacagagtgaccagcaccggcaagcccgagttcaccaacctgaaggtgt accacgacatcaaggacattaccgcccggaaagagattattgag aacgccgagctgctggatcagattgccaagatcctgaccatctaccagagcagcgaggac atccaggaagaactgaccaatctgaactccgagctgacccagga agagatcgagcagatctctaatctgaagggctataccggcacccacaacctgagcctgaa ggccatcaacctgatcctggacgagctgtggcacaccaacgaca accagatcgctatcttcaaccggctgaagctggtgcccaagaaggtggacctgtcccagc agaaagagatccccaccaccctggtggacgacttcatcctgagccc cgtcgtgaagagaagcttcatccagagcatcaaagtgatcaacgccatcatcaagaagta cggcctgcccaacgacatcattatcgagctggcccgcgagaaga actccaaggacgcccagaaaatgatcaacgagatgcagaagcggaaccggcagaccaacg agcggatcgaggaaatcatccggaccaccggcaaagaga acgccaagtacctgatcgagaagatcaagctgcacgacatgcaggaaggcaagtgcctgt acagcctggaagccatccctctggaagatctgctgaacaacccct tcaactatgaggtggaccacatcatccccagaagcgtgtccttcgacaacagcttcaaca acaaggtgctcgtgaagcaggaagaagccagcaagaagggcaa ccggaccccattccagtacctgagcagcagcgacagcaagatcagctacgaaaccttcaa gaagcacatcctgaatctggccaagggcaagggcagaatcagc aagaccaagaaagagtatctgctggaagaacgggacatcaacaggttctccgtgcagaaa gacttcatcaaccggaacctggtggataccagatacgccaccag aggcctgatgaacctgctgcggagctacttcagagtgaacaacctggacgtgaaagtgaa gtccatcaatggcggcttcaccagctttctgcggcggaagtggaag tttaagaaagagcggaacaaggggtacaagcaccacgccgaggacgccctgatcattgcc aacgccgatttcatcttcaaagagtggaagaaactggacaagg ccaaaaaagtgatggaaaaccagatgttcgaggaaaagcaggccgagagcatgcccgaga tcgaaaccgagcaggagtacaaagagatcttcatcacccccc accagatcaagcacattaaggacttcaaggactacaagtacagccaccgggtggacaaga agcctaatagagagctgattaacgacaccctgtactccacccgg aaggacgacaagggcaacaccctgatcgtgaacaatctgaacggcctgtacgacaaggac aatgacaagctgaaaaagctgatcaacaagagccccgaaaa gctgctgatgtaccaccacgacccccagacctaccagaaactgaagctgattatggaaca gtacggcgacgagaagaatcccctgtacaagtactacgaggaaa ccgggaactacctgaccaagtactccaaaaaggacaacggccccgtgatcaagaagatta agtattacggcaacaaactgaacgcccatctggacatcaccgac gactaccccaacagcagaaacaaggtcgtgaagctgtccctgaagccctacagattcgac gtgtacctggacaatggcgtgtacaagttcgtgaccgtgaagaatc tggatgtgatcaaaaaagaaaactactacgaagtgaatagcaagtgctatgaggaagcta agaagctgaagaagatcagcaaccaggccgagtttatcgcctcct tctacaacaacgatctgatcaagatcaacggcgagctgtatagagtgatcggcgtgaaca acgacctgctgaaccggatcgaagtgaacatgatcgacatcaccta ccgcgagtacctggaaaacatgaacgacaagaggccccccaggatcattaagacaatcgc ctccaagacccagagcattaagaagtacagcacagacattctg ggcaacctgtatgaagtgaaatctaagaagcaccctcagatcatcaaaaagggcaaaagg ccggcggccacgaaaaaggccggccaggcaaaaaagaaaa agggatccgaggccagcggttccggacgggctgacgcattggacgattttgatctggata tgctgggaagtgacgccctcgatgattttgaccttgacatgcttggttcg gatgcccttgatgactttgacctcgacatgctcggcagtgacgcccttgatgatttcgac ctggacatgctgattaactcaagatgatctagacatatggatatctgactag tctcgagtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcac aaataaagcatttttttcactggaccgagcggccgcaggaacccctagtg atggagttggccactccctctctgcgcgctcgctcgctcactgaggccgggcgaccaaag gtcgcccgacgcccgggctttgcccgggcggcctcagtgagcgag cgagcgcgcagctgcctgcaggggcgcctgatgcggtattttctccttacgcatctgtgc ggtatttcacaccgcatacgtcaaagcaaccatagtacgcgccctgtag cggcgcattaagcgcggcgggtgtggtggttacgcgcagcgtgaccgctacacttgccag cgccctagcgcccgctcctttcgctttcttcccttcctttctcgccacgttc gccggctttccccgtcaagctctaaatcgggggctccctttagggttccgatttagtgct ttacggcacctcgaccccaaaaaacttgatttgggtgatggttcacgtagtg ggccatcgccctgatagacggtttttcgccctttgacgttggagtccacgttctttaata gtggactcttgttccaaactggaacaacactcaaccctatctcgggctattcttt tgatttataagggattttgccgatttcggcctattggttaaaaaatgagctgatttaaca aaaatttaacgcgaattttaacaaaatattaacgtttacaattttatggtgcact ctcagtacaatctgctctgatgccgcatagttaagccagccccgacacccgccaacaccc gctgacgcgccctgacgggcttgtctgctcccggcatccgcttacag acaagctgtgaccgtctccgggagctgcatgtgtcagaggttttcaccgtcatcaccgaa acgcgcgagacgaaagggcctcgtgatacgcctatttttataggttaat gtcatgataataatggtttcttagacgtcaggtggcacttttcggggaaatgtgcgcgga acccctatttgtttatttttctaaatacattcaaatatgtatccgctcatgagac aataaccctgataaatgcttcaataatattgaaaaaggaagagtatgagtattcaacatt tccgtgtcgcccttattcccttttttgcggcattttgccttcctgtttttgctcacc cagaaacgctggtgaaagtaaaagatgctgaagatcagttgggtgcacgagtgggttaca tcgaactggatctcaacagcggtaagatccttgagagttttcgcccc gaagaacgttttccaatgatgagcacttttaaagttctgctatgtggcgcggtattatcc cgtattgacgccgggcaagagcaactcggtcgccgcatacactattctcag aatgacttggttgagtactcaccagtcacagaaaagcatcttacggatggcatgacagta agagaattatgcagtgctgccataaccatgagtgataacactgcggc caacttacttctgacaacgatcggaggaccgaaggagctaaccgcttttttgcacaacat gggggatcatgtaactcgccttgatcgttgggaaccggagctgaatga agccataccaaacgacgagcgtgacaccacgatgcctgtagcaatggcaacaacgttgcg caaactattaactggcgaactacttactctagcttcccggcaacaa ttaatagactggatggaggcggataaagttgcaggaccacttctgcgctcggcccttccg gctggctggtttattgctgataaatctggagccggtgagcgtgggtctcg cggtatcattgcagcactggggccagatggtaagccctcccgtatcgtagttatctacac gacggggagtcaggcaactatggatgaacgaaatagacagatcgct gagataggtgcctcactgattaagcattggtaactgtcagaccaagtttactcatatata ctttagattgatttaaaacttcatttttaatttaaaaggatctaggtgaagatcc tttttgataatctcatgaccaaaatcccttaacgtgagttttcgttccactgagcgtcag accccgtagaaaagatcaaaggatcttcttgagatcctttttttctgcgcgtaat ctgctgcttgcaaacaaaaaaaccaccgctaccagcggtggtttgtttgccggatcaaga gctaccaactctttttccgaaggtaactggcttcagcagagcgcagat accaaatactgtccttctagtgtagccgtagttaggccaccacttcaagaactctgtagc accgcctacatacctcgctctgctaatcctgttaccagtggctgctgccagt ggcgataagtcgtgtcttaccgggttggactcaagacgatagttaccggataaggcgcag cggtcgggctgaacggggggttcgtgcacacagcccagcttggag cgaacgacctacaccgaactgagatacctacagcgtgagctatgagaaagcgccacgctt cccgaagggagaaaggcggacaggtatccggtaagcggcagg gtcggaacaggagagcgcacgagggagcttccagggggaaacgcctggtatctttatagt cctgtcgggtttcgccacctctgacttgagcgtcgatttttgtgatgctc gtcaggggggcggagcctatggaaaaacgccagcaacgcggcctttttacggttcctggc cttttgctggccttttgctcacatgt pAAV-U6gRNA(Kcnq3-sa sgRNA3)-shCaMKII-sadCas9-VP64 used in in vitro experiments (SEQ ID NO: 127) (the sequence for shCaMKII is represented by "[XXX]") cctgcaggcagctgcgcgctcgctcgctcactgaggccgcccgggcaaagcccgggcgtc gggcgacctttggtcgcccggcctcagtgagcgagcgagcgcg cagagagggagtggccaactccatcactaggggttcctgcggccgcacgcgtggtaccga gggcctatttcccatgattccttcatatttgcatatacgatacaaggct gttagagagataattggaattaatttgactgtaaacacaaagatattagtacaaaatacg tgacgtagaaagtaataatttcttgggtagtttgcagttttaaaattatgtttt aaaatggactatcatatgcttaccgtaacttgaaagtatttcgatttcttggctttatat atcttgtggaaaggacgaaacaccCTACTGCCGCTGCAGCGGG GCgttttagtactctggaaacagaatctactaaaacaaggcaaaatgccgtgtttatctc gtcaacttgttggcgagatttttgcgacgcgtAATTccacggggttAA TCGAA[XXX]gatatcgAATTCGGTACCACCGGTgccaccatggccccaaagaagaagcg gaaggtcggtatccacggagtcccagcagccaa gcggaactacatcctgggcctggccatcggcatcaccagcgtgggctacggcatcatcga ctacgagacacgggacgtgatcgatgccggcgtgcggctgttcaa agaggccaacgtggaaaacaacgagggcaggcggagcaagagaggcgccagaaggctgaa gcggcggaggcggcatagaatccagagagtgaagaag ctgctgttcgactacaacctgctgaccgaccacagcgagctgagcggcatcaacccctac gaggccagagtgaagggcctgagccagaagctgagcgaggaag agttctctgccgccctgctgcacctggccaagagaagaggcgtgcacaacgtgaacgagg tggaagaggacaccggcaacgagctgtccaccaaagagcaga tcagccggaacagcaaggccctggaagagaaatacgtggccgaactgcagctggaacggc tgaagaaagacggcgaagtgcggggcagcatcaacagattc aagaccagcgactacgtgaaagaagccaaacagctgctgaaggtgcagaaggcctaccac cagctggaccagagcttcatcgacacctacatcgacctgctgg aaacccggcggacctactatgagggacctggcgagggcagccccttcggctggaaggaca tcaaagaatggtacgagatgctgatgggccactgcacctacttc cccgaggaactgcggagcgtgaagtacgcctacaacgccgacctgtacaacgccctgaac gacctgaacaatctcgtgatcaccagggacgagaacgagaag ctggaatattacgagaagttccagatcatcgagaacgtgttcaagcagaagaagaagccc accctgaagcagatcgccaaagaaatcctcgtgaacgaagagg atattaagggctacagagtgaccagcaccggcaagcccgagttcaccaacctgaaggtgt accacgacatcaaggacattaccgcccggaaagagattattgag aacgccgagctgctggatcagattgccaagatcctgaccatctaccagagcagcgaggac atccaggaagaactgaccaatctgaactccgagctgacccagga agagatcgagcagatctctaatctgaagggctataccggcacccacaacctgagcctgaa ggccatcaacctgatcctggacgagctgtggcacaccaacgaca accagatcgctatcttcaaccggctgaagctggtgcccaagaaggtggacctgtcccagc agaaagagatccccaccaccctggtggacgacttcatcctgagccc cgtcgtgaagagaagcttcatccagagcatcaaagtgatcaacgccatcatcaagaagta cggcctgcccaacgacatcattatcgagctggcccgcgagaaga actccaaggacgcccagaaaatgatcaacgagatgcagaagcggaaccggcagaccaacg agcggatcgaggaaatcatccggaccaccggcaaagaga acgccaagtacctgatcgagaagatcaagctgcacgacatgcaggaaggcaagtgcctgt acagcctggaagccatccctctggaagatctgctgaacaacccct tcaactatgaggtggaccacatcatccccagaagcgtgtccttcgacaacagcttcaaca acaaggtgctcgtgaagcaggaagaagccagcaagaagggcaa ccggaccccattccagtacctgagcagcagcgacagcaagatcagctacgaaaccttcaa gaagcacatcctgaatctggccaagggcaagggcagaatcagc aagaccaagaaagagtatctgctggaagaacgggacatcaacaggttctccgtgcagaaa gacttcatcaaccggaacctggtggataccagatacgccaccag aggcctgatgaacctgctgcggagctacttcagagtgaacaacctggacgtgaaagtgaa gtccatcaatggcggcttcaccagctttctgcggcggaagtggaag tttaagaaagagcggaacaaggggtacaagcaccacgccgaggacgccctgatcattgcc aacgccgatttcatcttcaaagagtggaagaaactggacaagg ccaaaaaagtgatggaaaaccagatgttcgaggaaaagcaggccgagagcatgcccgaga tcgaaaccgagcaggagtacaaagagatcttcatcacccccc accagatcaagcacattaaggacttcaaggactacaagtacagccaccgggtggacaaga agcctaatagagagctgattaacgacaccctgtactccacccgg aaggacgacaagggcaacaccctgatcgtgaacaatctgaacggcctgtacgacaaggac aatgacaagctgaaaaagctgatcaacaagagccccgaaaa gctgctgatgtaccaccacgacccccagacctaccagaaactgaagctgattatggaaca gtacggcgacgagaagaatcccctgtacaagtactacgaggaaa ccgggaactacctgaccaagtactccaaaaaggacaacggccccgtgatcaagaagatta agtattacggcaacaaactgaacgcccatctggacatcaccgac gactaccccaacagcagaaacaaggtcgtgaagctgtccctgaagccctacagattcgac gtgtacctggacaatggcgtgtacaagttcgtgaccgtgaagaatc tggatgtgatcaaaaaagaaaactactacgaagtgaatagcaagtgctatgaggaagcta agaagctgaagaagatcagcaaccaggccgagtttatcgcctcct tctacaacaacgatctgatcaagatcaacggcgagctgtatagagtgatcggcgtgaaca acgacctgctgaaccggatcgaagtgaacatgatcgacatcaccta ccgcgagtacctggaaaacatgaacgacaagaggccccccaggatcattaagacaatcgc ctccaagacccagagcattaagaagtacagcacagacattctg ggcaacctgtatgaagtgaaatctaagaagcaccctcagatcatcaaaaagggcaaaagg ccggcggccacgaaaaaggccggccaggcaaaaaagaaaa agggatccgaggccagcggttccggacgggctgacgcattggacgattttgatctggata tgctgggaagtgacgccctcgatgattttgaccttgacatgcttggttcg gatgcccttgatgactttgacctcgacatgctcggcagtgacgcccttgatgatttcgac ctggacatgctgattaactcaagatgatctagacatatggatatctgactag tctcgagtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcac aaataaagcatttttttcactggaccgagcggccgcaggaacccctagtg atggagttggccactccctctctgcgcgctcgctcgctcactgaggccgggcgaccaaag gtcgcccgacgcccgggctttgcccgggcggcctcagtgagcgag cgagcgcgcagctgcctgcaggggcgcctgatgcggtattttctccttacgcatctgtgc ggtatttcacaccgcatacgtcaaagcaaccatagtacgcgccctgtag cggcgcattaagcgcggcgggtgtggtggttacgcgcagcgtgaccgctacacttgccag cgccctagcgcccgctcctttcgctttcttcccttcctttctcgccacgttc gccggctttccccgtcaagctctaaatcgggggctccctttagggttccgatttagtgct ttacggcacctcgaccccaaaaaacttgatttgggtgatggttcacgtagtg ggccatcgccctgatagacggtttttcgccctttgacgttggagtccacgttctttaata gtggactcttgttccaaactggaacaacactcaaccctatctcgggctattcttt tgatttataagggattttgccgatttcggcctattggttaaaaaatgagctgatttaaca aaaatttaacgcgaattttaacaaaatattaacgtttacaattttatggtgcact ctcagtacaatctgctctgatgccgcatagttaagccagccccgacacccgccaacaccc gctgacgcgccctgacgggcttgtctgctcccggcatccgcttacag acaagctgtgaccgtctccgggagctgcatgtgtcagaggttttcaccgtcatcaccgaa acgcgcgagacgaaagggcctcgtgatacgcctatttttataggttaat gtcatgataataatggtttcttagacgtcaggtggcacttttcggggaaatgtgcgcgga acccctatttgtttatttttctaaatacattcaaatatgtatccgctcatgagac aataaccctgataaatgcttcaataatattgaaaaaggaagagtatgagtattcaacatt tccgtgtcgcccttattcccttttttgcggcattttgccttcctgtttttgctcacc cagaaacgctggtgaaagtaaaagatgctgaagatcagttgggtgcacgagtgggttaca tcgaactggatctcaacagcggtaagatccttgagagttttcgcccc gaagaacgttttccaatgatgagcacttttaaagttctgctatgtggcgcggtattatcc cgtattgacgccgggcaagagcaactcggtcgccgcatacactattctcag aatgacttggttgagtactcaccagtcacagaaaagcatcttacggatggcatgacagta agagaattatgcagtgctgccataaccatgagtgataacactgcggc caacttacttctgacaacgatcggaggaccgaaggagctaaccgcttttttgcacaacat gggggatcatgtaactcgccttgatcgttgggaaccggagctgaatga agccataccaaacgacgagcgtgacaccacgatgcctgtagcaatggcaacaacgttgcg caaactattaactggcgaactacttactctagcttcccggcaacaa ttaatagactggatggaggcggataaagttgcaggaccacttctgcgctcggcccttccg gctggctggtttattgctgataaatctggagccggtgagcgtgggtctcg cggtatcattgcagcactggggccagatggtaagccctcccgtatcgtagttatctacac gacggggagtcaggcaactatggatgaacgaaatagacagatcgct gagataggtgcctcactgattaagcattggtaactgtcagaccaagtttactcatatata ctttagattgatttaaaacttcatttttaatttaaaaggatctaggtgaagatcc tttttgataatctcatgaccaaaatcccttaacgtgagttttcgttccactgagcgtcag accccgtagaaaagatcaaaggatcttcttgagatcctttttttctgcgcgtaat ctgctgcttgcaaacaaaaaaaccaccgctaccagcggtggtttgtttgccggatcaaga gctaccaactctttttccgaaggtaactggcttcagcagagcgcagat accaaatactgtccttctagtgtagccgtagttaggccaccacttcaagaactctgtagc accgcctacatacctcgctctgctaatcctgttaccagtggctgctgccagt ggcgataagtcgtgtcttaccgggttggactcaagacgatagttaccggataaggcgcag cggtcgggctgaacggggggttcgtgcacacagcccagcttggag cgaacgacctacaccgaactgagatacctacagcgtgagctatgagaaagcgccacgctt cccgaagggagaaaggcggacaggtatccggtaagcggcagg gtcggaacaggagagcgcacgagggagcttccagggggaaacgcctggtatctttatagt cctgtcgggtttcgccacctctgacttgagcgtcgatttttgtgatgctc gtcaggggggcggagcctatggaaaaacgccagcaacgcggcctttttacggttcctggc cttttgctggccttttgctcacatgt pAAV-U6gRNA(Kcna2-sa sgRNA2)-U6gRNA(Lgi1-sa sgRNA2)-shCaMKII-sadCas9-VP64 used in vitro experiments (SEQ ID NO: 128) (the sequence for shCaMKII is represented by "[XXX]") cctgcaggcagctgcgcgctcgctcgctcactgaggccgcccgggcaaagcccgggcgtc gggcgacctttggtcgcccggcctcagtgagcgagcgagcgcg cagagagggagtggccaactccatcactaggggttcctgcggccgcacgcgtgagggcct atttcccatgattccttcatatttgcatatacgatacaaggctgttaga gagataattggaattaatttgactgtaaacacaaagatattagtacaaaatacgtgacgt agaaagtaataatttcttgggtagtttgcagttttaaaattatgttttaaaatg gactatcatatgcttaccgtaacttgaaagtatttcgatttcttggctttatatatcttg tggaaaggacgaaacaccGCCCCAGCCGGCCCCTTTAATgtttt agtactctggaaacagaatctactaaaacaaggcaaaatgccgtgtttatctcgtcaact tgttggcgagatttttGGGCCCgagggcctatttcccatgattccttcat atttgcatatacgatacaaggctgttagagagataattggaattaatttgactgtaaaca caaagatattagtacaaaatacgtgacgtagaaagtaataatttcttgggt agtttgcagttttaaaattatgttttaaaatggactatcatatgcttaccgtaacttgaa agtatttcgatttcttggctttatatatcttgtggaaaggacgaaacaccgCACT GCTGGGGGAAGAGACCTgttttagtactctggaaacagaatctactaaaacaaggcaaaa tgccgtgtttatctcgtcaacttgttggcgagatttttGCTA GC[XXX]gAATTCGGTACCACCGGTgccaccatggccccaaagaagaagcggaaggtcgg tatccacggagtcccagcagccaagcggaactac atcctgggcctggccatcggcatcaccagcgtgggctacggcatcatcgactacgagaca cgggacgtgatcgatgccggcgtgcggctgttcaaagaggccaac gtggaaaacaacgagggcaggcggagcaagagaggcgccagaaggctgaagcggcggagg cggcatagaatccagagagtgaagaagctgctgttcgact acaacctgctgaccgaccacagcgagctgagcggcatcaacccctacgaggccagagtga agggcctgagccagaagctgagcgaggaagagttctctgccg ccctgctgcacctggccaagagaagaggcgtgcacaacgtgaacgaggtggaagaggaca ccggcaacgagctgtccaccaaagagcagatcagccggaa cagcaaggccctggaagagaaatacgtggccgaactgcagctggaacggctgaagaaaga cggcgaagtgcggggcagcatcaacagattcaagaccagc gactacgtgaaagaagccaaacagctgctgaaggtgcagaaggcctaccaccagctggac cagagcttcatcgacacctacatcgacctgctggaaacccggc ggacctactatgagggacctggcgagggcagccccttcggctggaaggacatcaaagaat ggtacgagatgctgatgggccactgcacctacttccccgaggaa ctgcggagcgtgaagtacgcctacaacgccgacctgtacaacgccctgaacgacctgaac aatctcgtgatcaccagggacgagaacgagaagctggaatatta cgagaagttccagatcatcgagaacgtgttcaagcagaagaagaagcccaccctgaagca gatcgccaaagaaatcctcgtgaacgaagaggatattaagggc tacagagtgaccagcaccggcaagcccgagttcaccaacctgaaggtgtaccacgacatc aaggacattaccgcccggaaagagattattgagaacgccgagc tgctggatcagattgccaagatcctgaccatctaccagagcagcgaggacatccaggaag aactgaccaatctgaactccgagctgacccaggaagagatcgag cagatctctaatctgaagggctataccggcacccacaacctgagcctgaaggccatcaac ctgatcctggacgagctgtggcacaccaacgacaaccagatcgct atcttcaaccggctgaagctggtgcccaagaaggtggacctgtcccagcagaaagagatc cccaccaccctggtggacgacttcatcctgagccccgtcgtgaag agaagcttcatccagagcatcaaagtgatcaacgccatcatcaagaagtacggcctgccc aacgacatcattatcgagctggcccgcgagaagaactccaagga cgcccagaaaatgatcaacgagatgcagaagcggaaccggcagaccaacgagcggatcga ggaaatcatccggaccaccggcaaagagaacgccaagta cctgatcgagaagatcaagctgcacgacatgcaggaaggcaagtgcctgtacagcctgga agccatccctctggaagatctgctgaacaaccccttcaactatga ggtggaccacatcatccccagaagcgtgtccttcgacaacagcttcaacaacaaggtgct cgtgaagcaggaagaagccagcaagaagggcaaccggacccc attccagtacctgagcagcagcgacagcaagatcagctacgaaaccttcaagaagcacat cctgaatctggccaagggcaagggcagaatcagcaagaccaa gaaagagtatctgctggaagaacgggacatcaacaggttctccgtgcagaaagacttcat caaccggaacctggtggataccagatacgccaccagaggcctgat gaacctgctgcggagctacttcagagtgaacaacctggacgtgaaagtgaagtccatcaa tggcggcttcaccagctttctgcggcggaagtggaagtttaagaaa gagcggaacaaggggtacaagcaccacgccgaggacgccctgatcattgccaacgccgat ttcatcttcaaagagtggaagaaactggacaaggccaaaaaa gtgatggaaaaccagatgttcgaggaaaagcaggccgagagcatgcccgagatcgaaacc gagcaggagtacaaagagatcttcatcaccccccaccagatc aagcacattaaggacttcaaggactacaagtacagccaccgggtggacaagaagcctaat agagagctgattaacgacaccctgtactccacccggaaggacg acaagggcaacaccctgatcgtgaacaatctgaacggcctgtacgacaaggacaatgaca agctgaaaaagctgatcaacaagagccccgaaaagctgctgat gtaccaccacgacccccagacctaccagaaactgaagctgattatggaacagtacggcga cgagaagaatcccctgtacaagtactacgaggaaaccgggaa ctacctgaccaagtactccaaaaaggacaacggccccgtgatcaagaagattaagtatta cggcaacaaactgaacgcccatctggacatcaccgacgactacc ccaacagcagaaacaaggtcgtgaagctgtccctgaagccctacagattcgacgtgtacc tggacaatggcgtgtacaagttcgtgaccgtgaagaatctggatgt gatcaaaaaagaaaactactacgaagtgaatagcaagtgctatgaggaagctaagaagct gaagaagatcagcaaccaggccgagtttatcgcctccttctacaa caacgatctgatcaagatcaacggcgagctgtatagagtgatcggcgtgaacaacgacct gctgaaccggatcgaagtgaacatgatcgacatcacctaccgcga gtacctggaaaacatgaacgacaagaggccccccaggatcattaagacaatcgcctccaa gacccagagcattaagaagtacagcacagacattctgggcaac ctgtatgaagtgaaatctaagaagcaccctcagatcatcaaaaagggcaaaaggccggcg gccacgaaaaaggccggccaggcaaaaaagaaaaagggat ccgaggccagcggttccggacgggctgacgcattggacgattttgatctggatatgctgg gaagtgacgccctcgatgattttgaccttgacatgcttggttcggatgcc cttgatgactttgacctcgacatgctcggcagtgacgcccttgatgatttcgacctggac atgctgattaactcaagatgatctagacatatggatatctgactagtctcga gtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataa agcatttttttcactggaccgagcggccgcaggaacccctagtgatggag ttggccactccctctctgcgcgctcgctcgctcactgaggccgggcgaccaaaggtcgcc cgacgcccgggctttgcccgggcggcctcagtgagcgagcgagcg cgcagctgcctgcaggggcgcctgatgcggtattttctccttacgcatctgtgcggtatt tcacaccgcatacgtcaaagcaaccatagtacgcgccctgtagcggcgc attaagcgcggcgggtgtggtggttacgcgcagcgtgaccgctacacttgccagcgccct agcgcccgctcctttcgctttcttcccttcctttctcgccacgttcgccggc tttccccgtcaagctctaaatcgggggctccctttagggttccgatttagtgctttacgg cacctcgaccccaaaaaacttgatttgggtgatggttcacgtagtgggccat cgccctgatagacggtttttcgccctttgacgttggagtccacgttctttaatagtggac tcttgttccaaactggaacaacactcaaccctatctcgggctattcttttgattta taagggattttgccgatttcggcctattggttaaaaaatgagctgatttaacaaaaattt aacgcgaattttaacaaaatattaacgtttacaattttatggtgcactctcagta caatctgctctgatgccgcatagttaagccagccccgacacccgccaacacccgctgacg cgccctgacgggcttgtctgctcccggcatccgcttacagacaagct gtgaccgtctccgggagctgcatgtgtcagaggttttcaccgtcatcaccgaaacgcgcg agacgaaagggcctcgtgatacgcctatttttataggttaatgtcatgat aataatggtttcttagacgtcaggtggcacttttcggggaaatgtgcgcggaacccctat ttgtttatttttctaaatacattcaaatatgtatccgctcatgagacaataacc ctgataaatgcttcaataatattgaaaaaggaagagtatgagtattcaacatttccgtgt cgcccttattcccttttttgcggcattttgccttcctgtttttgctcacccagaaac gctggtgaaagtaaaagatgctgaagatcagttgggtgcacgagtgggttacatcgaact ggatctcaacagcggtaagatccttgagagttttcgccccgaagaac gttttccaatgatgagcacttttaaagttctgctatgtggcgcggtattatcccgtattg acgccgggcaagagcaactcggtcgccgcatacactattctcagaatgactt ggttgagtactcaccagtcacagaaaagcatcttacggatggcatgacagtaagagaatt atgcagtgctgccataaccatgagtgataacactgcggccaacttac ttctgacaacgatcggaggaccgaaggagctaaccgcttttttgcacaacatgggggatc atgtaactcgccttgatcgttgggaaccggagctgaatgaagccata ccaaacgacgagcgtgacaccacgatgcctgtagcaatggcaacaacgttgcgcaaacta ttaactggcgaactacttactctagcttcccggcaacaattaatag actggatggaggcggataaagttgcaggaccacttctgcgctcggcccttccggctggct ggtttattgctgataaatctggagccggtgagcgtgggtctcgcggtatc attgcagcactggggccagatggtaagccctcccgtatcgtagttatctacacgacgggg agtcaggcaactatggatgaacgaaatagacagatcgctgagatag gtgcctcactgattaagcattggtaactgtcagaccaagtttactcatatatactttaga ttgatttaaaacttcatttttaatttaaaaggatctaggtgaagatcctttttgata atctcatgaccaaaatcccttaacgtgagttttcgttccactgagcgtcagaccccgtag aaaagatcaaaggatcttcttgagatcctttttttctgcgcgtaatctgctgct tgcaaacaaaaaaaccaccgctaccagcggtggtttgtttgccggatcaagagctaccaa ctctttttccgaaggtaactggcttcagcagagcgcagataccaaat actgtccttctagtgtagccgtagttaggccaccacttcaagaactctgtagcaccgcct acatacctcgctctgctaatcctgttaccagtggctgctgccagtggcgat aagtcgtgtcttaccgggttggactcaagacgatagttaccggataaggcgcagcggtcg ggctgaacggggggttcgtgcacacagcccagcttggagcgaacg acctacaccgaactgagatacctacagcgtgagctatgagaaagcgccacgcttcccgaa gggagaaaggcggacaggtatccggtaagcggcagggtcgga acaggagagcgcacgagggagcttccagggggaaacgcctggtatctttatagtcctgtc gggtttcgccacctctgacttgagcgtcgatttttgtgatgctcgtcagg ggggcggagcctatggaaaaacgccagcaacgcggcctttttacggttcctggccttttg ctggccttttgctcacatgt pAAV-U6gRNA(Kcnq 2-sa sgRNA6)-U6gRNA(Kcnq 3-sa sgRNA3)-shCaMKII-sadCas9-VP64 used in vitro experiments (SEQ ID NO: 129) cctgcaggcagctgcgcgctcgctcgctcactgaggccgcccgggcaaagcccgggcgtc gggcgacctttggtcgcccggcctcagtgagcgagcgagcgcg cagagagggagtggccaactccatcactaggggttcctgcggccgcacgcgtgagggcct atttcccatgattccttcatatttgcatatacgatacaaggctgttaga gagataattggaattaatttgactgtaaacacaaagatattagtacaaaatacgtgacgt agaaagtaataatttcttgggtagtttgcagttttaaaattatgttttaaaatg gactatcatatgcttaccgtaacttgaaagtatttcgatttcttggctttatatatcttg tggaaaggacgaaacaccTCCTAGCCCGGTAATCCTTGAgtttta gtactctggaaacagaatctactaaaacaaggcaaaatgccgtgtttatctcgtcaactt gttggcgagattttttGGGCCCgagggcctatttcccatgattccttcat atttgcatatacgatacaaggctgttagagagataattggaattaatttgactgtaaaca caaagatattagtacaaaatacgtgacgtagaaagtaataatttcttgggt agtttgcagttttaaaattatgttttaaaatggactatcatatgcttaccgtaacttgaa agtatttcgatttcttggctttatatatcttgtggaaaggacgaaacaccgCTAC TGCCGCTGCAGCGGGGCgttttagtactctggaaacagaatctactaaaacaaggcaaaa tgccgtgtttatctcgtcaacttgttggcgagattttttGCT AGC[XXX]gAATTCGGTACCACCGGTgccaccatggccccaaagaagaagcggaaggtcg gtatccacggagtcccagcagccaagcggaact acatcctgggcctggccatcggcatcaccagcgtgggctacggcatcatcgactacgaga cacgggacgtgatcgatgccggcgtgcggctgttcaaagaggcca acgtggaaaacaacgagggcaggcggagcaagagaggcgccagaaggctgaagcggcgga ggcggcatagaatccagagagtgaagaagctgctgttcg actacaacctgctgaccgaccacagcgagctgagcggcatcaacccctacgaggccagag tgaagggcctgagccagaagctgagcgaggaagagttctctgc cgccctgctgcacctggccaagagaagaggcgtgcacaacgtgaacgaggtggaagagga caccggcaacgagctgtccaccaaagagcagatcagccgg aacagcaaggccctggaagagaaatacgtggccgaactgcagctggaacggctgaagaaa gacggcgaagtgcggggcagcatcaacagattcaagacca gcgactacgtgaaagaagccaaacagctgctgaaggtgcagaaggcctaccaccagctgg accagagcttcatcgacacctacatcgacctgctggaaacccg gcggacctactatgagggacctggcgagggcagccccttcggctggaaggacatcaaaga atggtacgagatgctgatgggccactgcacctacttccccgagg aactgcggagcgtgaagtacgcctacaacgccgacctgtacaacgccctgaacgacctga acaatctcgtgatcaccagggacgagaacgagaagctggaata ttacgagaagttccagatcatcgagaacgtgttcaagcagaagaagaagcccaccctgaa gcagatcgccaaagaaatcctcgtgaacgaagaggatattaagg gctacagagtgaccagcaccggcaagcccgagttcaccaacctgaaggtgtaccacgaca tcaaggacattaccgcccggaaagagattattgagaacgccga gctgctggatcagattgccaagatcctgaccatctaccagagcagcgaggacatccagga agaactgaccaatctgaactccgagctgacccaggaagagatcg agcagatctctaatctgaagggctataccggcacccacaacctgagcctgaaggccatca acctgatcctggacgagctgtggcacaccaacgacaaccagatc gctatcttcaaccggctgaagctggtgcccaagaaggtggacctgtcccagcagaaagag atccccaccaccctggtggacgacttcatcctgagccccgtcgtga agagaagcttcatccagagcatcaaagtgatcaacgccatcatcaagaagtacggcctgc ccaacgacatcattatcgagctggcccgcgagaagaactccaag gacgcccagaaaatgatcaacgagatgcagaagcggaaccggcagaccaacgagcggatc gaggaaatcatccggaccaccggcaaagagaacgccaag tacctgatcgagaagatcaagctgcacgacatgcaggaaggcaagtgcctgtacagcctg gaagccatccctctggaagatctgctgaacaaccccttcaactatg aggtggaccacatcatccccagaagcgtgtccttcgacaacagcttcaacaacaaggtgc tcgtgaagcaggaagaagccagcaagaagggcaaccggaccc cattccagtacctgagcagcagcgacagcaagatcagctacgaaaccttcaagaagcaca tcctgaatctggccaagggcaagggcagaatcagcaagacca agaaagagtatctgctggaagaacgggacatcaacaggttctccgtgcagaaagacttca tcaaccggaacctggtggataccagatacgccaccagaggcctg atgaacctgctgcggagctacttcagagtgaacaacctggacgtgaaagtgaagtccatc aatggcggcttcaccagctttctgcggcggaagtggaagtttaagaa agagcggaacaaggggtacaagcaccacgccgaggacgccctgatcattgccaacgccga tttcatcttcaaagagtggaagaaactggacaaggccaaaaa agtgatggaaaaccagatgttcgaggaaaagcaggccgagagcatgcccgagatcgaaac cgagcaggagtacaaagagatcttcatcaccccccaccagat caagcacattaaggacttcaaggactacaagtacagccaccgggtggacaagaagcctaa tagagagctgattaacgacaccctgtactccacccggaaggac gacaagggcaacaccctgatcgtgaacaatctgaacggcctgtacgacaaggacaatgac aagctgaaaaagctgatcaacaagagccccgaaaagctgctg atgtaccaccacgacccccagacctaccagaaactgaagctgattatggaacagtacggc gacgagaagaatcccctgtacaagtactacgaggaaaccggga actacctgaccaagtactccaaaaaggacaacggccccgtgatcaagaagattaagtatt acggcaacaaactgaacgcccatctggacatcaccgacgactac cccaacagcagaaacaaggtcgtgaagctgtccctgaagccctacagattcgacgtgtac ctggacaatggcgtgtacaagttcgtgaccgtgaagaatctggatgt gatcaaaaaagaaaactactacgaagtgaatagcaagtgctatgaggaagctaagaagct gaagaagatcagcaaccaggccgagtttatcgcctccttctacaa caacgatctgatcaagatcaacggcgagctgtatagagtgatcggcgtgaacaacgacct gctgaaccggatcgaagtgaacatgatcgacatcacctaccgcga gtacctggaaaacatgaacgacaagaggccccccaggatcattaagacaatcgcctccaa gacccagagcattaagaagtacagcacagacattctgggcaac ctgtatgaagtgaaatctaagaagcaccctcagatcatcaaaaagggcaaaaggccggcg gccacgaaaaaggccggccaggcaaaaaagaaaaagggat ccgaggccagcggttccggacgggctgacgcattggacgattttgatctggatatgctgg gaagtgacgccctcgatgattttgaccttgacatgcttggttcggatgcc cttgatgactttgacctcgacatgctcggcagtgacgcccttgatgatttcgacctggac atgctgattaactcaagatgatctagacatatggatatctgactagtctcga gtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataa agcatttttttcactggaccgagcggccgcaggaacccctagtgatggag ttggccactccctctctgcgcgctcgctcgctcactgaggccgggcgaccaaaggtcgcc cgacgcccgggctttgcccgggcggcctcagtgagcgagcgagcg cgcagctgcctgcaggggcgcctgatgcggtattttctccttacgcatctgtgcggtatt tcacaccgcatacgtcaaagcaaccatagtacgcgccctgtagcggcgc attaagcgcggcgggtgtggtggttacgcgcagcgtgaccgctacacttgccagcgccct agcgcccgctcctttcgctttcttcccttcctttctcgccacgttcgccggc tttccccgtcaagctctaaatcgggggctccctttagggttccgatttagtgctttacgg cacctcgaccccaaaaaacttgatttgggtgatggttcacgtagtgggccat cgccctgatagacggtttttcgccctttgacgttggagtccacgttctttaatagtggac tcttgttccaaactggaacaacactcaaccctatctcgggctattcttttgattta taagggattttgccgatttcggcctattggttaaaaaatgagctgatttaacaaaaattt aacgcgaattttaacaaaatattaacgtttacaattttatggtgcactctcagta caatctgctctgatgccgcatagttaagccagccccgacacccgccaacacccgctgacg cgccctgacgggcttgtctgctcccggcatccgcttacagacaagct gtgaccgtctccgggagctgcatgtgtcagaggttttcaccgtcatcaccgaaacgcgcg agacgaaagggcctcgtgatacgcctatttttataggttaatgtcatgat aataatggtttcttagacgtcaggtggcacttttcggggaaatgtgcgcggaacccctat ttgtttatttttctaaatacattcaaatatgtatccgctcatgagacaataacc ctgataaatgcttcaataatattgaaaaaggaagagtatgagtattcaacatttccgtgt cgcccttattcccttttttgcggcattttgccttcctgtttttgctcacccagaaac gctggtgaaagtaaaagatgctgaagatcagttgggtgcacgagtgggttacatcgaact ggatctcaacagcggtaagatccttgagagttttcgccccgaagaac gttttccaatgatgagcacttttaaagttctgctatgtggcgcggtattatcccgtattg acgccgggcaagagcaactcggtcgccgcatacactattctcagaatgactt ggttgagtactcaccagtcacagaaaagcatcttacggatggcatgacagtaagagaatt atgcagtgctgccataaccatgagtgataacactgcggccaacttac ttctgacaacgatcggaggaccgaaggagctaaccgcttttttgcacaacatgggggatc atgtaactcgccttgatcgttgggaaccggagctgaatgaagccata ccaaacgacgagcgtgacaccacgatgcctgtagcaatggcaacaacgttgcgcaaacta ttaactggcgaactacttactctagcttcccggcaacaattaatag actggatggaggcggataaagttgcaggaccacttctgcgctcggcccttccggctggct ggtttattgctgataaatctggagccggtgagcgtgggtctcgcggtatc attgcagcactggggccagatggtaagccctcccgtatcgtagttatctacacgacgggg agtcaggcaactatggatgaacgaaatagacagatcgctgagatag gtgcctcactgattaagcattggtaactgtcagaccaagtttactcatatatactttaga ttgatttaaaacttcatttttaatttaaaaggatctaggtgaagatcctttttgata atctcatgaccaaaatcccttaacgtgagttttcgttccactgagcgtcagaccccgtag aaaagatcaaaggatcttcttgagatcctttttttctgcgcgtaatctgctgct tgcaaacaaaaaaaccaccgctaccagcggtggtttgtttgccggatcaagagctaccaa ctctttttccgaaggtaactggcttcagcagagcgcagataccaaat actgtccttctagtgtagccgtagttaggccaccacttcaagaactctgtagcaccgcct acatacctcgctctgctaatcctgttaccagtggctgctgccagtggcgat aagtcgtgtcttaccgggttggactcaagacgatagttaccggataaggcgcagcggtcg ggctgaacggggggttcgtgcacacagcccagcttggagcgaacg acctacaccgaactgagatacctacagcgtgagctatgagaaagcgccacgcttcccgaa gggagaaaggcggacaggtatccggtaagcggcagggtcgga acaggagagcgcacgagggagcttccagggggaaacgcctggtatctttatagtcctgtc gggtttcgccacctctgacttgagcgtcgatttttgtgatgctcgtcagg ggggcggagcctatggaaaaacgccagcaacgcggcctttttacggttcctggccttttg ctggccttttgctcacatgt

3. Sequences for in vitro screening using patch clamp in DRG neurons- PAIN pAAV-U6gRNA(LacZ-sa sgRNA)-CMV-sadCas9-VP64 used as control in in vitro experiments (SEQ ID NO: 130) cctgcaggcagctgcgcgctcgctcgctcactgaggccgcccgggcaaagcccgggcgtc gggcgacctttggtcgcccggcctcagtgagcgagcgagcgcg cagagagggagtggccaactccatcactaggggttcctgcggccgcacgcgtggtaccga gggcctatttcccatgattccttcatatttgcatatacgatacaaggct gttagagagataattggaattaatttgactgtaaacacaaagatattagtacaaaatacg tgacgtagaaagtaataatttcttgggtagtttgcagttttaaaattatgtttt aaaatggactatcatatgcttaccgtaacttgaaagtatttcgatttcttggctttatat atcttgtggaaaggacgaaacaccGTGCGAATACGCCCACGCG ATgttttagtactctggaaacagaatctactaaaacaaggcaaaatgccgtgtttatctc gtcaacttgttggcgagatttttgcgacgcgtggagttccgcgttacataa cttacggtaaatggcccgcctggctgaccgcccaacgacccccgcccattgacgtcaata atgacgtatgttcccatagtaacgccaatagggactttccattgacgtc aatgggtggagtatttacggtaaactgcccacttggcagtacatcaagtgtatcatatgc caagtacgccccctattgacgtcaatgacggtaaatggcccgcctggca ttatgcccagtacatgaccttatgggactttcctacttggcagtacatctacgtattagt catcgctattaccatggtgatgcggttttggcagtacatcaatgggcgtggata gcggtttgactcacggggatttccaagtctccaccccattgacgtcaatgggagtttgtt ttggcaccaaaatcaacgggactttccaaaatgtcgtaacaactccgccc cattgacgcaaatgggcggtaggcgtgtacggtgggaggtctatataagcagagctcgtt tagtgaaccgtcagatcgcctggagacgccatccacgctgttttgacc tccatagaagacaccgGAATTCGGTACCACCGGTgccaccatggccccaaagaagaagcg gaaggtcggtatccacggagtcccagcagccaag cggaactacatcctgggcctggccatcggcatcaccagcgtgggctacggcatcatcgac tacgagacacgggacgtgatcgatgccggcgtgcggctgttcaaa gaggccaacgtggaaaacaacgagggcaggcggagcaagagaggcgccagaaggctgaag cggcggaggcggcatagaatccagagagtgaagaagct gctgttcgactacaacctgctgaccgaccacagcgagctgagcggcatcaacccctacga ggccagagtgaagggcctgagccagaagctgagcgaggaaga gttctctgccgccctgctgcacctggccaagagaagaggcgtgcacaacgtgaacgaggt ggaagaggacaccggcaacgagctgtccaccaaagagcagat cagccggaacagcaaggccctggaagagaaatacgtggccgaactgcagctggaacggct gaagaaagacggcgaagtgcggggcagcatcaacagattc aagaccagcgactacgtgaaagaagccaaacagctgctgaaggtgcagaaggcctaccac cagctggaccagagcttcatcgacacctacatcgacctgctgg aaacccggcggacctactatgagggacctggcgagggcagccccttcggctggaaggaca tcaaagaatggtacgagatgctgatgggccactgcacctacttc cccgaggaactgcggagcgtgaagtacgcctacaacgccgacctgtacaacgccctgaac gacctgaacaatctcgtgatcaccagggacgagaacgagaag ctggaatattacgagaagttccagatcatcgagaacgtgttcaagcagaagaagaagccc accctgaagcagatcgccaaagaaatcctcgtgaacgaagagg atattaagggctacagagtgaccagcaccggcaagcccgagttcaccaacctgaaggtgt accacgacatcaaggacattaccgcccggaaagagattattgag aacgccgagctgctggatcagattgccaagatcctgaccatctaccagagcagcgaggac atccaggaagaactgaccaatctgaactccgagctgacccagga agagatcgagcagatctctaatctgaagggctataccggcacccacaacctgagcctgaa ggccatcaacctgatcctggacgagctgtggcacaccaacgaca accagatcgctatcttcaaccggctgaagctggtgcccaagaaggtggacctgtcccagc agaaagagatccccaccaccctggtggacgacttcatcctgagccc cgtcgtgaagagaagcttcatccagagcatcaaagtgatcaacgccatcatcaagaagta cggcctgcccaacgacatcattatcgagctggcccgcgagaaga actccaaggacgcccagaaaatgatcaacgagatgcagaagcggaaccggcagaccaacg agcggatcgaggaaatcatccggaccaccggcaaagaga acgccaagtacctgatcgagaagatcaagctgcacgacatgcaggaaggcaagtgcctgt acagcctggaagccatccctctggaagatctgctgaacaacccct tcaactatgaggtggaccacatcatccccagaagcgtgtccttcgacaacagcttcaaca acaaggtgctcgtgaagcaggaagaagccagcaagaagggcaa ccggaccccattccagtacctgagcagcagcgacagcaagatcagctacgaaaccttcaa gaagcacatcctgaatctggccaagggcaagggcagaatcagc aagaccaagaaagagtatctgctggaagaacgggacatcaacaggttctccgtgcagaaa gacttcatcaaccggaacctggtggataccagatacgccaccag aggcctgatgaacctgctgcggagctacttcagagtgaacaacctggacgtgaaagtgaa gtccatcaatggcggcttcaccagctttctgcggcggaagtggaag tttaagaaagagcggaacaaggggtacaagcaccacgccgaggacgccctgatcattgcc aacgccgatttcatcttcaaagagtggaagaaactggacaagg ccaaaaaagtgatggaaaaccagatgttcgaggaaaagcaggccgagagcatgcccgaga tcgaaaccgagcaggagtacaaagagatcttcatcacccccc accagatcaagcacattaaggacttcaaggactacaagtacagccaccgggtggacaaga agcctaatagagagctgattaacgacaccctgtactccacccgg aaggacgacaagggcaacaccctgatcgtgaacaatctgaacggcctgtacgacaaggac aatgacaagctgaaaaagctgatcaacaagagccccgaaaa gctgctgatgtaccaccacgacccccagacctaccagaaactgaagctgattatggaaca gtacggcgacgagaagaatcccctgtacaagtactacgaggaaa ccgggaactacctgaccaagtactccaaaaaggacaacggccccgtgatcaagaagatta agtattacggcaacaaactgaacgcccatctggacatcaccgac gactaccccaacagcagaaacaaggtcgtgaagctgtccctgaagccctacagattcgac gtgtacctggacaatggcgtgtacaagttcgtgaccgtgaagaatc tggatgtgatcaaaaaagaaaactactacgaagtgaatagcaagtgctatgaggaagcta agaagctgaagaagatcagcaaccaggccgagtttatcgcctcct tctacaacaacgatctgatcaagatcaacggcgagctgtatagagtgatcggcgtgaaca acgacctgctgaaccggatcgaagtgaacatgatcgacatcaccta ccgcgagtacctggaaaacatgaacgacaagaggccccccaggatcattaagacaatcgc ctccaagacccagagcattaagaagtacagcacagacattctg ggcaacctgtatgaagtgaaatctaagaagcaccctcagatcatcaaaaagggcaaaagg ccggcggccacgaaaaaggccggccaggcaaaaaagaaaa agggatccgaggccagcggttccggacgggctgacgcattggacgattttgatctggata tgctgggaagtgacgccctcgatgattttgaccttgacatgcttggttcg gatgcccttgatgactttgacctcgacatgctcggcagtgacgcccttgatgatttcgac ctggacatgctgattaactcaagatgatctagacatatggatatctgactag tctcgagtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcac aaataaagcatttttttcactggaccgagcggccgcaggaacccctagtg atggagttggccactccctctctgcgcgctcgctcgctcactgaggccgggcgaccaaag gtcgcccgacgcccgggctttgcccgggcggcctcagtgagcgag cgagcgcgcagctgcctgcaggggcgcctgatgcggtattttctccttacgcatctgtgc ggtatttcacaccgcatacgtcaaagcaaccatagtacgcgccctgtag cggcgcattaagcgcggcgggtgtggtggttacgcgcagcgtgaccgctacacttgccag cgccctagcgcccgctcctttcgctttcttcccttcctttctcgccacgttc gccggctttccccgtcaagctctaaatcgggggctccctttagggttccgatttagtgct ttacggcacctcgaccccaaaaaacttgatttgggtgatggttcacgtagtg ggccatcgccctgatagacggtttttcgccctttgacgttggagtccacgttctttaata gtggactcttgttccaaactggaacaacactcaaccctatctcgggctattcttt tgatttataagggattttgccgatttcggcctattggttaaaaaatgagctgatttaaca aaaatttaacgcgaattttaacaaaatattaacgtttacaattttatggtgcact ctcagtacaatctgctctgatgccgcatagttaagccagccccgacacccgccaacaccc gctgacgcgccctgacgggcttgtctgctcccggcatccgcttacag acaagctgtgaccgtctccgggagctgcatgtgtcagaggttttcaccgtcatcaccgaa acgcgcgagacgaaagggcctcgtgatacgcctatttttataggttaat gtcatgataataatggtttcttagacgtcaggtggcacttttcggggaaatgtgcgcgga acccctatttgtttatttttctaaatacattcaaatatgtatccgctcatgagac aataaccctgataaatgcttcaataatattgaaaaaggaagagtatgagtattcaacatt tccgtgtcgcccttattcccttttttgcggcattttgccttcctgtttttgctcacc cagaaacgctggtgaaagtaaaagatgctgaagatcagttgggtgcacgagtgggttaca tcgaactggatctcaacagcggtaagatccttgagagttttcgcccc gaagaacgttttccaatgatgagcacttttaaagttctgctatgtggcgcggtattatcc cgtattgacgccgggcaagagcaactcggtcgccgcatacactattctcag aatgacttggttgagtactcaccagtcacagaaaagcatcttacggatggcatgacagta agagaattatgcagtgctgccataaccatgagtgataacactgcggc caacttacttctgacaacgatcggaggaccgaaggagctaaccgcttttttgcacaacat gggggatcatgtaactcgccttgatcgttgggaaccggagctgaatga agccataccaaacgacgagcgtgacaccacgatgcctgtagcaatggcaacaacgttgcg caaactattaactggcgaactacttactctagcttcccggcaacaa ttaatagactggatggaggcggataaagttgcaggaccacttctgcgctcggcccttccg gctggctggtttattgctgataaatctggagccggtgagcgtgggtctcg cggtatcattgcagcactggggccagatggtaagccctcccgtatcgtagttatctacac gacggggagtcaggcaactatggatgaacgaaatagacagatcgct gagataggtgcctcactgattaagcattggtaactgtcagaccaagtttactcatatata ctttagattgatttaaaacttcatttttaatttaaaaggatctaggtgaagatcc tttttgataatctcatgaccaaaatcccttaacgtgagttttcgttccactgagcgtcag accccgtagaaaagatcaaaggatcttcttgagatcctttttttctgcgcgtaat ctgctgcttgcaaacaaaaaaaccaccgctaccagcggtggtttgtttgccggatcaaga gctaccaactctttttccgaaggtaactggcttcagcagagcgcagat accaaatactgtccttctagtgtagccgtagttaggccaccacttcaagaactctgtagc accgcctacatacctcgctctgctaatcctgttaccagtggctgctgccagt ggcgataagtcgtgtcttaccgggttggactcaagacgatagttaccggataaggcgcag cggtcgggctgaacggggggttcgtgcacacagcccagcttggag cgaacgacctacaccgaactgagatacctacagcgtgagctatgagaaagcgccacgctt cccgaagggagaaaggcggacaggtatccggtaagcggcagg gtcggaacaggagagcgcacgagggagcttccagggggaaacgcctggtatctttatagt cctgtcgggtttcgccacctctgacttgagcgtcgatttttgtgatgctc gtcaggggggcggagcctatggaaaaacgccagcaacgcggcctttttacggttcctggc cttttgctggccttttgctcacatgt pAAV-U6gRNA(Kcna2-sa sgRNA2)-CMV-sadCas9-VP64 used in in vitro experiments (SEQ ID NO: 131) cctgcaggcagctgcgcgctcgctcgctcactgaggccgcccgggcaaagcccgggcgtc gggcgacctttggtcgcccggcctcagtgagcgagcgagcgcg cagagagggagtggccaactccatcactaggggttcctgcggccgcacgcgtggtaccga gggcctatttcccatgattccttcatatttgcatatacgatacaaggct gttagagagataattggaattaatttgactgtaaacacaaagatattagtacaaaatacg tgacgtagaaagtaataatttcttgggtagtttgcagttttaaaattatgtttt aaaatggactatcatatgcttaccgtaacttgaaagtatttcgatttcttggctttatat atcttgtggaaaggacgaaacaccGCCCCAGCCGGCCCCTTTA ATgttttagtactctggaaacagaatctactaaaacaaggcaaaatgccgtgtttatctc gtcaacttgttggcgagatttttgcgacgcgtggagttccgcgttacataa cttacggtaaatggcccgcctggctgaccgcccaacgacccccgcccattgacgtcaata atgacgtatgttcccatagtaacgccaatagggactttccattgacgtc aatgggtggagtatttacggtaaactgcccacttggcagtacatcaagtgtatcatatgc caagtacgccccctattgacgtcaatgacggtaaatggcccgcctggca ttatgcccagtacatgaccttatgggactttcctacttggcagtacatctacgtattagt catcgctattaccatggtgatgcggttttggcagtacatcaatgggcgtggata gcggtttgactcacggggatttccaagtctccaccccattgacgtcaatgggagtttgtt ttggcaccaaaatcaacgggactttccaaaatgtcgtaacaactccgccc cattgacgcaaatgggcggtaggcgtgtacggtgggaggtctatataagcagagctcgtt tagtgaaccgtcagatcgcctggagacgccatccacgctgttttgacc tccatagaagacaccgGAATTCGGTACCACCGGTgccaccatggccccaaagaagaagcg gaaggtcggtatccacggagtcccagcagccaag cggaactacatcctgggcctggccatcggcatcaccagcgtgggctacggcatcatcgac tacgagacacgggacgtgatcgatgccggcgtgcggctgttcaaa gaggccaacgtggaaaacaacgagggcaggcggagcaagagaggcgccagaaggctgaag cggcggaggcggcatagaatccagagagtgaagaagct gctgttcgactacaacctgctgaccgaccacagcgagctgagcggcatcaacccctacga ggccagagtgaagggcctgagccagaagctgagcgaggaaga gttctctgccgccctgctgcacctggccaagagaagaggcgtgcacaacgtgaacgaggt ggaagaggacaccggcaacgagctgtccaccaaagagcagat cagccggaacagcaaggccctggaagagaaatacgtggccgaactgcagctggaacggct gaagaaagacggcgaagtgcggggcagcatcaacagattc aagaccagcgactacgtgaaagaagccaaacagctgctgaaggtgcagaaggcctaccac cagctggaccagagcttcatcgacacctacatcgacctgctgg aaacccggcggacctactatgagggacctggcgagggcagccccttcggctggaaggaca tcaaagaatggtacgagatgctgatgggccactgcacctacttc cccgaggaactgcggagcgtgaagtacgcctacaacgccgacctgtacaacgccctgaac gacctgaacaatctcgtgatcaccagggacgagaacgagaag ctggaatattacgagaagttccagatcatcgagaacgtgttcaagcagaagaagaagccc accctgaagcagatcgccaaagaaatcctcgtgaacgaagagg atattaagggctacagagtgaccagcaccggcaagcccgagttcaccaacctgaaggtgt accacgacatcaaggacattaccgcccggaaagagattattgag aacgccgagctgctggatcagattgccaagatcctgaccatctaccagagcagcgaggac atccaggaagaactgaccaatctgaactccgagctgacccagga agagatcgagcagatctctaatctgaagggctataccggcacccacaacctgagcctgaa ggccatcaacctgatcctggacgagctgtggcacaccaacgaca accagatcgctatcttcaaccggctgaagctggtgcccaagaaggtggacctgtcccagc agaaagagatccccaccaccctggtggacgacttcatcctgagccc cgtcgtgaagagaagcttcatccagagcatcaaagtgatcaacgccatcatcaagaagta cggcctgcccaacgacatcattatcgagctggcccgcgagaaga actccaaggacgcccagaaaatgatcaacgagatgcagaagcggaaccggcagaccaacg agcggatcgaggaaatcatccggaccaccggcaaagaga acgccaagtacctgatcgagaagatcaagctgcacgacatgcaggaaggcaagtgcctgt acagcctggaagccatccctctggaagatctgctgaacaacccct tcaactatgaggtggaccacatcatccccagaagcgtgtccttcgacaacagcttcaaca acaaggtgctcgtgaagcaggaagaagccagcaagaagggcaa ccggaccccattccagtacctgagcagcagcgacagcaagatcagctacgaaaccttcaa gaagcacatcctgaatctggccaagggcaagggcagaatcagc aagaccaagaaagagtatctgctggaagaacgggacatcaacaggttctccgtgcagaaa gacttcatcaaccggaacctggtggataccagatacgccaccag aggcctgatgaacctgctgcggagctacttcagagtgaacaacctggacgtgaaagtgaa gtccatcaatggcggcttcaccagctttctgcggcggaagtggaag tttaagaaagagcggaacaaggggtacaagcaccacgccgaggacgccctgatcattgcc aacgccgatttcatcttcaaagagtggaagaaactggacaagg ccaaaaaagtgatggaaaaccagatgttcgaggaaaagcaggccgagagcatgcccgaga tcgaaaccgagcaggagtacaaagagatcttcatcacccccc accagatcaagcacattaaggacttcaaggactacaagtacagccaccgggtggacaaga agcctaatagagagctgattaacgacaccctgtactccacccgg aaggacgacaagggcaacaccctgatcgtgaacaatctgaacggcctgtacgacaaggac aatgacaagctgaaaaagctgatcaacaagagccccgaaaa gctgctgatgtaccaccacgacccccagacctaccagaaactgaagctgattatggaaca gtacggcgacgagaagaatcccctgtacaagtactacgaggaaa ccgggaactacctgaccaagtactccaaaaaggacaacggccccgtgatcaagaagatta agtattacggcaacaaactgaacgcccatctggacatcaccgac gactaccccaacagcagaaacaaggtcgtgaagctgtccctgaagccctacagattcgac gtgtacctggacaatggcgtgtacaagttcgtgaccgtgaagaatc tggatgtgatcaaaaaagaaaactactacgaagtgaatagcaagtgctatgaggaagcta agaagctgaagaagatcagcaaccaggccgagtttatcgcctcct tctacaacaacgatctgatcaagatcaacggcgagctgtatagagtgatcggcgtgaaca acgacctgctgaaccggatcgaagtgaacatgatcgacatcaccta ccgcgagtacctggaaaacatgaacgacaagaggccccccaggatcattaagacaatcgc ctccaagacccagagcattaagaagtacagcacagacattctg ggcaacctgtatgaagtgaaatctaagaagcaccctcagatcatcaaaaagggcaaaagg ccggcggccacgaaaaaggccggccaggcaaaaaagaaaa agggatccgaggccagcggttccggacgggctgacgcattggacgattttgatctggata tgctgggaagtgacgccctcgatgattttgaccttgacatgcttggttcg gatgcccttgatgactttgacctcgacatgctcggcagtgacgcccttgatgatttcgac ctggacatgctgattaactcaagatgatctagacatatggatatctgactag tctcgagtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcac aaataaagcatttttttcactggaccgagcggccgcaggaacccctagtg atggagttggccactccctctctgcgcgctcgctcgctcactgaggccgggcgaccaaag gtcgcccgacgcccgggctttgcccgggcggcctcagtgagcgag cgagcgcgcagctgcctgcaggggcgcctgatgcggtattttctccttacgcatctgtgc ggtatttcacaccgcatacgtcaaagcaaccatagtacgcgccctgtag cggcgcattaagcgcggcgggtgtggtggttacgcgcagcgtgaccgctacacttgccag cgccctagcgcccgctcctttcgctttcttcccttcctttctcgccacgttc gccggctttccccgtcaagctctaaatcgggggctccctttagggttccgatttagtgct ttacggcacctcgaccccaaaaaacttgatttgggtgatggttcacgtagtg ggccatcgccctgatagacggtttttcgccctttgacgttggagtccacgttctttaata gtggactcttgttccaaactggaacaacactcaaccctatctcgggctattcttt tgatttataagggattttgccgatttcggcctattggttaaaaaatgagctgatttaaca aaaatttaacgcgaattttaacaaaatattaacgtttacaattttatggtgcact ctcagtacaatctgctctgatgccgcatagttaagccagccccgacacccgccaacaccc gctgacgcgccctgacgggcttgtctgctcccggcatccgcttacag acaagctgtgaccgtctccgggagctgcatgtgtcagaggttttcaccgtcatcaccgaa acgcgcgagacgaaagggcctcgtgatacgcctatttttataggttaat gtcatgataataatggtttcttagacgtcaggtggcacttttcggggaaatgtgcgcgga acccctatttgtttatttttctaaatacattcaaatatgtatccgctcatgagac aataaccctgataaatgcttcaataatattgaaaaaggaagagtatgagtattcaacatt tccgtgtcgcccttattcccttttttgcggcattttgccttcctgtttttgctcacc cagaaacgctggtgaaagtaaaagatgctgaagatcagttgggtgcacgagtgggttaca tcgaactggatctcaacagcggtaagatccttgagagttttcgcccc gaagaacgttttccaatgatgagcacttttaaagttctgctatgtggcgcggtattatcc cgtattgacgccgggcaagagcaactcggtcgccgcatacactattctcag aatgacttggttgagtactcaccagtcacagaaaagcatcttacggatggcatgacagta agagaattatgcagtgctgccataaccatgagtgataacactgcggc caacttacttctgacaacgatcggaggaccgaaggagctaaccgcttttttgcacaacat gggggatcatgtaactcgccttgatcgttgggaaccggagctgaatga agccataccaaacgacgagcgtgacaccacgatgcctgtagcaatggcaacaacgttgcg caaactattaactggcgaactacttactctagcttcccggcaacaa ttaatagactggatggaggcggataaagttgcaggaccacttctgcgctcggcccttccg gctggctggtttattgctgataaatctggagccggtgagcgtgggtctcg cggtatcattgcagcactggggccagatggtaagccctcccgtatcgtagttatctacac gacggggagtcaggcaactatggatgaacgaaatagacagatcgct gagataggtgcctcactgattaagcattggtaactgtcagaccaagtttactcatatata ctttagattgatttaaaacttcatttttaatttaaaaggatctaggtgaagatcc tttttgataatctcatgaccaaaatcccttaacgtgagttttcgttccactgagcgtcag accccgtagaaaagatcaaaggatcttcttgagatcctttttttctgcgcgtaat ctgctgcttgcaaacaaaaaaaccaccgctaccagcggtggtttgtttgccggatcaaga gctaccaactctttttccgaaggtaactggcttcagcagagcgcagat accaaatactgtccttctagtgtagccgtagttaggccaccacttcaagaactctgtagc accgcctacatacctcgctctgctaatcctgttaccagtggctgctgccagt ggcgataagtcgtgtcttaccgggttggactcaagacgatagttaccggataaggcgcag cggtcgggctgaacggggggttcgtgcacacagcccagcttggag cgaacgacctacaccgaactgagatacctacagcgtgagctatgagaaagcgccacgctt cccgaagggagaaaggcggacaggtatccggtaagcggcagg gtcggaacaggagagcgcacgagggagcttccagggggaaacgcctggtatctttatagt cctgtcgggtttcgccacctctgacttgagcgtcgatttttgtgatgctc gtcaggggggcggagcctatggaaaaacgccagcaacgcggcctttttacggttcctggc cttttgctggccttttgctcacatgt pAAV-U6gRNA(Kcnj2-sa sgRNA1)-CMV-sadCas9-VP64 used in in vitro experiments (SEQ ID NO: 132) cctgcaggcagctgcgcgctcgctcgctcactgaggccgcccgggcaaagcccgggcgtc gggcgacctttggtcgcccggcctcagtgagcgagcgagcgcg cagagagggagtggccaactccatcactaggggttcctgcggccgcacgcgtggtaccga gggcctatttcccatgattccttcatatttgcatatacgatacaaggct gttagagagataattggaattaatttgactgtaaacacaaagatattagtacaaaatacg tgacgtagaaagtaataatttcttgggtagtttgcagttttaaaattatgtttt aaaatggactatcatatgcttaccgtaacttgaaagtatttcgatttcttggctttatat atcttgtggaaaggacgaaacaccTCCTCCTCCTGATGGCGGT TCGttttagtactctggaaacagaatctactaaaacaaggcaaaatgccgtgtttatctc gtcaacttgttggcgagatttttgcgacgcgtggagttccgcgttacataa cttacggtaaatggcccgcctggctgaccgcccaacgacccccgcccattgacgtcaata atgacgtatgttcccatagtaacgccaatagggactttccattgacgtc aatgggtggagtatttacggtaaactgcccacttggcagtacatcaagtgtatcatatgc caagtacgccccctattgacgtcaatgacggtaaatggcccgcctggca ttatgcccagtacatgaccttatgggactttcctacttggcagtacatctacgtattagt catcgctattaccatggtgatgcggttttggcagtacatcaatgggcgtggata gcggtttgactcacggggatttccaagtctccaccccattgacgtcaatgggagtttgtt ttggcaccaaaatcaacgggactttccaaaatgtcgtaacaactccgccc cattgacgcaaatgggcggtaggcgtgtacggtgggaggtctatataagcagagctcgtt tagtgaaccgtcagatcgcctggagacgccatccacgctgttttgacc tccatagaagacaccgGAATTCGGTACCACCGGTgccaccatggccccaaagaagaagcg gaaggtcggtatccacggagtcccagcagccaag cggaactacatcctgggcctggccatcggcatcaccagcgtgggctacggcatcatcgac tacgagacacgggacgtgatcgatgccggcgtgcggctgttcaaa gaggccaacgtggaaaacaacgagggcaggcggagcaagagaggcgccagaaggctgaag cggcggaggcggcatagaatccagagagtgaagaagct gctgttcgactacaacctgctgaccgaccacagcgagctgagcggcatcaacccctacga ggccagagtgaagggcctgagccagaagctgagcgaggaaga gttctctgccgccctgctgcacctggccaagagaagaggcgtgcacaacgtgaacgaggt ggaagaggacaccggcaacgagctgtccaccaaagagcagat cagccggaacagcaaggccctggaagagaaatacgtggccgaactgcagctggaacggct gaagaaagacggcgaagtgcggggcagcatcaacagattc aagaccagcgactacgtgaaagaagccaaacagctgctgaaggtgcagaaggcctaccac cagctggaccagagcttcatcgacacctacatcgacctgctgg aaacccggcggacctactatgagggacctggcgagggcagccccttcggctggaaggaca tcaaagaatggtacgagatgctgatgggccactgcacctacttc cccgaggaactgcggagcgtgaagtacgcctacaacgccgacctgtacaacgccctgaac gacctgaacaatctcgtgatcaccagggacgagaacgagaag ctggaatattacgagaagttccagatcatcgagaacgtgttcaagcagaagaagaagccc accctgaagcagatcgccaaagaaatcctcgtgaacgaagagg atattaagggctacagagtgaccagcaccggcaagcccgagttcaccaacctgaaggtgt accacgacatcaaggacattaccgcccggaaagagattattgag aacgccgagctgctggatcagattgccaagatcctgaccatctaccagagcagcgaggac atccaggaagaactgaccaatctgaactccgagctgacccagga agagatcgagcagatctctaatctgaagggctataccggcacccacaacctgagcctgaa ggccatcaacctgatcctggacgagctgtggcacaccaacgaca accagatcgctatcttcaaccggctgaagctggtgcccaagaaggtggacctgtcccagc agaaagagatccccaccaccctggtggacgacttcatcctgagccc cgtcgtgaagagaagcttcatccagagcatcaaagtgatcaacgccatcatcaagaagta cggcctgcccaacgacatcattatcgagctggcccgcgagaaga actccaaggacgcccagaaaatgatcaacgagatgcagaagcggaaccggcagaccaacg agcggatcgaggaaatcatccggaccaccggcaaagaga acgccaagtacctgatcgagaagatcaagctgcacgacatgcaggaaggcaagtgcctgt acagcctggaagccatccctctggaagatctgctgaacaacccct tcaactatgaggtggaccacatcatccccagaagcgtgtccttcgacaacagcttcaaca acaaggtgctcgtgaagcaggaagaagccagcaagaagggcaa ccggaccccattccagtacctgagcagcagcgacagcaagatcagctacgaaaccttcaa gaagcacatcctgaatctggccaagggcaagggcagaatcagc aagaccaagaaagagtatctgctggaagaacgggacatcaacaggttctccgtgcagaaa gacttcatcaaccggaacctggtggataccagatacgccaccag aggcctgatgaacctgctgcggagctacttcagagtgaacaacctggacgtgaaagtgaa gtccatcaatggcggcttcaccagctttctgcggcggaagtggaag tttaagaaagagcggaacaaggggtacaagcaccacgccgaggacgccctgatcattgcc aacgccgatttcatcttcaaagagtggaagaaactggacaagg ccaaaaaagtgatggaaaaccagatgttcgaggaaaagcaggccgagagcatgcccgaga tcgaaaccgagcaggagtacaaagagatcttcatcacccccc accagatcaagcacattaaggacttcaaggactacaagtacagccaccgggtggacaaga agcctaatagagagctgattaacgacaccctgtactccacccgg aaggacgacaagggcaacaccctgatcgtgaacaatctgaacggcctgtacgacaaggac aatgacaagctgaaaaagctgatcaacaagagccccgaaaa gctgctgatgtaccaccacgacccccagacctaccagaaactgaagctgattatggaaca gtacggcgacgagaagaatcccctgtacaagtactacgaggaaa ccgggaactacctgaccaagtactccaaaaaggacaacggccccgtgatcaagaagatta agtattacggcaacaaactgaacgcccatctggacatcaccgac gactaccccaacagcagaaacaaggtcgtgaagctgtccctgaagccctacagattcgac gtgtacctggacaatggcgtgtacaagttcgtgaccgtgaagaatc tggatgtgatcaaaaaagaaaactactacgaagtgaatagcaagtgctatgaggaagcta agaagctgaagaagatcagcaaccaggccgagtttatcgcctcct tctacaacaacgatctgatcaagatcaacggcgagctgtatagagtgatcggcgtgaaca acgacctgctgaaccggatcgaagtgaacatgatcgacatcaccta ccgcgagtacctggaaaacatgaacgacaagaggccccccaggatcattaagacaatcgc ctccaagacccagagcattaagaagtacagcacagacattctg ggcaacctgtatgaagtgaaatctaagaagcaccctcagatcatcaaaaagggcaaaagg ccggcggccacgaaaaaggccggccaggcaaaaaagaaaa agggatccgaggccagcggttccggacgggctgacgcattggacgattttgatctggata tgctgggaagtgacgccctcgatgattttgaccttgacatgcttggttcg gatgcccttgatgactttgacctcgacatgctcggcagtgacgcccttgatgatttcgac ctggacatgctgattaactcaagatgatctagacatatggatatctgactag tctcgagtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcac aaataaagcatttttttcactggaccgagcggccgcaggaacccctagtg atggagttggccactccctctctgcgcgctcgctcgctcactgaggccgggcgaccaaag gtcgcccgacgcccgggctttgcccgggcggcctcagtgagcgag cgagcgcgcagctgcctgcaggggcgcctgatgcggtattttctccttacgcatctgtgc ggtatttcacaccgcatacgtcaaagcaaccatagtacgcgccctgtag cggcgcattaagcgcggcgggtgtggtggttacgcgcagcgtgaccgctacacttgccag cgccctagcgcccgctcctttcgctttcttcccttcctttctcgccacgttc gccggctttccccgtcaagctctaaatcgggggctccctttagggttccgatttagtgct ttacggcacctcgaccccaaaaaacttgatttgggtgatggttcacgtagtg ggccatcgccctgatagacggtttttcgccctttgacgttggagtccacgttctttaata gtggactcttgttccaaactggaacaacactcaaccctatctcgggctattcttt tgatttataagggattttgccgatttcggcctattggttaaaaaatgagctgatttaaca aaaatttaacgcgaattttaacaaaatattaacgtttacaattttatggtgcact ctcagtacaatctgctctgatgccgcatagttaagccagccccgacacccgccaacaccc gctgacgcgccctgacgggcttgtctgctcccggcatccgcttacag acaagctgtgaccgtctccgggagctgcatgtgtcagaggttttcaccgtcatcaccgaa acgcgcgagacgaaagggcctcgtgatacgcctatttttataggttaat gtcatgataataatggtttcttagacgtcaggtggcacttttcggggaaatgtgcgcgga acccctatttgtttatttttctaaatacattcaaatatgtatccgctcatgagac aataaccctgataaatgcttcaataatattgaaaaaggaagagtatgagtattcaacatt tccgtgtcgcccttattcccttttttgcggcattttgccttcctgtttttgctcacc cagaaacgctggtgaaagtaaaagatgctgaagatcagttgggtgcacgagtgggttaca tcgaactggatctcaacagcggtaagatccttgagagttttcgcccc gaagaacgttttccaatgatgagcacttttaaagttctgctatgtggcgcggtattatcc cgtattgacgccgggcaagagcaactcggtcgccgcatacactattctcag aatgacttggttgagtactcaccagtcacagaaaagcatcttacggatggcatgacagta agagaattatgcagtgctgccataaccatgagtgataacactgcggc caacttacttctgacaacgatcggaggaccgaaggagctaaccgcttttttgcacaacat gggggatcatgtaactcgccttgatcgttgggaaccggagctgaatga agccataccaaacgacgagcgtgacaccacgatgcctgtagcaatggcaacaacgttgcg caaactattaactggcgaactacttactctagcttcccggcaacaa ttaatagactggatggaggcggataaagttgcaggaccacttctgcgctcggcccttccg gctggctggtttattgctgataaatctggagccggtgagcgtgggtctcg cggtatcattgcagcactggggccagatggtaagccctcccgtatcgtagttatctacac gacggggagtcaggcaactatggatgaacgaaatagacagatcgct gagataggtgcctcactgattaagcattggtaactgtcagaccaagtttactcatatata ctttagattgatttaaaacttcatttttaatttaaaaggatctaggtgaagatcc tttttgataatctcatgaccaaaatcccttaacgtgagttttcgttccactgagcgtcag accccgtagaaaagatcaaaggatcttcttgagatcctttttttctgcgcgtaat ctgctgcttgcaaacaaaaaaaccaccgctaccagcggtggtttgtttgccggatcaaga gctaccaactctttttccgaaggtaactggcttcagcagagcgcagat accaaatactgtccttctagtgtagccgtagttaggccaccacttcaagaactctgtagc accgcctacatacctcgctctgctaatcctgttaccagtggctgctgccagt ggcgataagtcgtgtcttaccgggttggactcaagacgatagttaccggataaggcgcag cggtcgggctgaacggggggttcgtgcacacagcccagcttggag cgaacgacctacaccgaactgagatacctacagcgtgagctatgagaaagcgccacgctt cccgaagggagaaaggcggacaggtatccggtaagcggcagg gtcggaacaggagagcgcacgagggagcttccagggggaaacgcctggtatctttatagt cctgtcgggtttcgccacctctgacttgagcgtcgatttttgtgatgctc gtcaggggggcggagcctatggaaaaacgccagcaacgcggcctttttacggttcctggc cttttgctggccttttgctcacatgt pAAV-U6gRNA(Kcnj2-sa sgRNA2)-CMV-sadCas9-VP64 used in in vitro experiments (SEQ ID NO: 133) cctgcaggcagctgcgcgctcgctcgctcactgaggccgcccgggcaaagcccgggcgtc gggcgacctttggtcgcccggcctcagtgagcgagcgagcgcg cagagagggagtggccaactccatcactaggggttcctgcggccgcacgcgtggtaccga gggcctatttcccatgattccttcatatttgcatatacgatacaaggct gttagagagataattggaattaatttgactgtaaacacaaagatattagtacaaaatacg tgacgtagaaagtaataatttcttgggtagtttgcagttttaaaattatgtttt aaaatggactatcatatgcttaccgtaacttgaaagtatttcgatttcttggctttatat atcttgtggaaaggacgaaacaccGCCCCGGGAACCGCCATCA GGGttttagtactctggaaacagaatctactaaaacaaggcaaaatgccgtgtttatctc gtcaacttgttggcgagatttttgcgacgcgtggagttccgcgttacata acttacggtaaatggcccgcctggctgaccgcccaacgacccccgcccattgacgtcaat aatgacgtatgttcccatagtaacgccaatagggactttccattgacg tcaatgggtggagtatttacggtaaactgcccacttggcagtacatcaagtgtatcatat gccaagtacgccccctattgacgtcaatgacggtaaatggcccgcctgg cattatgcccagtacatgaccttatgggactttcctacttggcagtacatctacgtatta gtcatcgctattaccatggtgatgcggttttggcagtacatcaatgggcgtgg atagcggtttgactcacggggatttccaagtctccaccccattgacgtcaatgggagttt gttttggcaccaaaatcaacgggactttccaaaatgtcgtaacaactccg ccccattgacgcaaatgggcggtaggcgtgtacggtgggaggtctatataagcagagctc gtttagtgaaccgtcagatcgcctggagacgccatccacgctgttttg acctccatagaagacaccgGAATTCGGTACCACCGGTgccaccatggccccaaagaagaa gcggaaggtcggtatccacggagtcccagcagcc aagcggaactacatcctgggcctggccatcggcatcaccagcgtgggctacggcatcatc gactacgagacacgggacgtgatcgatgccggcgtgcggctgttc aaagaggccaacgtggaaaacaacgagggcaggcggagcaagagaggcgccagaaggctg aagcggcggaggcggcatagaatccagagagtgaaga agctgctgttcgactacaacctgctgaccgaccacagcgagctgagcggcatcaacccct acgaggccagagtgaagggcctgagccagaagctgagcgagga agagttctctgccgccctgctgcacctggccaagagaagaggcgtgcacaacgtgaacga ggtggaagaggacaccggcaacgagctgtccaccaaagagca gatcagccggaacagcaaggccctggaagagaaatacgtggccgaactgcagctggaacg gctgaagaaagacggcgaagtgcggggcagcatcaacaga ttcaagaccagcgactacgtgaaagaagccaaacagctgctgaaggtgcagaaggcctac caccagctggaccagagcttcatcgacacctacatcgacctgct ggaaacccggcggacctactatgagggacctggcgagggcagccccttcggctggaagga catcaaagaatggtacgagatgctgatgggccactgcacctact tccccgaggaactgcggagcgtgaagtacgcctacaacgccgacctgtacaacgccctga acgacctgaacaatctcgtgatcaccagggacgagaacgagaa gctggaatattacgagaagttccagatcatcgagaacgtgttcaagcagaagaagaagcc caccctgaagcagatcgccaaagaaatcctcgtgaacgaagag gatattaagggctacagagtgaccagcaccggcaagcccgagttcaccaacctgaaggtg taccacgacatcaaggacattaccgcccggaaagagattattga gaacgccgagctgctggatcagattgccaagatcctgaccatctaccagagcagcgagga catccaggaagaactgaccaatctgaactccgagctgacccagg aagagatcgagcagatctctaatctgaagggctataccggcacccacaacctgagcctga aggccatcaacctgatcctggacgagctgtggcacaccaacgac aaccagatcgctatcttcaaccggctgaagctggtgcccaagaaggtggacctgtcccag cagaaagagatccccaccaccctggtggacgacttcatcctgagc cccgtcgtgaagagaagcttcatccagagcatcaaagtgatcaacgccatcatcaagaag tacggcctgcccaacgacatcattatcgagctggcccgcgagaag aactccaaggacgcccagaaaatgatcaacgagatgcagaagcggaaccggcagaccaac gagcggatcgaggaaatcatccggaccaccggcaaagag aacgccaagtacctgatcgagaagatcaagctgcacgacatgcaggaaggcaagtgcctg tacagcctggaagccatccctctggaagatctgctgaacaaccc cttcaactatgaggtggaccacatcatccccagaagcgtgtccttcgacaacagcttcaa caacaaggtgctcgtgaagcaggaagaagccagcaagaagggca accggaccccattccagtacctgagcagcagcgacagcaagatcagctacgaaaccttca agaagcacatcctgaatctggccaagggcaagggcagaatcag caagaccaagaaagagtatctgctggaagaacgggacatcaacaggttctccgtgcagaa agacttcatcaaccggaacctggtggataccagatacgccacca gaggcctgatgaacctgctgcggagctacttcagagtgaacaacctggacgtgaaagtga agtccatcaatggcggcttcaccagctttctgcggcggaagtggaa gtttaagaaagagcggaacaaggggtacaagcaccacgccgaggacgccctgatcattgc caacgccgatttcatcttcaaagagtggaagaaactggacaag gccaaaaaagtgatggaaaaccagatgttcgaggaaaagcaggccgagagcatgcccgag atcgaaaccgagcaggagtacaaagagatcttcatcacccc ccaccagatcaagcacattaaggacttcaaggactacaagtacagccaccgggtggacaa gaagcctaatagagagctgattaacgacaccctgtactccaccc ggaaggacgacaagggcaacaccctgatcgtgaacaatctgaacggcctgtacgacaagg acaatgacaagctgaaaaagctgatcaacaagagccccgaa aagctgctgatgtaccaccacgacccccagacctaccagaaactgaagctgattatggaa cagtacggcgacgagaagaatcccctgtacaagtactacgagga aaccgggaactacctgaccaagtactccaaaaaggacaacggccccgtgatcaagaagat taagtattacggcaacaaactgaacgcccatctggacatcacc gacgactaccccaacagcagaaacaaggtcgtgaagctgtccctgaagccctacagattc gacgtgtacctggacaatggcgtgtacaagttcgtgaccgtgaag aatctggatgtgatcaaaaaagaaaactactacgaagtgaatagcaagtgctatgaggaa gctaagaagctgaagaagatcagcaaccaggccgagtttatcgc ctccttctacaacaacgatctgatcaagatcaacggcgagctgtatagagtgatcggcgt gaacaacgacctgctgaaccggatcgaagtgaacatgatcgacatc acctaccgcgagtacctggaaaacatgaacgacaagaggccccccaggatcattaagaca atcgcctccaagacccagagcattaagaagtacagcacagac attctgggcaacctgtatgaagtgaaatctaagaagcaccctcagatcatcaaaaagggc aaaaggccggcggccacgaaaaaggccggccaggcaaaaaa gaaaaagggatccgaggccagcggttccggacgggctgacgcattggacgattttgatct ggatatgctgggaagtgacgccctcgatgattttgaccttgacatgctt ggttcggatgcccttgatgactttgacctcgacatgctcggcagtgacgcccttgatgat ttcgacctggacatgctgattaactcaagatgatctagacatatggatatct gactagtctcgagtttattgcagcttataatggttacaaataaagcaatagcatcacaaa tttcacaaataaagcatttttttcactggaccgagcggccgcaggaaccc ctagtgatggagttggccactccctctctgcgcgctcgctcgctcactgaggccgggcga ccaaaggtcgcccgacgcccgggctttgcccgggcggcctcagtga gcgagcgagcgcgcagctgcctgcaggggcgcctgatgcggtattttctccttacgcatc tgtgcggtatttcacaccgcatacgtcaaagcaaccatagtacgcgcc ctgtagcggcgcattaagcgcggcgggtgtggtggttacgcgcagcgtgaccgctacact tgccagcgccctagcgcccgctcctttcgctttcttcccttcctttctcgcc acgttcgccggctttccccgtcaagctctaaatcgggggctccctttagggttccgattt agtgctttacggcacctcgaccccaaaaaacttgatttgggtgatggttcac gtagtgggccatcgccctgatagacggtttttcgccctttgacgttggagtccacgttct ttaatagtggactcttgttccaaactggaacaacactcaaccctatctcgggc tattcttttgatttataagggattttgccgatttcggcctattggttaaaaaatgagctg atttaacaaaaatttaacgcgaattttaacaaaatattaacgtttacaattttatggt gcactctcagtacaatctgctctgatgccgcatagttaagccagccccgacacccgccaa cacccgctgacgcgccctgacgggcttgtctgctcccggcatccgctt acagacaagctgtgaccgtctccgggagctgcatgtgtcagaggttttcaccgtcatcac cgaaacgcgcgagacgaaagggcctcgtgatacgcctatttttatagg ttaatgtcatgataataatggtttcttagacgtcaggtggcacttttcggggaaatgtgc gcggaacccctatttgtttatttttctaaatacattcaaatatgtatccgctcatg agacaataaccctgataaatgcttcaataatattgaaaaaggaagagtatgagtattcaa catttccgtgtcgcccttattcccttttttgcggcattttgccttcctgtttttgct cacccagaaacgctggtgaaagtaaaagatgctgaagatcagttgggtgcacgagtgggt tacatcgaactggatctcaacagcggtaagatccttgagagttttcg ccccgaagaacgttttccaatgatgagcacttttaaagttctgctatgtggcgcggtatt atcccgtattgacgccgggcaagagcaactcggtcgccgcatacactatt ctcagaatgacttggttgagtactcaccagtcacagaaaagcatcttacggatggcatga cagtaagagaattatgcagtgctgccataaccatgagtgataacactg cggccaacttacttctgacaacgatcggaggaccgaaggagctaaccgcttttttgcaca acatgggggatcatgtaactcgccttgatcgttgggaaccggagctga atgaagccataccaaacgacgagcgtgacaccacgatgcctgtagcaatggcaacaacgt tgcgcaaactattaactggcgaactacttactctagcttcccggca acaattaatagactggatggaggcggataaagttgcaggaccacttctgcgctcggccct tccggctggctggtttattgctgataaatctggagccggtgagcgtggg tctcgcggtatcattgcagcactggggccagatggtaagccctcccgtatcgtagttatc tacacgacggggagtcaggcaactatggatgaacgaaatagacagat cgctgagataggtgcctcactgattaagcattggtaactgtcagaccaagtttactcata tatactttagattgatttaaaacttcatttttaatttaaaaggatctaggtgaag atcctttttgataatctcatgaccaaaatcccttaacgtgagttttcgttccactgagcg tcagaccccgtagaaaagatcaaaggatcttcttgagatcctttttttctgcgcg taatctgctgcttgcaaacaaaaaaaccaccgctaccagcggtggtttgtttgccggatc aagagctaccaactctttttccgaaggtaactggcttcagcagagcgca gataccaaatactgtccttctagtgtagccgtagttaggccaccacttcaagaactctgt agcaccgcctacatacctcgctctgctaatcctgttaccagtggctgctgcc agtggcgataagtcgtgtcttaccgggttggactcaagacgatagttaccggataaggcg cagcggtcgggctgaacggggggttcgtgcacacagcccagcttgg agcgaacgacctacaccgaactgagatacctacagcgtgagctatgagaaagcgccacgc ttcccgaagggagaaaggcggacaggtatccggtaagcggca gggtcggaacaggagagcgcacgagggagcttccagggggaaacgcctggtatctttata gtcctgtcgggtttcgccacctctgacttgagcgtcgatttttgtgatg ctcgtcaggggggcggagcctatggaaaaacgccagcaacgcggcctttttacggttcct ggccttttgctggccttttgctcacatgt pAAV-U6gRNA(Kcnq 2-sa sgRNA6)-CMV-sadCas9-VP64 used in in vitro experiments (SEQ ID NO: 134) cctgcaggcagctgcgcgctcgctcgctcactgaggccgcccgggcaaagcccgggcgtc gggcgacctttggtcgcccggcctcagtgagcgagcgagcgcg cagagagggagtggccaactccatcactaggggttcctgcggccgcacgcgtggtaccga gggcctatttcccatgattccttcatatttgcatatacgatacaaggct gttagagagataattggaattaatttgactgtaaacacaaagatattagtacaaaatacg tgacgtagaaagtaataatttcttgggtagtttgcagttttaaaattatgtttt aaaatggactatcatatgcttaccgtaacttgaaagtatttcgatttcttggctttatat atcttgtggaaaggacgaaacaccTCCTAGCCCGGTAATCCTT GAgttttagtactctggaaacagaatctactaaaacaaggcaaaatgccgtgtttatctc gtcaacttgttggcgagatttttgcgacgcgtggagttccgcgttacataa cttacggtaaatggcccgcctggctgaccgcccaacgacccccgcccattgacgtcaata atgacgtatgttcccatagtaacgccaatagggactttccattgacgtc aatgggtggagtatttacggtaaactgcccacttggcagtacatcaagtgtatcatatgc caagtacgccccctattgacgtcaatgacggtaaatggcccgcctggca ttatgcccagtacatgaccttatgggactttcctacttggcagtacatctacgtattagt catcgctattaccatggtgatgcggttttggcagtacatcaatgggcgtggata gcggtttgactcacggggatttccaagtctccaccccattgacgtcaatgggagtttgtt ttggcaccaaaatcaacgggactttccaaaatgtcgtaacaactccgccc cattgacgcaaatgggcggtaggcgtgtacggtgggaggtctatataagcagagctcgtt tagtgaaccgtcagatcgcctggagacgccatccacgctgttttgacc tccatagaagacaccgGAATTCGGTACCACCGGTgccaccatggccccaaagaagaagcg gaaggtcggtatccacggagtcccagcagccaag cggaactacatcctgggcctggccatcggcatcaccagcgtgggctacggcatcatcgac tacgagacacgggacgtgatcgatgccggcgtgcggctgttcaaa gaggccaacgtggaaaacaacgagggcaggcggagcaagagaggcgccagaaggctgaag cggcggaggcggcatagaatccagagagtgaagaagct gctgttcgactacaacctgctgaccgaccacagcgagctgagcggcatcaacccctacga ggccagagtgaagggcctgagccagaagctgagcgaggaaga gttctctgccgccctgctgcacctggccaagagaagaggcgtgcacaacgtgaacgaggt ggaagaggacaccggcaacgagctgtccaccaaagagcagat cagccggaacagcaaggccctggaagagaaatacgtggccgaactgcagctggaacggct gaagaaagacggcgaagtgcggggcagcatcaacagattc aagaccagcgactacgtgaaagaagccaaacagctgctgaaggtgcagaaggcctaccac cagctggaccagagcttcatcgacacctacatcgacctgctgg aaacccggcggacctactatgagggacctggcgagggcagccccttcggctggaaggaca tcaaagaatggtacgagatgctgatgggccactgcacctacttc cccgaggaactgcggagcgtgaagtacgcctacaacgccgacctgtacaacgccctgaac gacctgaacaatctcgtgatcaccagggacgagaacgagaag ctggaatattacgagaagttccagatcatcgagaacgtgttcaagcagaagaagaagccc accctgaagcagatcgccaaagaaatcctcgtgaacgaagagg atattaagggctacagagtgaccagcaccggcaagcccgagttcaccaacctgaaggtgt accacgacatcaaggacattaccgcccggaaagagattattgag aacgccgagctgctggatcagattgccaagatcctgaccatctaccagagcagcgaggac atccaggaagaactgaccaatctgaactccgagctgacccagga agagatcgagcagatctctaatctgaagggctataccggcacccacaacctgagcctgaa ggccatcaacctgatcctggacgagctgtggcacaccaacgaca accagatcgctatcttcaaccggctgaagctggtgcccaagaaggtggacctgtcccagc agaaagagatccccaccaccctggtggacgacttcatcctgagccc cgtcgtgaagagaagcttcatccagagcatcaaagtgatcaacgccatcatcaagaagta cggcctgcccaacgacatcattatcgagctggcccgcgagaaga actccaaggacgcccagaaaatgatcaacgagatgcagaagcggaaccggcagaccaacg agcggatcgaggaaatcatccggaccaccggcaaagaga acgccaagtacctgatcgagaagatcaagctgcacgacatgcaggaaggcaagtgcctgt acagcctggaagccatccctctggaagatctgctgaacaacccct tcaactatgaggtggaccacatcatccccagaagcgtgtccttcgacaacagcttcaaca acaaggtgctcgtgaagcaggaagaagccagcaagaagggcaa ccggaccccattccagtacctgagcagcagcgacagcaagatcagctacgaaaccttcaa gaagcacatcctgaatctggccaagggcaagggcagaatcagc aagaccaagaaagagtatctgctggaagaacgggacatcaacaggttctccgtgcagaaa gacttcatcaaccggaacctggtggataccagatacgccaccag aggcctgatgaacctgctgcggagctacttcagagtgaacaacctggacgtgaaagtgaa gtccatcaatggcggcttcaccagctttctgcggcggaagtggaag tttaagaaagagcggaacaaggggtacaagcaccacgccgaggacgccctgatcattgcc aacgccgatttcatcttcaaagagtggaagaaactggacaagg ccaaaaaagtgatggaaaaccagatgttcgaggaaaagcaggccgagagcatgcccgaga tcgaaaccgagcaggagtacaaagagatcttcatcacccccc accagatcaagcacattaaggacttcaaggactacaagtacagccaccgggtggacaaga agcctaatagagagctgattaacgacaccctgtactccacccgg aaggacgacaagggcaacaccctgatcgtgaacaatctgaacggcctgtacgacaaggac aatgacaagctgaaaaagctgatcaacaagagccccgaaaa gctgctgatgtaccaccacgacccccagacctaccagaaactgaagctgattatggaaca gtacggcgacgagaagaatcccctgtacaagtactacgaggaaa ccgggaactacctgaccaagtactccaaaaaggacaacggccccgtgatcaagaagatta agtattacggcaacaaactgaacgcccatctggacatcaccgac gactaccccaacagcagaaacaaggtcgtgaagctgtccctgaagccctacagattcgac gtgtacctggacaatggcgtgtacaagttcgtgaccgtgaagaatc tggatgtgatcaaaaaagaaaactactacgaagtgaatagcaagtgctatgaggaagcta agaagctgaagaagatcagcaaccaggccgagtttatcgcctcct tctacaacaacgatctgatcaagatcaacggcgagctgtatagagtgatcggcgtgaaca acgacctgctgaaccggatcgaagtgaacatgatcgacatcaccta ccgcgagtacctggaaaacatgaacgacaagaggccccccaggatcattaagacaatcgc ctccaagacccagagcattaagaagtacagcacagacattctg ggcaacctgtatgaagtgaaatctaagaagcaccctcagatcatcaaaaagggcaaaagg ccggcggccacgaaaaaggccggccaggcaaaaaagaaaa agggatccgaggccagcggttccggacgggctgacgcattggacgattttgatctggata tgctgggaagtgacgccctcgatgattttgaccttgacatgcttggttcg gatgcccttgatgactttgacctcgacatgctcggcagtgacgcccttgatgatttcgac ctggacatgctgattaactcaagatgatctagacatatggatatctgactag tctcgagtttattgcagcttataatggttacaaataaagcaatagcatcacaaatttcac aaataaagcatttttttcactggaccgagcggccgcaggaacccctagtg atggagttggccactccctctctgcgcgctcgctcgctcactgaggccgggcgaccaaag gtcgcccgacgcccgggctttgcccgggcggcctcagtgagcgag cgagcgcgcagctgcctgcaggggcgcctgatgcggtattttctccttacgcatctgtgc ggtatttcacaccgcatacgtcaaagcaaccatagtacgcgccctgtag cggcgcattaagcgcggcgggtgtggtggttacgcgcagcgtgaccgctacacttgccag cgccctagcgcccgctcctttcgctttcttcccttcctttctcgccacgttc gccggctttccccgtcaagctctaaatcgggggctccctttagggttccgatttagtgct ttacggcacctcgaccccaaaaaacttgatttgggtgatggttcacgtagtg ggccatcgccctgatagacggtttttcgccctttgacgttggagtccacgttctttaata gtggactcttgttccaaactggaacaacactcaaccctatctcgggctattcttt tgatttataagggattttgccgatttcggcctattggttaaaaaatgagctgatttaaca aaaatttaacgcgaattttaacaaaatattaacgtttacaattttatggtgcact ctcagtacaatctgctctgatgccgcatagttaagccagccccgacacccgccaacaccc gctgacgcgccctgacgggcttgtctgctcccggcatccgcttacag acaagctgtgaccgtctccgggagctgcatgtgtcagaggttttcaccgtcatcaccgaa acgcgcgagacgaaagggcctcgtgatacgcctatttttataggttaat gtcatgataataatggtttcttagacgtcaggtggcacttttcggggaaatgtgcgcgga acccctatttgtttatttttctaaatacattcaaatatgtatccgctcatgagac aataaccctgataaatgcttcaataatattgaaaaaggaagagtatgagtattcaacatt tccgtgtcgcccttattcccttttttgcggcattttgccttcctgtttttgctcacc cagaaacgctggtgaaagtaaaagatgctgaagatcagttgggtgcacgagtgggttaca tcgaactggatctcaacagcggtaagatccttgagagttttcgcccc gaagaacgttttccaatgatgagcacttttaaagttctgctatgtggcgcggtattatcc cgtattgacgccgggcaagagcaactcggtcgccgcatacactattctcag aatgacttggttgagtactcaccagtcacagaaaagcatcttacggatggcatgacagta agagaattatgcagtgctgccataaccatgagtgataacactgcggc caacttacttctgacaacgatcggaggaccgaaggagctaaccgcttttttgcacaacat gggggatcatgtaactcgccttgatcgttgggaaccggagctgaatga agccataccaaacgacgagcgtgacaccacgatgcctgtagcaatggcaacaacgttgcg caaactattaactggcgaactacttactctagcttcccggcaacaa ttaatagactggatggaggcggataaagttgcaggaccacttctgcgctcggcccttccg gctggctggtttattgctgataaatctggagccggtgagcgtgggtctcg cggtatcattgcagcactggggccagatggtaagccctcccgtatcgtagttatctacac gacggggagtcaggcaactatggatgaacgaaatagacagatcgct gagataggtgcctcactgattaagcattggtaactgtcagaccaagtttactcatatata ctttagattgatttaaaacttcatttttaatttaaaaggatctaggtgaagatcc tttttgataatctcatgaccaaaatcccttaacgtgagttttcgttccactgagcgtcag accccgtagaaaagatcaaaggatcttcttgagatcctttttttctgcgcgtaat ctgctgcttgcaaacaaaaaaaccaccgctaccagcggtggtttgtttgccggatcaaga gctaccaactctttttccgaaggtaactggcttcagcagagcgcagat accaaatactgtccttctagtgtagccgtagttaggccaccacttcaagaactctgtagc accgcctacatacctcgctctgctaatcctgttaccagtggctgctgccagt ggcgataagtcgtgtcttaccgggttggactcaagacgatagttaccggataaggcgcag cggtcgggctgaacggggggttcgtgcacacagcccagcttggag cgaacgacctacaccgaactgagatacctacagcgtgagctatgagaaagcgccacgctt cccgaagggagaaaggcggacaggtatccggtaagcggcagg gtcggaacaggagagcgcacgagggagcttccagggggaaacgcctggtatctttatagt cctgtcgggtttcgccacctctgacttgagcgtcgatttttgtgatgctc gtcaggggggcggagcctatggaaaaacgccagcaacgcggcctttttacggttcctggc cttttgctggccttttgctcacatgt pAAV-U6gRNA(Kcnq 3-sa sgRNA3)-CMV-sadCas9-VP64 used in in vitro experiments (SEQ ID NO: 135) cctgcaggcagctgcgcgctcgctcgctcactgaggccgcccgggcaaagcccgggcgtc gggcgacctttggtcgcccggcctcagtgagcgagcgagcgcg cagagagggagtggccaactccatcactaggggttcctgcggccgcacgcgtggtaccga gggcctatttcccatgattccttcatatttgcatatacgatacaaggct gttagagagataattggaattaatttgactgtaaacacaaagatattagtacaaaatacg tgacgtagaaagtaataatttcttgggtagtttgcagttttaaaattatgtttt aaaatggactatcatatgcttaccgtaacttgaaagtatttcgatttcttggctttatat atcttgtggaaaggacgaaacaccgCTACTGCCGCTGCAGCGG GGCgttttagtactctggaaacagaatctactaaaacaaggcaaaatgccgtgtttatct cgtcaacttgttggcgagatttttgcgacgcgtggagttccgcgttacat aacttacggtaaatggcccgcctggctgaccgcccaacgacccccgcccattgacgtcaa taatgacgtatgttcccatagtaacgccaatagggactttccattgac gtcaatgggtggagtatttacggtaaactgcccacttggcagtacatcaagtgtatcata tgccaagtacgccccctattgacgtcaatgacggtaaatggcccgcctg gcattatgcccagtacatgaccttatgggactttcctacttggcagtacatctacgtatt agtcatcgctattaccatggtgatgcggttttggcagtacatcaatgggcgtg gatagcggtttgactcacggggatttccaagtctccaccccattgacgtcaatgggagtt tgttttggcaccaaaatcaacgggactttccaaaatgtcgtaacaactcc gccccattgacgcaaatgggcggtaggcgtgtacggtgggaggtctatataagcagagct cgtttagtgaaccgtcagatcgcctggagacgccatccacgctgtttt gacctccatagaagacaccgGAATTCGGTACCACCGGTgccaccatggccccaaagaaga agcggaaggtcggtatccacggagtcccagcagc caagcggaactacatcctgggcctggccatcggcatcaccagcgtgggctacggcatcat cgactacgagacacgggacgtgatcgatgccggcgtgcggctgtt caaagaggccaacgtggaaaacaacgagggcaggcggagcaagagaggcgccagaaggct gaagcggcggaggcggcatagaatccagagagtgaag aagctgctgttcgactacaacctgctgaccgaccacagcgagctgagcggcatcaacccc tacgaggccagagtgaagggcctgagccagaagctgagcgagg aagagttctctgccgccctgctgcacctggccaagagaagaggcgtgcacaacgtgaacg aggtggaagaggacaccggcaacgagctgtccaccaaagagc agatcagccggaacagcaaggccctggaagagaaatacgtggccgaactgcagctggaac ggctgaagaaagacggcgaagtgcggggcagcatcaacag attcaagaccagcgactacgtgaaagaagccaaacagctgctgaaggtgcagaaggccta ccaccagctggaccagagcttcatcgacacctacatcgacctgc tggaaacccggcggacctactatgagggacctggcgagggcagccccttcggctggaagg acatcaaagaatggtacgagatgctgatgggccactgcacctac ttccccgaggaactgcggagcgtgaagtacgcctacaacgccgacctgtacaacgccctg aacgacctgaacaatctcgtgatcaccagggacgagaacgaga agctggaatattacgagaagttccagatcatcgagaacgtgttcaagcagaagaagaagc ccaccctgaagcagatcgccaaagaaatcctcgtgaacgaaga ggatattaagggctacagagtgaccagcaccggcaagcccgagttcaccaacctgaaggt gtaccacgacatcaaggacattaccgcccggaaagagattattg agaacgccgagctgctggatcagattgccaagatcctgaccatctaccagagcagcgagg acatccaggaagaactgaccaatctgaactccgagctgacccag gaagagatcgagcagatctctaatctgaagggctataccggcacccacaacctgagcctg aaggccatcaacctgatcctggacgagctgtggcacaccaacga caaccagatcgctatcttcaaccggctgaagctggtgcccaagaaggtggacctgtccca gcagaaagagatccccaccaccctggtggacgacttcatcctgag ccccgtcgtgaagagaagcttcatccagagcatcaaagtgatcaacgccatcatcaagaa gtacggcctgcccaacgacatcattatcgagctggcccgcgagaa gaactccaaggacgcccagaaaatgatcaacgagatgcagaagcggaaccggcagaccaa cgagcggatcgaggaaatcatccggaccaccggcaaaga gaacgccaagtacctgatcgagaagatcaagctgcacgacatgcaggaaggcaagtgcct gtacagcctggaagccatccctctggaagatctgctgaacaacc ccttcaactatgaggtggaccacatcatccccagaagcgtgtccttcgacaacagcttca acaacaaggtgctcgtgaagcaggaagaagccagcaagaagggc aaccggaccccattccagtacctgagcagcagcgacagcaagatcagctacgaaaccttc aagaagcacatcctgaatctggccaagggcaagggcagaatca gcaagaccaagaaagagtatctgctggaagaacgggacatcaacaggttctccgtgcaga aagacttcatcaaccggaacctggtggataccagatacgccacc agaggcctgatgaacctgctgcggagctacttcagagtgaacaacctggacgtgaaagtg aagtccatcaatggcggcttcaccagctttctgcggcggaagtgga agtttaagaaagagcggaacaaggggtacaagcaccacgccgaggacgccctgatcattg ccaacgccgatttcatcttcaaagagtggaagaaactggacaa ggccaaaaaagtgatggaaaaccagatgttcgaggaaaagcaggccgagagcatgcccga gatcgaaaccgagcaggagtacaaagagatcttcatcaccc cccaccagatcaagcacattaaggacttcaaggactacaagtacagccaccgggtggaca agaagcctaatagagagctgattaacgacaccctgtactccacc cggaaggacgacaagggcaacaccctgatcgtgaacaatctgaacggcctgtacgacaag gacaatgacaagctgaaaaagctgatcaacaagagccccga aaagctgctgatgtaccaccacgacccccagacctaccagaaactgaagctgattatgga acagtacggcgacgagaagaatcccctgtacaagtactacgagg aaaccgggaactacctgaccaagtactccaaaaaggacaacggccccgtgatcaagaaga ttaagtattacggcaacaaactgaacgcccatctggacatcac cgacgactaccccaacagcagaaacaaggtcgtgaagctgtccctgaagccctacagatt cgacgtgtacctggacaatggcgtgtacaagttcgtgaccgtgaa gaatctggatgtgatcaaaaaagaaaactactacgaagtgaatagcaagtgctatgagga agctaagaagctgaagaagatcagcaaccaggccgagtttatcg cctccttctacaacaacgatctgatcaagatcaacggcgagctgtatagagtgatcggcg tgaacaacgacctgctgaaccggatcgaagtgaacatgatcgacat cacctaccgcgagtacctggaaaacatgaacgacaagaggccccccaggatcattaagac aatcgcctccaagacccagagcattaagaagtacagcacaga cattctgggcaacctgtatgaagtgaaatctaagaagcaccctcagatcatcaaaaaggg caaaaggccggcggccacgaaaaaggccggccaggcaaaaa agaaaaagggatccgaggccagcggttccggacgggctgacgcattggacgattttgatc tggatatgctgggaagtgacgccctcgatgattttgaccttgacatgc ttggttcggatgcccttgatgactttgacctcgacatgctcggcagtgacgcccttgatg atttcgacctggacatgctgattaactcaagatgatctagacatatggatatc tgactagtctcgagtttattgcagcttataatggttacaaataaagcaatagcatcacaa atttcacaaataaagcatttttttcactggaccgagcggccgcaggaacc cctagtgatggagttggccactccctctctgcgcgctcgctcgctcactgaggccgggcg accaaaggtcgcccgacgcccgggctttgcccgggcggcctcagtg agcgagcgagcgcgcagctgcctgcaggggcgcctgatgcggtattttctccttacgcat ctgtgcggtatttcacaccgcatacgtcaaagcaaccatagtacgcgc cctgtagcggcgcattaagcgcggcgggtgtggtggttacgcgcagcgtgaccgctacac ttgccagcgccctagcgcccgctcctttcgctttcttcccttcctttctcgc cacgttcgccggctttccccgtcaagctctaaatcgggggctccctttagggttccgatt tagtgctttacggcacctcgaccccaaaaaacttgatttgggtgatggttca cgtagtgggccatcgccctgatagacggtttttcgccctttgacgttggagtccacgttc tttaatagtggactcttgttccaaactggaacaacactcaaccctatctcggg ctattcttttgatttataagggattttgccgatttcggcctattggttaaaaaatgagct gatttaacaaaaatttaacgcgaattttaacaaaatattaacgtttacaattttatg gtgcactctcagtacaatctgctctgatgccgcatagttaagccagccccgacacccgcc aacacccgctgacgcgccctgacgggcttgtctgctcccggcatccg cttacagacaagctgtgaccgtctccgggagctgcatgtgtcagaggttttcaccgtcat caccgaaacgcgcgagacgaaagggcctcgtgatacgcctatttttata ggttaatgtcatgataataatggtttcttagacgtcaggtggcacttttcggggaaatgt gcgcggaacccctatttgtttatttttctaaatacattcaaatatgtatccgctca tgagacaataaccctgataaatgcttcaataatattgaaaaaggaagagtatgagtattc aacatttccgtgtcgcccttattcccttttttgcggcattttgccttcctgtttttg ctcacccagaaacgctggtgaaagtaaaagatgctgaagatcagttgggtgcacgagtgg gttacatcgaactggatctcaacagcggtaagatccttgagagttttc gccccgaagaacgttttccaatgatgagcacttttaaagttctgctatgtggcgcggtat tatcccgtattgacgccgggcaagagcaactcggtcgccgcatacactat tctcagaatgacttggttgagtactcaccagtcacagaaaagcatcttacggatggcatg acagtaagagaattatgcagtgctgccataaccatgagtgataacact gcggccaacttacttctgacaacgatcggaggaccgaaggagctaaccgcttttttgcac aacatgggggatcatgtaactcgccttgatcgttgggaaccggagctg aatgaagccataccaaacgacgagcgtgacaccacgatgcctgtagcaatggcaacaacg ttgcgcaaactattaactggcgaactacttactctagcttcccggc aacaattaatagactggatggaggcggataaagttgcaggaccacttctgcgctcggccc ttccggctggctggtttattgctgataaatctggagccggtgagcgtgg gtctcgcggtatcattgcagcactggggccagatggtaagccctcccgtatcgtagttat ctacacgacggggagtcaggcaactatggatgaacgaaatagacag atcgctgagataggtgcctcactgattaagcattggtaactgtcagaccaagtttactca tatatactttagattgatttaaaacttcatttttaatttaaaaggatctaggtga agatcctttttgataatctcatgaccaaaatcccttaacgtgagttttcgttccactgag cgtcagaccccgtagaaaagatcaaaggatcttcttgagatcctttttttctgcg cgtaatctgctgcttgcaaacaaaaaaaccaccgctaccagcggtggtttgtttgccgga tcaagagctaccaactctttttccgaaggtaactggcttcagcagagcg cagataccaaatactgtccttctagtgtagccgtagttaggccaccacttcaagaactct gtagcaccgcctacatacctcgctctgctaatcctgttaccagtggctgct gccagtggcgataagtcgtgtcttaccgggttggactcaagacgatagttaccggataag gcgcagcggtcgggctgaacggggggttcgtgcacacagcccagct tggagcgaacgacctacaccgaactgagatacctacagcgtgagctatgagaaagcgcca cgcttcccgaagggagaaaggcggacaggtatccggtaagcg gcagggtcggaacaggagagcgcacgagggagcttccagggggaaacgcctggtatcttt atagtcctgtcgggtttcgccacctctgacttgagcgtcgatttttgtg atgctcgtcaggggggcggagcctatggaaaaacgccagcaacgcggcctttttacggtt cctggccttttgctggccttttgctcacatgt pAAV-U6gRNA(Kcna2-sa sgRNA2)-U6gRNA(Kcnj2-sa sgRNA1)-CMV-sadCas9-VP64 used in in vitro experiments (SEQ ID NO: 136) cctgcaggcagctgcgcgctcgctcgctcactgaggccgcccgggcaaagcccgggcgtc gggcgacctttggtcgcccggcctcagtgagcgagcgagcgcg cagagagggagtggccaactccatcactaggggttcctgcggccgcacgcgtgagggcct atttcccatgattccttcatatttgcatatacgatacaaggctgttaga gagataattggaattaatttgactgtaaacacaaagatattagtacaaaatacgtgacgt agaaagtaataatttcttgggtagtttgcagttttaaaattatgttttaaaatg gactatcatatgcttaccgtaacttgaaagtatttcgatttcttggctttatatatcttg tggaaaggacgaaacaccGCCCCAGCCGGCCCCTTTAATGtttt agtactctggaaacagaatctactaaaacaaggcaaaatgccgtgtttatctcgtcaact tgttggcgagatttttGGGCCCAAAAAATCTCGCCAACAA GTTGACGAGATAAACACGGCATTTTGCCTTGTTTTAGTAGATTCTGTTTCCAGAGTACTA AAACGAACCGCCATCA GGAGGAGGAGGTGTTTCGTCCTTTCCACAAGATATATAAAGCCAAGAAATCGAAATACTT TCAAGTTACGGTAAG CATATGATAGTCCATTTTAAAACATAATTTTAAAACTGCAAACTACCCAAGAAATTATTA CTTTCTACGTCACGTAT TTTGTACTAATATCTTTGTGTTTACAGTCAAATTAATTCCAATTATCTCTCTAACAGCCT TGTATCGTATATGCAAAT AT GAAGGAAT CAT GGGAAAT AGGCCCTCCTCCAcgcgtggagttccgcgttacataacttacggtaaatggcccgcctgg ctgaccgcccaac gacccccgcccattgacgtcaataatgacgtatgttcccatagtaacgccaatagggact ttccattgacgtcaatgggtggagtatttacggtaaactgcccacttggc agtacatcaagtgtatcatatgccaagtacgccccctattgacgtcaatgacggtaaatg gcccgcctggcattatgcccagtacatgaccttatgggactttcctacttg gcagtacatctacgtattagtcatcgctattaccatggtgatgcggttttggcagtacat caatgggcgtggatagcggtttgactcacggggatttccaagtctccacccc attgacgtcaatgggagtttgttttggcaccaaaatcaacgggactttccaaaatgtcgt aacaactccgccccattgacgcaaatgggcggtaggcgtgtacggtgg gaggtctatataagcagagctcgtttagtgaaccgtcagatcgcctggagacgccatcca cgctgttttgacctccatagaagacaccgGAATTCGGTACCA CCGGTgccaccatggccccaaagaagaagcggaaggtcggtatccacggagtcccagcag ccaagcggaactacatcctgggcctggccatcggcatcac cagcgtgggctacggcatcatcgactacgagacacgggacgtgatcgatgccggcgtgcg gctgttcaaagaggccaacgtggaaaacaacgagggcaggcg gagcaagagaggcgccagaaggctgaagcggcggaggcggcatagaatccagagagtgaa gaagctgctgttcgactacaacctgctgaccgaccacagcg agctgagcggcatcaacccctacgaggccagagtgaagggcctgagccagaagctgagcg aggaagagttctctgccgccctgctgcacctggccaagagaa gaggcgtgcacaacgtgaacgaggtggaagaggacaccggcaacgagctgtccaccaaag agcagatcagccggaacagcaaggccctggaagagaaat acgtggccgaactgcagctggaacggctgaagaaagacggcgaagtgcggggcagcatca acagattcaagaccagcgactacgtgaaagaagccaaaca gctgctgaaggtgcagaaggcctaccaccagctggaccagagcttcatcgacacctacat cgacctgctggaaacccggcggacctactatgagggacctggcg agggcagccccttcggctggaaggacatcaaagaatggtacgagatgctgatgggccact gcacctacttccccgaggaactgcggagcgtgaagtacgcctac aacgccgacctgtacaacgccctgaacgacctgaacaatctcgtgatcaccagggacgag aacgagaagctggaatattacgagaagttccagatcatcgagaa cgtgttcaagcagaagaagaagcccaccctgaagcagatcgccaaagaaatcctcgtgaa cgaagaggatattaagggctacagagtgaccagcaccggcaa gcccgagttcaccaacctgaaggtgtaccacgacatcaaggacattaccgcccggaaaga gattattgagaacgccgagctgctggatcagattgccaagatcct gaccatctaccagagcagcgaggacatccaggaagaactgaccaatctgaactccgagct gacccaggaagagatcgagcagatctctaatctgaagggctata ccggcacccacaacctgagcctgaaggccatcaacctgatcctggacgagctgtggcaca ccaacgacaaccagatcgctatcttcaaccggctgaagctggtgc ccaagaaggtggacctgtcccagcagaaagagatccccaccaccctggtggacgacttca tcctgagccccgtcgtgaagagaagcttcatccagagcatcaaa gtgatcaacgccatcatcaagaagtacggcctgcccaacgacatcattatcgagctggcc cgcgagaagaactccaaggacgcccagaaaatgatcaacgaga tgcagaagcggaaccggcagaccaacgagcggatcgaggaaatcatccggaccaccggca aagagaacgccaagtacctgatcgagaagatcaagctgca cgacatgcaggaaggcaagtgcctgtacagcctggaagccatccctctggaagatctgct gaacaaccccttcaactatgaggtggaccacatcatccccagaag cgtgtccttcgacaacagcttcaacaacaaggtgctcgtgaagcaggaagaagccagcaa gaagggcaaccggaccccattccagtacctgagcagcagcgac agcaagatcagctacgaaaccttcaagaagcacatcctgaatctggccaagggcaagggc agaatcagcaagaccaagaaagagtatctgctggaagaacgg gacatcaacaggttctccgtgcagaaagacttcatcaaccggaacctggtggataccaga tacgccaccagaggcctgatgaacctgctgcggagctacttcaga gtgaacaacctggacgtgaaagtgaagtccatcaatggcggcttcaccagctttctgcgg cggaagtggaagtttaagaaagagcggaacaaggggtacaagca ccacgccgaggacgccctgatcattgccaacgccgatttcatcttcaaagagtggaagaa actggacaaggccaaaaaagtgatggaaaaccagatgttcgagg aaaagcaggccgagagcatgcccgagatcgaaaccgagcaggagtacaaagagatcttca tcaccccccaccagatcaagcacattaaggacttcaaggact acaagtacagccaccgggtggacaagaagcctaatagagagctgattaacgacaccctgt actccacccggaaggacgacaagggcaacaccctgatcgtga acaatctgaacggcctgtacgacaaggacaatgacaagctgaaaaagctgatcaacaaga gccccgaaaagctgctgatgtaccaccacgacccccagaccta ccagaaactgaagctgattatggaacagtacggcgacgagaagaatcccctgtacaagta ctacgaggaaaccgggaactacctgaccaagtactccaaaaag gacaacggccccgtgatcaagaagattaagtattacggcaacaaactgaacgcccatctg gacatcaccgacgactaccccaacagcagaaacaaggtcgtga agctgtccctgaagccctacagattcgacgtgtacctggacaatggcgtgtacaagttcg tgaccgtgaagaatctggatgtgatcaaaaaagaaaactactacgaa gtgaatagcaagtgctatgaggaagctaagaagctgaagaagatcagcaaccaggccgag tttatcgcctccttctacaacaacgatctgatcaagatcaacggc gagctgtatagagtgatcggcgtgaacaacgacctgctgaaccggatcgaagtgaacatg atcgacatcacctaccgcgagtacctggaaaacatgaacgacaa gaggccccccaggatcattaagacaatcgcctccaagacccagagcattaagaagtacag cacagacattctgggcaacctgtatgaagtgaaatctaagaagc accctcagatcatcaaaaagggcaaaaggccggcggccacgaaaaaggccggccaggcaa aaaagaaaaagggatccgaggccagcggttccggacggg ctgacgcattggacgattttgatctggatatgctgggaagtgacgccctcgatgattttg accttgacatgcttggttcggatgcccttgatgactttgacctcgacatgctcg gcagtgacgcccttgatgatttcgacctggacatgctgattaactcaagatgatctagac atatggatatctgactagtctcgagtttattgcagcttataatggttacaaat aaagcaatagcatcacaaatttcacaaataaagcatttttttcactggaccgagcggccg caggaacccctagtgatggagttggccactccctctctgcgcgctcgct cgctcactgaggccgggcgaccaaaggtcgcccgacgcccgggctttgcccgggcggcct cagtgagcgagcgagcgcgcagctgcctgcaggggcgcctgat gcggtattttctccttacgcatctgtgcggtatttcacaccgcatacgtcaaagcaacca tagtacgcgccctgtagcggcgcattaagcgcggcgggtgtggtggttac gcgcagcgtgaccgctacacttgccagcgccctagcgcccgctcctttcgctttcttccc ttcctttctcgccacgttcgccggctttccccgtcaagctctaaatcggggg ctccctttagggttccgatttagtgctttacggcacctcgaccccaaaaaacttgatttg ggtgatggttcacgtagtgggccatcgccctgatagacggtttttcgccctttg acgttggagtccacgttctttaatagtggactcttgttccaaactggaacaacactcaac cctatctcgggctattcttttgatttataagggattttgccgatttcggcctattg gttaaaaaatgagctgatttaacaaaaatttaacgcgaattttaacaaaatattaacgtt tacaattttatggtgcactctcagtacaatctgctctgatgccgcatagttaa gccagccccgacacccgccaacacccgctgacgcgccctgacgggcttgtctgctcccgg catccgcttacagacaagctgtgaccgtctccgggagctgcatgtg tcagaggttttcaccgtcatcaccgaaacgcgcgagacgaaagggcctcgtgatacgcct atttttataggttaatgtcatgataataatggtttcttagacgtcaggtgg cacttttcggggaaatgtgcgcggaacccctatttgtttatttttctaaatacattcaaa tatgtatccgctcatgagacaataaccctgataaatgcttcaataatattgaaa aaggaagagtatgagtattcaacatttccgtgtcgcccttattcccttttttgcggcatt ttgccttcctgtttttgctcacccagaaacgctggtgaaagtaaaagatgctga agatcagttgggtgcacgagtgggttacatcgaactggatctcaacagcggtaagatcct tgagagttttcgccccgaagaacgttttccaatgatgagcacttttaaag ttctgctatgtggcgcggtattatcccgtattgacgccgggcaagagcaactcggtcgcc gcatacactattctcagaatgacttggttgagtactcaccagtcacagaa aagcatcttacggatggcatgacagtaagagaattatgcagtgctgccataaccatgagt gataacactgcggccaacttacttctgacaacgatcggaggaccga aggagctaaccgcttttttgcacaacatgggggatcatgtaactcgccttgatcgttggg aaccggagctgaatgaagccataccaaacgacgagcgtgacaccac gatgcctgtagcaatggcaacaacgttgcgcaaactattaactggcgaactacttactct agcttcccggcaacaattaatagactggatggaggcggataaagttgc aggaccacttctgcgctcggcccttccggctggctggtttattgctgataaatctggagc cggtgagcgtgggtctcgcggtatcattgcagcactggggccagatggta agccctcccgtatcgtagttatctacacgacggggagtcaggcaactatggatgaacgaa atagacagatcgctgagataggtgcctcactgattaagcattggtaa ctgtcagaccaagtttactcatatatactttagattgatttaaaacttcatttttaattt aaaaggatctaggtgaagatcctttttgataatctcatgaccaaaatcccttaacgt gagttttcgttccactgagcgtcagaccccgtagaaaagatcaaaggatcttcttgagat cctttttttctgcgcgtaatctgctgcttgcaaacaaaaaaaccaccgcta ccagcggtggtttgtttgccggatcaagagctaccaactctttttccgaaggtaactggc ttcagcagagcgcagataccaaatactgtccttctagtgtagccgtagtta ggccaccacttcaagaactctgtagcaccgcctacatacctcgctctgctaatcctgtta ccagtggctgctgccagtggcgataagtcgtgtcttaccgggttggactc aagacgatagttaccggataaggcgcagcggtcgggctgaacggggggttcgtgcacaca gcccagcttggagcgaacgacctacaccgaactgagataccta cagcgtgagctatgagaaagcgccacgcttcccgaagggagaaaggcggacaggtatccg gtaagcggcagggtcggaacaggagagcgcacgagggagc ttccagggggaaacgcctggtatctttatagtcctgtcgggtttcgccacctctgacttg agcgtcgatttttgtgatgctcgtcaggggggcggagcctatggaaaaacg ccagcaacgcggcctttttacggttcctggccttttgctggccttttgctcacatgt pAAV-U6gRNA(Kcna2-sa sgRNA2)-U6gRNA(Kcnj2-sa sgRNA2)-CMV-sadCas9-VP64 used in in vitro experiments (SEQ ID NO: 137) cctgcaggcagctgcgcgctcgctcgctcactgaggccgcccgggcaaagcccgggcgtc gggcgacctttggtcgcccggcctcagtgagcgagcgagcgcg cagagagggagtggccaactccatcactaggggttcctgcggccgcacgcgtgagggcct atttcccatgattccttcatatttgcatatacgatacaaggctgttaga gagataattggaattaatttgactgtaaacacaaagatattagtacaaaatacgtgacgt agaaagtaataatttcttgggtagtttgcagttttaaaattatgttttaaaatg gactatcatatgcttaccgtaacttgaaagtatttcgatttcttggctttatatatcttg tggaaaggacgaaacaccGCCCCAGCCGGCCCCTTTAATGtttt agtactctggaaacagaatctactaaaacaaggcaaaatgccgtgtttatctcgtcaact tgttggcgagatttttGGGCCCAAAAAATCTCGCCAACAA GTTGACGAGATAAACACGGCATTTTGCCTTGTTTTAGTAGATTCTGTTTCCAGAGTACTA AAACCCTGATGGCGG TTCCCGGGGCGGTGTTTCGTCCTTTCCACAAGATATATAAAGCCAAGAAATCGAAATACT TTCAAGTTACGGTAA GCATATGATAGTCCATTTTAAAACATAATTTTAAAACTGCAAACTACCCAAGAAATTATT ACTTTCTACGTCACGTA TTTTGTACTAATATCTTTGTGTTTACAGTCAAATTAATTCCAATTATCTCTCTAACAGCC TTGTATCGTATATGCAAA TAT GAAGGAAT CAT GGGAAAT AGGCCCTCCTCCAcgcgtggagttccgcgttacataacttacggtaaatggcccgcctgg ctgaccgccca acgacccccgcccattgacgtcaataatgacgtatgttcccatagtaacgccaataggga ctttccattgacgtcaatgggtggagtatttacggtaaactgcccacttg gcagtacatcaagtgtatcatatgccaagtacgccccctattgacgtcaatgacggtaaa tggcccgcctggcattatgcccagtacatgaccttatgggactttcctact tggcagtacatctacgtattagtcatcgctattaccatggtgatgcggttttggcagtac atcaatgggcgtggatagcggtttgactcacggggatttccaagtctccacc ccattgacgtcaatgggagtttgttttggcaccaaaatcaacgggactttccaaaatgtc gtaacaactccgccccattgacgcaaatgggcggtaggcgtgtacggtg ggaggtctatataagcagagctcgtttagtgaaccgtcagatcgcctggagacgccatcc acgctgttttgacctccatagaagacaccgGAATTCGGTACC ACCGGTgccaccatggccccaaagaagaagcggaaggtcggtatccacggagtcccagca gccaagcggaactacatcctgggcctggccatcggcatca ccagcgtgggctacggcatcatcgactacgagacacgggacgtgatcgatgccggcgtgc ggctgttcaaagaggccaacgtggaaaacaacgagggcaggc ggagcaagagaggcgccagaaggctgaagcggcggaggcggcatagaatccagagagtga agaagctgctgttcgactacaacctgctgaccgaccacagc gagctgagcggcatcaacccctacgaggccagagtgaagggcctgagccagaagctgagc gaggaagagttctctgccgccctgctgcacctggccaagaga agaggcgtgcacaacgtgaacgaggtggaagaggacaccggcaacgagctgtccaccaaa gagcagatcagccggaacagcaaggccctggaagagaaa tacgtggccgaactgcagctggaacggctgaagaaagacggcgaagtgcggggcagcatc aacagattcaagaccagcgactacgtgaaagaagccaaaca gctgctgaaggtgcagaaggcctaccaccagctggaccagagcttcatcgacacctacat cgacctgctggaaacccggcggacctactatgagggacctggcg agggcagccccttcggctggaaggacatcaaagaatggtacgagatgctgatgggccact gcacctacttccccgaggaactgcggagcgtgaagtacgcctac aacgccgacctgtacaacgccctgaacgacctgaacaatctcgtgatcaccagggacgag aacgagaagctggaatattacgagaagttccagatcatcgagaa cgtgttcaagcagaagaagaagcccaccctgaagcagatcgccaaagaaatcctcgtgaa cgaagaggatattaagggctacagagtgaccagcaccggcaa gcccgagttcaccaacctgaaggtgtaccacgacatcaaggacattaccgcccggaaaga gattattgagaacgccgagctgctggatcagattgccaagatcct gaccatctaccagagcagcgaggacatccaggaagaactgaccaatctgaactccgagct gacccaggaagagatcgagcagatctctaatctgaagggctata ccggcacccacaacctgagcctgaaggccatcaacctgatcctggacgagctgtggcaca ccaacgacaaccagatcgctatcttcaaccggctgaagctggtgc ccaagaaggtggacctgtcccagcagaaagagatccccaccaccctggtggacgacttca tcctgagccccgtcgtgaagagaagcttcatccagagcatcaaa gtgatcaacgccatcatcaagaagtacggcctgcccaacgacatcattatcgagctggcc cgcgagaagaactccaaggacgcccagaaaatgatcaacgaga tgcagaagcggaaccggcagaccaacgagcggatcgaggaaatcatccggaccaccggca aagagaacgccaagtacctgatcgagaagatcaagctgca cgacatgcaggaaggcaagtgcctgtacagcctggaagccatccctctggaagatctgct gaacaaccccttcaactatgaggtggaccacatcatccccagaag cgtgtccttcgacaacagcttcaacaacaaggtgctcgtgaagcaggaagaagccagcaa gaagggcaaccggaccccattccagtacctgagcagcagcgac agcaagatcagctacgaaaccttcaagaagcacatcctgaatctggccaagggcaagggc agaatcagcaagaccaagaaagagtatctgctggaagaacgg gacatcaacaggttctccgtgcagaaagacttcatcaaccggaacctggtggataccaga tacgccaccagaggcctgatgaacctgctgcggagctacttcaga gtgaacaacctggacgtgaaagtgaagtccatcaatggcggcttcaccagctttctgcgg cggaagtggaagtttaagaaagagcggaacaaggggtacaagca ccacgccgaggacgccctgatcattgccaacgccgatttcatcttcaaagagtggaagaa actggacaaggccaaaaaagtgatggaaaaccagatgttcgagg aaaagcaggccgagagcatgcccgagatcgaaaccgagcaggagtacaaagagatcttca tcaccccccaccagatcaagcacattaaggacttcaaggact acaagtacagccaccgggtggacaagaagcctaatagagagctgattaacgacaccctgt actccacccggaaggacgacaagggcaacaccctgatcgtga acaatctgaacggcctgtacgacaaggacaatgacaagctgaaaaagctgatcaacaaga gccccgaaaagctgctgatgtaccaccacgacccccagaccta ccagaaactgaagctgattatggaacagtacggcgacgagaagaatcccctgtacaagta ctacgaggaaaccgggaactacctgaccaagtactccaaaaag gacaacggccccgtgatcaagaagattaagtattacggcaacaaactgaacgcccatctg gacatcaccgacgactaccccaacagcagaaacaaggtcgtga agctgtccctgaagccctacagattcgacgtgtacctggacaatggcgtgtacaagttcg tgaccgtgaagaatctggatgtgatcaaaaaagaaaactactacgaa gtgaatagcaagtgctatgaggaagctaagaagctgaagaagatcagcaaccaggccgag tttatcgcctccttctacaacaacgatctgatcaagatcaacggc gagctgtatagagtgatcggcgtgaacaacgacctgctgaaccggatcgaagtgaacatg atcgacatcacctaccgcgagtacctggaaaacatgaacgacaa gaggccccccaggatcattaagacaatcgcctccaagacccagagcattaagaagtacag cacagacattctgggcaacctgtatgaagtgaaatctaagaagc accctcagatcatcaaaaagggcaaaaggccggcggccacgaaaaaggccggccaggcaa aaaagaaaaagggatccgaggccagcggttccggacggg ctgacgcattggacgattttgatctggatatgctgggaagtgacgccctcgatgattttg accttgacatgcttggttcggatgcccttgatgactttgacctcgacatgctcg gcagtgacgcccttgatgatttcgacctggacatgctgattaactcaagatgatctagac atatggatatctgactagtctcgagtttattgcagcttataatggttacaaat aaagcaatagcatcacaaatttcacaaataaagcatttttttcactggaccgagcggccg caggaacccctagtgatggagttggccactccctctctgcgcgctcgct cgctcactgaggccgggcgaccaaaggtcgcccgacgcccgggctttgcccgggcggcct cagtgagcgagcgagcgcgcagctgcctgcaggggcgcctgat gcggtattttctccttacgcatctgtgcggtatttcacaccgcatacgtcaaagcaacca tagtacgcgccctgtagcggcgcattaagcgcggcgggtgtggtggttac gcgcagcgtgaccgctacacttgccagcgccctagcgcccgctcctttcgctttcttccc ttcctttctcgccacgttcgccggctttccccgtcaagctctaaatcggggg ctccctttagggttccgatttagtgctttacggcacctcgaccccaaaaaacttgatttg ggtgatggttcacgtagtgggccatcgccctgatagacggtttttcgccctttg acgttggagtccacgttctttaatagtggactcttgttccaaactggaacaacactcaac cctatctcgggctattcttttgatttataagggattttgccgatttcggcctattg gttaaaaaatgagctgatttaacaaaaatttaacgcgaattttaacaaaatattaacgtt tacaattttatggtgcactctcagtacaatctgctctgatgccgcatagttaa gccagccccgacacccgccaacacccgctgacgcgccctgacgggcttgtctgctcccgg catccgcttacagacaagctgtgaccgtctccgggagctgcatgtg tcagaggttttcaccgtcatcaccgaaacgcgcgagacgaaagggcctcgtgatacgcct atttttataggttaatgtcatgataataatggtttcttagacgtcaggtgg cacttttcggggaaatgtgcgcggaacccctatttgtttatttttctaaatacattcaaa tatgtatccgctcatgagacaataaccctgataaatgcttcaataatattgaaa aaggaagagtatgagtattcaacatttccgtgtcgcccttattcccttttttgcggcatt ttgccttcctgtttttgctcacccagaaacgctggtgaaagtaaaagatgctga agatcagttgggtgcacgagtgggttacatcgaactggatctcaacagcggtaagatcct tgagagttttcgccccgaagaacgttttccaatgatgagcacttttaaag ttctgctatgtggcgcggtattatcccgtattgacgccgggcaagagcaactcggtcgcc gcatacactattctcagaatgacttggttgagtactcaccagtcacagaa aagcatcttacggatggcatgacagtaagagaattatgcagtgctgccataaccatgagt gataacactgcggccaacttacttctgacaacgatcggaggaccga aggagctaaccgcttttttgcacaacatgggggatcatgtaactcgccttgatcgttggg aaccggagctgaatgaagccataccaaacgacgagcgtgacaccac gatgcctgtagcaatggcaacaacgttgcgcaaactattaactggcgaactacttactct agcttcccggcaacaattaatagactggatggaggcggataaagttgc aggaccacttctgcgctcggcccttccggctggctggtttattgctgataaatctggagc cggtgagcgtgggtctcgcggtatcattgcagcactggggccagatggta agccctcccgtatcgtagttatctacacgacggggagtcaggcaactatggatgaacgaa atagacagatcgctgagataggtgcctcactgattaagcattggtaa ctgtcagaccaagtttactcatatatactttagattgatttaaaacttcatttttaattt aaaaggatctaggtgaagatcctttttgataatctcatgaccaaaatcccttaacgt gagttttcgttccactgagcgtcagaccccgtagaaaagatcaaaggatcttcttgagat cctttttttctgcgcgtaatctgctgcttgcaaacaaaaaaaccaccgcta ccagcggtggtttgtttgccggatcaagagctaccaactctttttccgaaggtaactggc ttcagcagagcgcagataccaaatactgtccttctagtgtagccgtagtta ggccaccacttcaagaactctgtagcaccgcctacatacctcgctctgctaatcctgtta ccagtggctgctgccagtggcgataagtcgtgtcttaccgggttggactc aagacgatagttaccggataaggcgcagcggtcgggctgaacggggggttcgtgcacaca gcccagcttggagcgaacgacctacaccgaactgagataccta cagcgtgagctatgagaaagcgccacgcttcccgaagggagaaaggcggacaggtatccg gtaagcggcagggtcggaacaggagagcgcacgagggagc ttccagggggaaacgcctggtatctttatagtcctgtcgggtttcgccacctctgacttg agcgtcgatttttgtgatgctcgtcaggggggcggagcctatggaaaaacg ccagcaacgcggcctttttacggttcctggccttttgctggccttttgctcacatgt pAAV-U6gRNA(Kcnq 2-sa sgRNA6)-U6gRNA(Kcnq 3-sa sgRNA3)-CMV-sadCas9-VP64 used in in vitro experiments (SEQ ID NO: 138) cctgcaggcagctgcgcgctcgctcgctcactgaggccgcccgggcaaagcccgggcgtc gggcgacctttggtcgcccggcctcagtgagcgagcgagcgcg cagagagggagtggccaactccatcactaggggttcctgcggccgcacgcgtggaggagg gcctatttcccatgattccttcatatttgcatatacgatacaaggctgt tagagagataattggaattaatttgactgtaaacacaaagatattagtacaaaatacgtg acgtagaaagtaataatttcttgggtagtttgcagttttaaaattatgttttaa aatggactatcatatgcttaccgtaacttgaaagtatttcgatttcttggctttatatat cttgtggaaaggacgaaacaccTCCTAGCCCGGTAATCCTTGA gttttagtactctggaaacagaatctactaaaacaaggcaaaatgccgtgtttatctcgt caacttgttggcgagattttttgggcccgaggagggcctatttcccatgattc cttcatatttgcatatacgatacaaggctgttagagagataattggaattaatttgactg taaacacaaagatattagtacaaaatacgtgacgtagaaagtaataatttct tgggtagtttgcagttttaaaattatgttttaaaatggactatcatatgcttaccgtaac ttgaaagtatttcgatttcttggctttatatatcttgtggaaaggacgaaacaccg CTACTGCCGCTGCAGCGGGGCgttttagtactctggaaacagaatctactaaaacaaggc aaaatgccgtgtttatctcgtcaacttgttggcgagattttt tacgcgtggagttccgcgttacataacttacggtaaatggcccgcctggctgaccgccca acgacccccgcccattgacgtcaataatgacgtatgttcccatagtaa cgccaatagggactttccattgacgtcaatgggtggagtatttacggtaaactgcccact tggcagtacatcaagtgtatcatatgccaagtacgccccctattgacgtc aatgacggtaaatggcccgcctggcattatgcccagtacatgaccttatgggactttcct acttggcagtacatctacgtattagtcatcgctattaccatggtgatgcggtt ttggcagtacatcaatgggcgtggatagcggtttgactcacggggatttccaagtctcca ccccattgacgtcaatgggagtttgttttggcaccaaaatcaacgggact ttccaaaatgtcgtaacaactccgccccattgacgcaaatgggcggtaggcgtgtacggt gggaggtctatataagcagagctcgtttagtgaaccgtcagatcgcct ggagacgccatccacgctgttttgacctccatagaagacaccggaattcggtaccaccgg tgccaccatggccccaaagaagaagcggaaggtcggtatccacg gagtcccagcagccaagcggaactacatcctgggcctggccatcggcatcaccagcgtgg gctacggcatcatcgactacgagacacgggacgtgatcgatgcc ggcgtgcggctgttcaaagaggccaacgtggaaaacaacgagggcaggcggagcaagaga ggcgccagaaggctgaagcggcggaggcggcatagaatc cagagagtgaagaagctgctgttcgactacaacctgctgaccgaccacagcgagctgagc ggcatcaacccctacgaggccagagtgaagggcctgagccag aagctgagcgaggaagagttctctgccgccctgctgcacctggccaagagaagaggcgtg cacaacgtgaacgaggtggaagaggacaccggcaacgagctg tccaccaaagagcagatcagccggaacagcaaggccctggaagagaaatacgtggccgaa ctgcagctggaacggctgaagaaagacggcgaagtgcggg gcagcatcaacagattcaagaccagcgactacgtgaaagaagccaaacagctgctgaagg tgcagaaggcctaccaccagctggaccagagcttcatcgaca cctacatcgacctgctggaaacccggcggacctactatgagggacctggcgagggcagcc ccttcggctggaaggacatcaaagaatggtacgagatgctgatg ggccactgcacctacttccccgaggaactgcggagcgtgaagtacgcctacaacgccgac ctgtacaacgccctgaacgacctgaacaatctcgtgatcaccagg gacgagaacgagaagctggaatattacgagaagttccagatcatcgagaacgtgttcaag cagaagaagaagcccaccctgaagcagatcgccaaagaaatc ctcgtgaacgaagaggatattaagggctacagagtgaccagcaccggcaagcccgagttc accaacctgaaggtgtaccacgacatcaaggacattaccgccc ggaaagagattattgagaacgccgagctgctggatcagattgccaagatcctgaccatct accagagcagcgaggacatccaggaagaactgaccaatctgaac tccgagctgacccaggaagagatcgagcagatctctaatctgaagggctataccggcacc cacaacctgagcctgaaggccatcaacctgatcctggacgagctg tggcacaccaacgacaaccagatcgctatcttcaaccggctgaagctggtgcccaagaag gtggacctgtcccagcagaaagagatccccaccaccctggtgga cgacttcatcctgagccccgtcgtgaagagaagcttcatccagagcatcaaagtgatcaa cgccatcatcaagaagtacggcctgcccaacgacatcattatcgag ctggcccgcgagaagaactccaaggacgcccagaaaatgatcaacgagatgcagaagcgg aaccggcagaccaacgagcggatcgaggaaatcatccgga ccaccggcaaagagaacgccaagtacctgatcgagaagatcaagctgcacgacatgcagg aaggcaagtgcctgtacagcctggaagccatccctctggaag atctgctgaacaaccccttcaactatgaggtggaccacatcatccccagaagcgtgtcct tcgacaacagcttcaacaacaaggtgctcgtgaagcaggaagaagc cagcaagaagggcaaccggaccccattccagtacctgagcagcagcgacagcaagatcag ctacgaaaccttcaagaagcacatcctgaatctggccaaggg caagggcagaatcagcaagaccaagaaagagtatctgctggaagaacgggacatcaacag gttctccgtgcagaaagacttcatcaaccggaacctggtggat accagatacgccaccagaggcctgatgaacctgctgcggagctacttcagagtgaacaac ctggacgtgaaagtgaagtccatcaatggcggcttcaccagctttc tgcggcggaagtggaagtttaagaaagagcggaacaaggggtacaagcaccacgccgagg acgccctgatcattgccaacgccgatttcatcttcaaagagtgg aagaaactggacaaggccaaaaaagtgatggaaaaccagatgttcgaggaaaagcaggcc gagagcatgcccgagatcgaaaccgagcaggagtacaaa gagatcttcatcaccccccaccagatcaagcacattaaggacttcaaggactacaagtac agccaccgggtggacaagaagcctaatagagagctgattaacga caccctgtactccacccggaaggacgacaagggcaacaccctgatcgtgaacaatctgaa cggcctgtacgacaaggacaatgacaagctgaaaaagctgatc aacaagagccccgaaaagctgctgatgtaccaccacgacccccagacctaccagaaactg aagctgattatggaacagtacggcgacgagaagaatcccctgt acaagtactacgaggaaaccgggaactacctgaccaagtactccaaaaaggacaacggcc ccgtgatcaagaagattaagtattacggcaacaaactgaacgc ccatctggacatcaccgacgactaccccaacagcagaaacaaggtcgtgaagctgtccct gaagccctacagattcgacgtgtacctggacaatggcgtgtacaa gttcgtgaccgtgaagaatctggatgtgatcaaaaaagaaaactactacgaagtgaatag caagtgctatgaggaagctaagaagctgaagaagatcagcaacc aggccgagtttatcgcctccttctacaacaacgatctgatcaagatcaacggcgagctgt atagagtgatcggcgtgaacaacgacctgctgaaccggatcgaagtg aacatgatcgacatcacctaccgcgagtacctggaaaacatgaacgacaagaggcccccc aggatcattaagacaatcgcctccaagacccagagcattaaga agtacagcacagacattctgggcaacctgtatgaagtgaaatctaagaagcaccctcaga tcatcaaaaagggcaaaaggccggcggccacgaaaaaggccg gccaggcaaaaaagaaaaagggatccgaggccagcggttccggacgggctgacgcattgg acgattttgatctggatatgctgggaagtgacgccctcgatgattt tgaccttgacatgcttggttcggatgcccttgatgactttgacctcgacatgctcggcag tgacgcccttgatgatttcgacctggacatgctgattaactcaagatgatcta gacatatggatatctgactagtctcgagtttattgcagcttataatggttacaaataaag caatagcatcacaaatttcacaaataaagcatttttttcactggaccgagcg gccgcaggaacccctagtgatggagttggccactccctctctgcgcgctcgctcgctcac tgaggccgggcgaccaaaggtcgcccgacgcccgggctttgcccgg gcggcctcagtgagcgagcgagcgcgcagctgcctgcaggggcgcctgatgcggtatttt ctccttacgcatctgtgcggtatttcacaccgcatacgtcaaagcaac catagtacgcgccctgtagcggcgcattaagcgcggcgggtgtggtggttacgcgcagcg tgaccgctacacttgccagcgccctagcgcccgctcctttcgctttctt cccttcctttctcgccacgttcgccggctttccccgtcaagctctaaatcgggggctccc tttagggttccgatttagtgctttacggcacctcgaccccaaaaaacttgattt gggtgatggttcacgtagtgggccatcgccctgatagacggtttttcgccctttgacgtt ggagtccacgttctttaatagtggactcttgttccaaactggaacaacactca accctatctcgggctattcttttgatttataagggattttgccgatttcggcctattggt taaaaaatgagctgatttaacaaaaatttaacgcgaattttaacaaaatattaac gtttacaattttatggtgcactctcagtacaatctgctctgatgccgcatagttaagcca gccccgacacccgccaacacccgctgacgcgccctgacgggcttgtctgc tcccggcatccgcttacagacaagctgtgaccgtctccgggagctgcatgtgtcagaggt tttcaccgtcatcaccgaaacgcgcgagacgaaagggcctcgtgata cgcctatttttataggttaatgtcatgataataatggtttcttagacgtcaggtggcact tttcggggaaatgtgcgcggaacccctatttgtttatttttctaaatacattcaaat atgtatccgctcatgagacaataaccctgataaatgcttcaataatattgaaaaaggaag agtatgagtattcaacatttccgtgtcgcccttattcccttttttgcggcatttt gccttcctgtttttgctcacccagaaacgctggtgaaagtaaaagatgctgaagatcagt tgggtgcacgagtgggttacatcgaactggatctcaacagcggtaagat ccttgagagttttcgccccgaagaacgttttccaatgatgagcacttttaaagttctgct atgtggcgcggtattatcccgtattgacgccgggcaagagcaactcggtcg ccgcatacactattctcagaatgacttggttgagtactcaccagtcacagaaaagcatct tacggatggcatgacagtaagagaattatgcagtgctgccataaccat gagtgataacactgcggccaacttacttctgacaacgatcggaggaccgaaggagctaac cgcttttttgcacaacatgggggatcatgtaactcgccttgatcgttgg gaaccggagctgaatgaagccataccaaacgacgagcgtgacaccacgatgcctgtagca atggcaacaacgttgcgcaaactattaactggcgaactacttact ctagcttcccggcaacaattaatagactggatggaggcggataaagttgcaggaccactt ctgcgctcggcccttccggctggctggtttattgctgataaatctggagc cggtgagcgtgggtctcgcggtatcattgcagcactggggccagatggtaagccctcccg tatcgtagttatctacacgacggggagtcaggcaactatggatgaac gaaatagacagatcgctgagataggtgcctcactgattaagcattggtaactgtcagacc aagtttactcatatatactttagattgatttaaaacttcatttttaatttaaaa ggatctaggtgaagatcctttttgataatctcatgaccaaaatcccttaacgtgagtttt cgttccactgagcgtcagaccccgtagaaaagatcaaaggatcttcttgag atcctttttttctgcgcgtaatctgctgcttgcaaacaaaaaaaccaccgctaccagcgg tggtttgtttgccggatcaagagctaccaactctttttccgaaggtaactgg cttcagcagagcgcagataccaaatactgtccttctagtgtagccgtagttaggccacca cttcaagaactctgtagcaccgcctacatacctcgctctgctaatcctgtt accagtggctgctgccagtggcgataagtcgtgtcttaccgggttggactcaagacgata gttaccggataaggcgcagcggtcgggctgaacggggggttcgtgc acacagcccagcttggagcgaacgacctacaccgaactgagatacctacagcgtgagcta tgagaaagcgccacgcttcccgaagggagaaaggcggacag gtatccggtaagcggcagggtcggaacaggagagcgcacgagggagcttccagggggaaa cgcctggtatctttatagtcctgtcgggtttcgccacctctgacttg agcgtcgatttttgtgatgctcgtcaggggggcggagcctatggaaaaacgccagcaacg cggcctttttacggttcctggccttttgctggccttttgctcacatgt