GOLDBAUM MAURO (BR)
CLAIMS What is claimed is: 1. A method of treating a subject, comprising: (a) selecting the subject if a predetermined pattern of fundus autofluorescence (FAF) is present in an eye of the subject at baseline; and (b) administering to the subject an effective amount of a therapy suitable for treating achromatopsia (ACHM). 2. A method of selecting and treating a subject predisposed to achromatopsia (ACHM), comprising: (a) selecting the subject if a predetermined pattern of fundus autofluorescence (FAF) is present in an eye of the subject at baseline; and (b) administering to the subject an effective amount of a therapy suitable for treating achromatopsia (ACHM). 3. A method of selecting and treating a subject having achromatopsia (ACHM) that is likely to be a visual field responder, comprising: (a) selecting the subject if a predetermined pattern of fundus autofluorescence (FAF) is present in an eye of the subject at baseline; and (b) administering to the subject an effective amount of a therapy suitable for treating achromatopsia (ACHM). 4. A method of reducing, inhibiting and/or preventing one or more symptoms of achromatopsia (ACHM) in a subject, comprising: (a) selecting the subject if a predetermined pattern of fundus autofluorescence (FAF) is present in an eye of the subject at baseline; and (b) administering to the subject an effective amount of a therapy suitable for treating achromatopsia (ACHM). 5. The method of any one of the preceding claims, further comprising classifying the pattern of fundus autofluorescence (FAF) in the eye of the subject as comprising central hypoautofluorescence (grade 0), normal autofluorescence (grade 1), or mild or strong hyperautofluorescence (grade 2). 6. The method of any one of the preceding claims, wherein: (a) a pattern of FAF comprising central hypoautofluorescence (grade 0) identifies a subject that is less likely to be a visual field responder; (b) a pattern of FAF comprising normal autofluorescence (grade 1) identifies a subject that is less likely to be a visual field responder; and/or (c) a pattern of FAF comprising mild or strong hyperautofluorescence (grade 2) identifies a subject that is more likely to be a visual field responder. 7. The method of any one of the preceding claims, wherein the predetermined pattern of fundus autofluorescence (FAF) is mild or strong hyperautofluorescence (grade 2). 8. The method of any one of the preceding claims, wherein the predetermined pattern of fundus autofluorescence (FAF) in the eye of the subject is obtained prior to or at the time of administration of the therapy suitable for treating achromatopsia (ACHM). 9. The method of any one of the preceding claims, further comprising monitoring the pattern of fundus autofluorescence (FAF) in the eye of the subject for a period of time after administration of the therapy suitable for treating achromatopsia (ACHM). 10. A method of treating a subject, comprising: (a) selecting the subject if a predetermined optical coherence tomography (OCT) central outer retina morphology is present in an eye of the subject at baseline; and (b) administering to the subject an effective amount of a therapy suitable for treating achromatopsia (ACHM). 11. A method of selecting and treating a subject predisposed to achromatopsia (ACHM), comprising: (a) selecting the subject if a predetermined optical coherence tomography (OCT) central outer retina morphology is present in an eye of the subject at baseline; and (b) administering to the subject an effective amount of a therapy suitable for treating achromatopsia (ACHM). 12. A method of selecting and treating a subject having achromatopsia (ACHM) that is more likely to be a visual field responder, comprising: (a) selecting the subject if a predetermined optical coherence tomography (OCT) central outer retina morphology is present in an eye of the subject at baseline; and (b) administering to the subject an effective amount of a therapy suitable for treating achromatopsia (ACHM). 13. A method of reducing, inhibiting and/or preventing one or more symptoms of achromatopsia (ACHM) in a subject, comprising: (a) selecting the subject if a predetermined optical coherence tomography (OCT) central outer retina morphology is present in an eye of the subject at baseline; and (b) administering to the subject an effective amount of a therapy suitable for treating achromatopsia (ACHM). 14. The method of any one of claims 10-13, further comprising classifying the optical coherence tomography (OCT) central outer retina morphology in the eye of the subject as comprising central absence of ellipsoid zone (EZ) line disturbance (grade 0), the presence of EZ line disturbance (grade 1), or the presence of empty optical space (grade 2). 15. The method of claim 14, wherein: (a) an OCT central outer retina morphology comprising the central absence of ellipsoid zone (EZ) line disturbance (grade 0) identifies a subject that is more likely to be a visual field responder; (b) an OCT central outer retina morphology comprising the presence of EZ line disturbance (grade 1) identifies a subject that is more likely to be a visual field responder; and/or (c) an OCT central outer retina morphology comprising the presence of empty optical space (grade 2) identifies a subject that is less likely to be a visual field responder. 16. The method of any one of claims 10-15, wherein the predetermined optical coherence tomography (OCT) central outer retina morphology is central absence of ellipsoid zone (EZ) line disturbance (grade 0) or presence of EZ line disturbance (grade 1). 17. The method of any one of claims 10-16, wherein the predetermined optical coherence tomography (OCT) central outer retina morphology in the eye of the subject is obtained prior to or at the time of administration of the therapy suitable for treating achromatopsia (ACHM). 18. The method of any one of claims 10-17, further comprising monitoring the optical coherence tomography (OCT) central outer retina morphology in the eye of the subject for a period of time after administration of the therapy suitable for treating achromatopsia (ACHM). 19. The method of any one of the preceding claims, further comprising testing the subject for a visual field response. 20. The method of any one of the preceding claims, wherein the subject is a visual field responder. 21. The method of any one of the preceding claims, wherein the subject is suffering from achromatopsia (ACHM). 22. The method of any one of the preceding claims, wherein the subject has at least one mutation in an achromatopsia (ACHM)-associated gene selected from the group consisting of ATF6, CNGA3, CNGB3, GNAT2, PDE6C, and PDE6H. 23 The method of any one of the preceding claims, which results in the amelioration of one or more symptoms of achromatopsia (ACHM). 24. The method of any one of the preceding claims, which results in a decrease in central hyperautofluorescence, optionally, as compared to a baseline measurement. 25. The method of any one of the preceding claims, wherein the one or more symptoms of a d achromatopsia (ACHM) is selected from the group consisting of a reduced visual acuity, a pendular nystagmus, an increased sensitivity to light (photophobia), a small central scotoma, and/or a reduced or complete loss of color discrimination. 26. The method of any one of the preceding claims, which results in an improvement in visual sensitivity measured by static perimetry, optionally, as compared to a baseline measurement. 27. The method of any one of the preceding claims, which results in an improvement in light discomfort thresholds measured using an ocular photosensitivity analyzer (OPA), optionally, as compared to a baseline measurement. 28. The method of any one of the preceding claims, which results in an improvement in electrical signaling in the retina as measured by multi-focal electroretinography (mfERG), optionally, as compared to a baseline measurement. 29. The method of any one of claims 26-28, wherein the improvement in visual sensitivity, light discomfort thresholds, and/or electrical signaling in the retina is maintained over a period of time comprising at least about 1 month or more. 30. The method of any one of claims 26-29, wherein the improvement in visual sensitivity, light discomfort thresholds, and/or electrical signaling in the retina is maintained for the lifetime of the subject. 31. The method of any one of the preceding claims, wherein the therapy suitable for treating achromatopsia (ACHM) comprises a gene therapy. 32. The method of claim 31, wherein the gene therapy comprises a nucleic acid sequence encoding an achromatopsia (ACHM)-associated gene. 33. The method of claim 32, wherein the achromatopsia (ACHM)-associated gene is selected from the group consisting of ATF6, CNGA3, CNGB3, GNAT2, PDE6C, and PDE6H. 34. The method of claim 32 or 33, wherein the nucleic acid sequence is codon optimized for mammalian expression. 35. The method of any one of claims 32-34, wherein: (i) the nucleic acid sequence comprises SEQ ID NO: [1], or a sequence at least 85% identical to SEQ ID NO: [1]; or (i) the nucleic acid sequence comprises SEQ ID NO: [150], or a sequence at least 85% identical to SEQ ID NO: [150]. 36. The method of any one of claims 32-35, wherein the nucleic acid sequence is a cDNA sequence. 37. The method of any one of claims 32-36, wherein the nucleic acid sequence is operably linked to a promoter. 38. The method of claim 37, wherein the promoter comprises a PR1.7 promoter (SEQ ID NO: 2). 39. The method of any one of claims 32-38, wherein the nucleic acid sequence further comprises an operably linked minimal regulatory element. 40. The method of claim 39, wherein the minimal regulatory element comprises a polyadenylation site, splicing signal sequences, and/or AAV inverted terminal repeats. 41. The method of claim 40, wherein the nucleic acid sequence further comprises an operably linked polyadenylation signal (pA), optionally, a SV(40) polyA. 42. The method of any one of claims 31-41, wherein the gene therapy comprises a vector. 43. The vector of claim 42, wherein the vector is an adeno-associated viral (AAV) vector. 44. The vector of claim 43, wherein the serotype of the capsid sequence and the serotype of the ITRs of said AAV vector are independently selected from the group consisting of AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10, AAV11, and AAV12. 45. The vector of claim 44, wherein the capsid sequence is a mutant capsid sequence. 46. The method of claim 42-45, wherein the vector comprises a recombinant adeno- associated (rAAV) expression vector. 47. The method of any one of claims 42-46, wherein the vector comprises a transgene expression cassette comprising a promoter; an achromatopsia (ACHM)-associated gene nucleic acid; and minimal regulatory elements. 48. The method of claim 47, wherein the minimal regulatory elements comprise a polyadenylation site, splicing signal sequences, and/or AAV inverted terminal repeats. 49. The method of claim 48, wherein the minimal regulatory elements comprise a poly adenylation (SV40 poly A) signal and flanking AAV inverted terminal repeats (ITR). 50. The method of any one of claims 44-49, wherein the serotype of the capsid sequence and the serotype of the ITRs of said AAV vector are independently selected from the group consisting of AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10, AAV11, and AAV12. 51. The method of claim 50, wherein the serotype of the capsid sequence is AAV2. 52. The method of claim 50, wherein the capsid sequence is a mutant capsid sequence. 53. The method of any one of claims 42-53, wherein the vector is administered to the subject subretinally. |
According to some embodiments, the CNGB3 nucleic acid comprises the nucleic acid sequence of SEQ ID NO: 1. According to some embodiments, the CNGB3 nucleic acid consists of the nucleic acid sequence of SEQ ID NO: 1. According to some embodiments, the nucleic acid is at least 85% identical to SEQ ID NO: 1. According to some embodiments, the nucleic acid is at least 90% identical to SEQ ID NO: 1 According to some embodiments, the nucleic acid is at least 95% identical to SEQ ID NO: 1. According to some embodiments, the nucleic acid is at least 99% identical to SEQ ID NO: 1. According to some embodiments, the CNGB3 nucleic acid is codon optimized for mammalian expression. According to some embodiments, the CNGA3 nucleic acid comprises the sequence of hCNGA3co (SEQ ID NO: 150), or a portion thereof. SEQ ID NO: 150 According to some embodiments, the CNGA3 nucleic acid comprises the nucleic acid sequence of SEQ ID NO: 150. According to some embodiments, the CNGA3 nucleic acid consists of the nucleic acid sequence of SEQ ID NO: 150. According to some embodiments, the nucleic acid is at least 85% identical to SEQ ID NO: 150. According to some embodiments, the nucleic acid is at least 90% identical to SEQ ID NO: 150 According to some embodiments, the nucleic acid is at least 95% identical to SEQ ID NO: 150. According to some embodiments, the nucleic acid is at least 99% identical to SEQ ID NO: 150. According to some embodiments, the CNGA3 nucleic acid is codon optimized for mammalian expression. Making the nucleic acids of the invention A nucleic acid molecule (including, for example, an achromatopsia (ACHM)-associated nucleic acid, such as a CNGB3 and/or CNGA3 nucleic acids) of the present invention can be isolated using standard molecular biology techniques. Using all or a portion of a nucleic acid sequence of interest as a hybridization probe, nucleic acid molecules can be isolated using standard hybridization and cloning techniques (e.g., as described in Sambrook, J., Fritsh, E. F., and Maniatis, T. Molecular Cloning. A Laboratory Manual.2nd, ed., Cold Spring Harbor Laboratory, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1989). A nucleic acid molecule for use in the methods of the invention can also be isolated by the polymerase chain reaction (PCR) using synthetic oligonucleotide primers designed based upon the sequence of a nucleic acid molecule of interest. A nucleic acid molecule used in the methods of the invention can be amplified using cDNA, mRNA or, alternatively, genomic DNA as a template and appropriate oligonucleotide primers according to standard PCR amplification techniques. Furthermore, oligonucleotides corresponding to nucleotide sequences of interest can also be chemically synthesized using standard techniques. Numerous methods of chemically synthesizing polydeoxynucleotides are known, including solid-phase synthesis which has been automated in commercially available DNA synthesizers (See e.g., Itakura et al. U.S. Patent No. 4,598,049; Caruthers et al. U.S. Patent No.4,458,066; and Itakura U.S. Patent Nos.4,401,796 and 4,373,071, incorporated by reference herein). Automated methods for designing synthetic oligonucleotides are available. See e.g., Hoover, D.M. & Lubowski, 2002. J. Nucleic Acids Research, 30(10): e43. Many embodiments of the invention involve an achromatopsia (ACHM)-associated nucleic acid. Some aspects and embodiments of the invention involve other nucleic acids, such as isolated promoters or regulatory elements. A nucleic acid may be, for example, a cDNA or a chemically synthesized nucleic acid. A cDNA can be obtained, for example, by amplification using the polymerase chain reaction (PCR) or by screening an appropriate cDNA library. Alternatively, a nucleic acid may be chemically synthesized. III. PROMOTERS, EXPRESSION CASSETTES AND VECTORS The promoters, achromatopsia (ACHM)-associated nucleic acids (e.g., CNGB3 and/or CNGA3 nucleic acids), regulatory elements, and expression cassettes, and vectors of the disclosure may be produced using methods known in the art. The methods described below are provided as non-limiting examples of such methods. Furthermore, the promoters, achromatopsia (ACHM)-associated nucleic acids (e.g., CNGB3 and/or CNGA3 nucleic acids), regulatory elements, and expression cassettes, and vectors of the disclosure may be used according to any of the methods describes herein, e.g., for treating or selecting a subject for treatment of a retinal disease or disorder, including, without limitation, achromatopsia (ACHM), for example, based on an analysis of the subject’s retinal structure and/or function. Promoters Exemplary promoters include, but are not limited to, the cytomegalovirus (CMV) immediate early promoter, the RSV LTR, the MoMLV LTR, the phosphoglycerate kinase-1 (PGK) promoter, a simian virus 40 (SV40) promoter and a CK6 promoter, a transthyretin promoter (TTR), a TK promoter, a tetracycline responsive promoter (TRE), an HBV promoter, an hAAT promoter, a LSP promoter, chimeric liver-specific promoters (LSPs), the E2F promoter, the telomerase (hTERT) promoter; the chicken beta-actin promoter, the small version of the hybrid CMV-chicken beta-actin promoter (smCBA) (Pang et al., Invest Ophthalmol Vis Sci.2008 Oct; 49(10):4278-83); the a cytomegalovirus enhancer linked to a chicken beta-actin (CBA) promoter; the cytomegalovirus enhancer/chicken beta-actin/Rabbit beta-globin promoter (CAG promoter; Niwa et al., Gene, 1991, 108(2):193-9) and the elongation factor 1-alpha promoter (EF1-alpha) promoter (Kim et al., Gene, 1990, 91(2):217-23 and Guo et al., Gene Ther., 1996, 3(9):802-10). In some embodiments, the promoter comprises the chicken beta-actin promoter. According to some embodiments, the promoter comprises the small version of the hybrid CMV-chicken beta-actin promoter (smCBA) The promoter can be a constitutive inducible or repressible promoter. In some embodiments, the promoter is capable of expressing the heterologous nucleic acid in a cell of the eye. In some embodiments, the promoter is capable of expressing the heterologous nucleic acid in photoreceptor cells or RPE. In some embodiments, the promoter is capable of expressing the heterologous nucleic acid in a multitude of retinal cells. In other embodiments, the promoter may comprise segments of a achromatopsia (ACHM)-associated gene, for example, a human achromatopsia (ACHM)- associated gene. In other embodiments, the achromatopsia (ACHM)-associated gene is a achromatopsia (ACHM)-associated gene from a non-human animal. In other embodiments, the promoter may comprise segments of a CNGB3 gene, for example, a human CNGB3 (hCNGB3) gene. In other embodiments, the CNGB3 gene is a CNGB3 gene from a non-human animal. In other embodiments, the promoter may comprise segments of a CNGA3 gene, for example, a human CNGA3 (hCNGA3) gene. In other embodiments, the CNGA3 gene is a CNGA3 gene from a non-human animal. In some embodiments, the promoter is capable of promoting expression of a transgene in S-cone, M-cone, and L-cone cells. A “transgene” refers to a segment of DNA containing a gene sequence that has been isolated from one organism and is introduced into a different organism. For example, to treat an individual who has achromatopsia caused by a mutation of an achromatopsia (ACHM)-associated gene, a wild-type (i.e., non-mutated, or functional variant) achromatopsia (ACHM)-associated gene may be administered using an appropriate vector. The wild-type gene is referred to as a “transgene.” In preferred embodiments, the transgene is a wild-type version of a gene that encodes a protein that is normally expressed in cone cells of the retina. In one such embodiment, the transgene is derived from a human gene. In a first specific embodiment, the promoter is capable of promoting expression of an achromatopsia (ACHM)- associated nucleic acid in S-cone, M-cone, and/or L-cone cells. For example, to treat an individual who has achromatopsia caused by a mutation of the human CNGB3 gene, a wild-type (i.e., non-mutated, or functional variant) human CNGB3 gene may be administered using an appropriate vector. The wild-type gene is referred to as a “transgene.” In preferred embodiments, the transgene is a wild-type version of a gene that encodes a protein that is normally expressed in cone cells of the retina. In one such embodiment, the transgene is derived from a human gene. In a first specific embodiment, the promoter is capable of promoting expression of a CNGB3 nucleic acid in S-cone, M-cone, and/or L-cone cells. In these specific embodiments, the CNGB3, is preferably human CNGB3. (See, e.g., WO2014186160, incorporated by reference herein). For example, to treat an individual who has achromatopsia caused by a mutation of the human CNGA3 gene, a wild-type (i.e., non-mutated, or functional variant) human CNGA3 gene may be administered using an appropriate vector. The wild-type gene is referred to as a “transgene.” In preferred embodiments, the transgene is a wild-type version of a gene that encodes a protein that is normally expressed in cone cells of the retina. In one such embodiment, the transgene is derived from a human gene. In a first specific embodiment, the promoter is capable of promoting expression of a CNGA3 nucleic acid in S-cone, M-cone, and/or L-cone cells. In these specific embodiments, the CNGA3, is preferably human CNGA3. (See, e.g., WO2014186160, incorporated by reference herein). In another aspect, the present invention provides promoters that are shortened versions of the PR2.1 promoter (See, e.g., WO2014186160, incorporated by reference herein), which may optionally include additional enhancer sequences. Such promoters have the advantage that they fit better within the packaging capacity of AAV vectors and therefore provide advantages such as, for example, improved yields, a lower empty-to-full particle ratio, and higher infectivity of the vector. In some embodiments, these promoters are created by truncating the 5’-end of PR2.1 while leaving the 500bp core promoter and the 600bp locus control region (LCR) intact. In some such embodiments, the lengths of the truncations are selected from the group consisting of approximately 300bp, 500bp, and 1,100 bp (see, e.g., PR1.7, PR1.5, and PR1.1, respectively, as described in Example 1 of WO2014186160). In one particular embodiment, the present invention provides a PR1.7 promoter (SEQ ID NO: 2). SEQ ID NO: 2
Expression Cassettes In another aspect, the present invention provides a transgene expression cassette that includes (a) a promoter; (b) a nucleic acid comprising a CNGB3 nucleic acid as described herein; and (c) minimal regulatory elements. A promoter of the invention includes the promoters discussed supra. According to some embodiments, the promoter a PR1.7 promoter (SEQ ID NO: 2). According to some embodiments, a nucleic acid of the present invention encodes an achromatopsia (ACHM)-associated gene. According to some embodiments, a nucleic acid of the present invention encodes a CNGB3 gene. According to some embodiments, a nucleic acid of the present invention encodes a CNGA3 gene. A “CNGB3 nucleic acid” refers to a nucleic acid that comprises the CNGB3 gene or a portion thereof, or a functional variant of the CNGB3 gene or a portion thereof. Similarly, a “CNGA3 nucleic acid” refers to a nucleic acid that comprises the CNGA3 gene or a portion thereof, or a functional variant of the CNGA3 gene or a portion thereof. A functional variant of a gene includes a variant of the gene with minor variations such as, for example, silent mutations, single nucleotide polymorphisms, missense mutations, and other mutations or deletions that do not significantly alter gene function. In certain embodiments, the nucleic acid is a human nucleic acid (i.e., a nucleic acid that is derived from a human CNGB3 gene). In other embodiments, the nucleic acid is a non- human nucleic acid (i.e., a nucleic acid that is derived from a non-human CNGB3 gene). According to some embodiments, the CNGB3 nucleic acid comprises the sequence of hCNGB3co (SEQ ID NO: 1), or a portion thereof. In some embodiments, the nucleic acid consists of SEQ ID NO: 1. According to some embodiments, the nucleic acid is at least 85% identical to SEQ ID NO: 1. According to some embodiments, the nucleic acid is at least 90% identical to SEQ ID NO: 1. According to some embodiments, the nucleic acid is at least 95% identical to SEQ ID NO: 1. According to some embodiments, the nucleic acid is at least 99% identical to SEQ ID NO: 1. In certain embodiments, the nucleic acid is a human nucleic acid (i.e., a nucleic acid that is derived from a human CNGA3 gene). In other embodiments, the nucleic acid is a non- human nucleic acid (i.e., a nucleic acid that is derived from a non-human CNGA3 gene). According to some embodiments, the CNGA3 nucleic acid comprises the sequence of hCNGA3co (SEQ ID NO: 150), or a portion thereof. In some embodiments, the nucleic acid consists of SEQ ID NO: 150. According to some embodiments, the nucleic acid is at least 85% identical to SEQ ID NO: 150. According to some embodiments, the nucleic acid is at least 90% identical to SEQ ID NO: 150. According to some embodiments, the nucleic acid is at least 95% identical to SEQ ID NO: 150. According to some embodiments, the nucleic acid is at least 99% identical to SEQ ID NO: 150. According to some embodiments, the recombinant nucleic acid is flanked by at least two ITRs. According to some embodiments, the ITRs comprises the sequences of SEQ ID NO: 3 and SEQ ID NO: 4. SEQ ID NO: 3 According to some embodiments, the construct comprises a CNGB3 nucleic acid comprising the sequence of hCNGB3co (SEQ ID NO: 1), or a portion thereof, and inverted terminal repeats (TR-PR1.7-hCNGB3co-TR). According to some embodiments, TR-PR1.7-hCNGB3co-TR comprises the nucleic acid sequence of SEQ ID NO: 100. SEQ ID NO: 100
According to some embodiments, TR-PR1.7-hCNGB3co-TR consists of the nucleic acid sequence of SEQ ID NO: 100. According to some embodiments, the nucleic acid is at least 85% identical to SEQ ID NO: 100. According to some embodiments, the nucleic acid is at least 90% identical to SEQ ID NO: 100. According to some embodiments, the nucleic acid is at least 95% identical to SEQ ID NO: 100. According to some embodiments, the nucleic acid is at least 99% identical to SEQ ID NO: 100. According to some embodiments, the construct comprises a CNGA3 nucleic acid comprising the sequence of hCNGA3co (SEQ ID NO: 150), or a portion thereof, and inverted terminal repeats (TR-PR1.7-hCNGA3co-TR). According to some embodiments, TR-PR1.7-hCNGA3co-TR comprises the nucleic acid sequence of SEQ ID NO: 200. SEQ ID NO: 200
According to some embodiments, TR-PR1.7-hCNGA3co-TR consists of the nucleic acid sequence of SEQ ID NO: 200. According to some embodiments, the nucleic acid is at least 85% identical to SEQ ID NO: 200. According to some embodiments, the nucleic acid is at least 90% identical to SEQ ID NO: 200. According to some embodiments, the nucleic acid is at least 95% identical to SEQ ID NO: 200. According to some embodiments, the nucleic acid is at least 99% identical to SEQ ID NO: 200. “Minimal regulatory elements” are regulatory elements that are necessary for effective expression of a gene in a target cell Such regulatory elements could include for example promoter or enhancer sequences, a polylinker sequence facilitating the insertion of a DNA fragment within a plasmid vector, and sequences responsible for intron splicing and polyadenylation of mRNA transcripts. In a recent example of a gene therapy treatment for achromatopsia, the expression cassette included the minimal regulatory elements of a polyadenylation site, splicing signal sequences, and AAV inverted terminal repeats. See, e.g., Komaromy et al.. The expression cassettes of the invention may also optionally include additional regulatory elements that are not necessary for effective incorporation of a gene into a target cell. According to some embodiments, the construct comprises a SV(40) polyA. Vectors The present invention also provides vectors that include any one of the expression cassettes discussed in the preceding section. In some embodiments, the vector is an oligonucleotide that comprises the sequences of the expression cassette. In specific embodiments, delivery of the oligonucleotide may be accomplished by in vivo electroporation (see, e.g., Chalberg, TW, et al. Investigative Ophthalmology &Visual Science, 46, 2140–2146 (2005) (hereinafter Chalberg et al., 2005)) or electron avalanche transfection (see, e.g., Chalberg, TW, et al. Investigative Ophthalmology &Visual Science, 47, 4083–4090 (2006) (hereinafter Chalberg et al., 2006)). In further embodiments, the vector is a DNA-compacting peptide (see, e.g., Farjo, R, et al. PLoS ONE, 1, e38 (2006) (hereinafter Farjo et al., 2006), where CK30, a peptide containing a cysteine residue coupled to polyethylene glycol followed by 30 lysines, was used for gene transfer to photoreceptors), a peptide with cell penetrating properties (see Johnson, LN, et al., Cell-penetrating peptide for enhanced delivery of nucleic acids and drugs to ocular tissues including retina and cornea. Molecular Therapy, 16(1), 107–114 (2007) (hereinafter Johnson et al., 2007), Barnett, EM, et al. Investigative Ophthalmology & Visual Science, 47, 2589–2595 (2006) (hereinafter Barnett et al., 2006), Cashman, SM, et al. Molecular Therapy, 8, 130–142 (2003) (hereinafter Cashman et al., 2003), Schorderet, DF, et al. Clinical and Experimental Ophthalmology, 33, 628–635 (2005) (hereinafter Schorderet et al., 2005), Kretz, A, et al.. Molecular Therapy, 7, 659–669 (2003) (hereinafter Kretz et al.2003) for examples of peptide delivery to ocular cells), or a DNA-encapsulating lipoplex, polyplex, liposome, or immunoliposome (see e.g., Zhang, Y, et al. Molecular Vision, 9, 465–472 (2003) (hereinafter Zhang et al.2003), Zhu, C, et al. Investigative Ophthalmology & Visual Science, 43, 3075–3080 (2002) (hereinafter Zhu et al.2002), Zhu, C., et al. Journal of Gene Medicine, 6, 906–912. (2004) (hereinafter Zhu et al.2004)). In preferred embodiments, the vector is a viral vector, such as a vector derived from an adeno-associated virus, an adenovirus, a retrovirus, a lentivirus, a vaccinia/poxvirus, or a herpesvirus (e.g., herpes simplex virus (HSV)). See e.g., Howarth, JL et al., Using viral vectors as gene transfer tools. Cell Biol Toxicol 26:1-10 (2010). In the most preferred embodiments, the vector is an adeno-associated viral (AAV) vector. Multiple serotypes of adeno-associated virus (AAV), including 12 human serotypes (AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10, AAV11, and AAV12) and more than 100 serotypes from nonhuman primates have now been identified. Howarth JL et al., 2010. In embodiments of the present invention wherein the vector is an AAV vector, the serotype of the inverted terminal repeats (ITRs) of the AAV vector may be selected from any known human or nonhuman AAV serotype. In preferred embodiments, the serotype of the AAV ITRs of the AAV vector is selected from the group consisting of AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10, AAV11, and AAV12. Moreover, in embodiments of the present invention wherein the vector is an AAV vector, the serotype of the capsid sequence of the AAV vector may be selected from any known human or animal AAV serotype. In some embodiments, the serotype of the capsid sequence of the AAV vector is selected from the group consisting of AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10, AAV11, and AAV12. In preferred embodiments, the serotype of the capsid sequence is AAV2. In some embodiments wherein the vector is an AAV vector, a pseudotyping approach is employed, wherein the genome of one ITR serotype is packaged into a different serotype capsid. See e.g., Zolutuhkin S. et al. Methods 28(2): 158-67 (2002). In preferred embodiments, the serotype of the AAV ITRs of the AAV vector and the serotype of the capsid sequence of the AAV vector are independently selected from the group consisting of AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10, AAV11, and AAV12. In some embodiments of the present invention wherein the vector is a rAAV vector, a mutant capsid sequence is employed. Mutant capsid sequences, as well as other techniques such as rational mutagenesis, engineering of targeting peptides, generation of chimeric particles, library and directed evolution approaches, and immune evasion modifications, may be employed in the present invention to optimize AAV vectors, for purposes such as achieving immune evasion and enhanced therapeutic output. See e.g., Mitchell A.M. et al. AAV’s anatomy: Roadmap for optimizing vectors for translational success. Curr Gene Ther.10(5): 319-340. AAV vectors can mediate long term gene expression in the retina and elicit minimal immune responses making these vectors an attractive choice for gene delivery to the eye. IV. METHODS OF PRODUCING VIRAL VECTORS The present disclosure also provides methods of making a recombinant adeno-associated viral (rAAV) vectors comprising inserting into an adeno-associated viral vector any one of the nucleic acids described herein. According to some embodiments, the rAAV vector further comprises one or more AAV inverted terminal repeats (ITRs). According to the methods of making an rAAV vector that are provided by the disclosure, the serotype of the capsid sequence and the serotype of the ITRs of said AAV vector are independently selected from the group consisting of AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10, AAV11, and AAV12. Thus, the disclosure encompasses vectors that use a pseudotyping approach, wherein the vector genome of one ITR serotype is packaged into a different serotype capsid. See e.g., Daya S. and Berns, K.I., Gene therapy using adeno-associated virus vectors. Clinical Microbiology Reviews, 21(4): 583-593 (2008) (hereinafter Daya et al.). Furthermore, in some embodiments, the capsid sequence is a mutant capsid sequence. AAV Vectors AAV vectors are derived from adeno-associated virus, which has its name because it was originally described as a contaminant of adenovirus preparations. AAV vectors offer numerous well-known advantages over other types of vectors: wildtype strains infect humans and nonhuman primates without evidence of disease or adverse effects; the AAV capsid displays very low immunogenicity combined with high chemical and physical stability which permits rigorous methods of virus purification and concentration; AAV vector transduction leads to sustained transgene expression in post-mitotic, nondividing cells and provides long-term gain of function; and the variety of AAV subtypes and variants offers the possibility to target selected tissues and cell types. Heilbronn R & Weger S, Viral Vectors for Gene Transfer: Current Status of Gene Therapeutics, in M. Schäfer-Korting (ed.), Drug Delivery, Handbook of Experimental Pharmacology, 197: 143-170 (2010) (hereinafter Heilbronn). A major limitation of AAV vectors is that the AAV offers only a limited transgene capacity (<4.9 kb) for a conventional vector containing single-stranded DNA. AAV is a nonenveloped, small, single-stranded DNA-containing virus encapsidated by an icosahedral, 20 nm diameter capsid. The human serotype AAV2 was used in a majority of early studies of AAV. Heilbronn (2010). It contains a 4.7 kb linear, single-stranded DNA genome with two open reading frames rep and cap (“rep” for replication and “cap” for capsid). Rep codes for four overlapping nonstructural proteins: Rep78, Rep68, Rep52, and Rep40. Rep78 and Rep69 are required for most steps of the AAV life cycle, including the initiation of AAV DNA replication at the hairpin-structured inverted terminal repeats (ITRs), which is an essential step for AAV vector production. The cap gene codes for three capsid proteins, VP1, VP2, and VP3. Rep and cap are flanked by the 145 bp ITRs. The ITRs contain the origins of DNA replication and the packaging signals, and they serve to mediate chromosomal integration. The ITRs are generally the only AAV elements maintained in AAV vector construction. To achieve replication, AAVs must be coinfected into the target cell with a helper virus. Grieger JC & Samulski RJ, Adeno-associated virus as a gene therapy vector: Vector development, production, and clinical applications. Adv Biochem Engin/Biotechnol 99:119-145 (2005). Typically, helper viruses are either adenovirus (Ad) or herpes simplex virus (HSV). In the absence of a helper virus, AAV can establish a latent infection by integrating into a site on human chromosome 19. Ad or HSV infection of cells latently infected with AAV will rescue the integrated genome and begin a productive infection. The four Ad proteins required for helper function are E1A, E1B, E4, and E2A. In addition, synthesis of Ad virus-associated (VA) RNAs is required. Herpesviruses can also serve as helper viruses for productive AAV replication. Genes encoding the helicase-primase complex (UL5, UL8, and UL52) and the DNA-binding protein (UL29) have been found sufficient to mediate the HSV helper effect. In some embodiments of the present invention that employ rAAV vectors, the helper virus is an adenovirus. In other embodiments that employ rAAV vectors, the helper virus is HSV. Making recombinant AAV (rAAV) vectors The production, purification, and characterization of the rAAV vectors of the present invention may be carried out using any of the many methods known in the art. For reviews of laboratory-scale production methods, see, e.g., Clark RK, Kidney Int.61s:9-15 (2002); Choi VW et al., Current Protocols in Molecular Biology 16.25.1-16.25.24 (2007) (hereinafter Choi et al.); Grieger JC & Samulski RJ, Adv Biochem Engin/Biotechnol 99:119-145 (2005) (hereinafter Grieger & Samulski); Heilbronn R & Weger S, in M. Schäfer-Korting (ed.), Drug Delivery, Handbook of Experimental Pharmacology, 197: 143-170 (2010) (hereinafter Heilbronn); Howarth JL et al., Cell Biol Toxicol 26:1-10 (2010) (hereinafter Howarth). The production methods described below are intended as non-limiting examples. AAV vector production may be accomplished by cotransfection of packaging plasmids. Heilbronn. The cell line supplies the deleted AAV genes rep and cap and the required helpervirus functions. The adenovirus helper genes, VA-RNA, E2A and E4 are transfected together with the AAV rep and cap genes, either on two separate plasmids or on a single helper construct. A recombinant AAV vector plasmid wherein the AAV capsid genes are replaced with a transgene expression cassette (comprising the gene of interest, e.g., an achromatopsia (ACHM)-associated gene, such as a CNGB3 nucleic acid and/or a CNGA3 nucleic acid as described herein; a promoter; and minimal regulatory elements) bracketed by ITRs, is also transfected. These packaging plasmids can be transfected into adherent or suspension cell lines. According to some embodiments, these packaging plasmids are typically transfected into HEK 293 or HEK293T cells, a human cell line that constitutively expresses the remaining required Ad helper genes, E1A and E1B. This leads to amplification and packaging of the AAV vector carrying the gene of interest. Multiple serotypes of AAV, including 12 human serotypes and more than 100 serotypes from nonhuman primates have now been identified. Howarth et al. The AAV vectors of the present invention may comprise capsid sequences derived from AAVs of any known serotype. As used herein, a “known serotype” encompasses capsid mutants that can be produced using methods known in the art. Such methods include, for example, genetic manipulation of the viral capsid sequence, domain swapping of exposed surfaces of the capsid regions of different serotypes, and generation of AAV chimeras using techniques such as marker rescue. See Bowles et al. Journal of Virology, 77(1): 423-432 (2003), as well as references cited therein. Moreover, the AAV vectors of the present invention may comprise ITRs derived from AAVs of any known serotype. Preferentially, the ITRs are derived from one of the human serotypes AAV1-AAV12. In some embodiments of the present invention, a pseudotyping approach is employed, wherein the genome of one ITR serotype is packaged into a different serotype capsid. Preferentially, the capsid sequences employed in the present invention are derived from one of the human serotypes AAV1-AAV12. Recombinant AAV vectors containing an AAV5 serotype capsid sequence have been demonstrated to target retinal cells in vivo. See, for example, Komaromy et al. Therefore, in preferred embodiments of the present invention, the serotype of the capsid sequence of the AAV vector is AAV2. In other embodiments, the serotype of the capsid sequence of the AAV vector is AAV1, AAV2, AAV3, AAV4, AAV6, AAV7, AAV8, AAV9, AAV10, AAV11, or AAV12. Even when the serotype of the capsid sequence does not naturally target retinal cells, other methods of specific tissue targeting may be employed. See Howarth et al. One possible protocol for the production, purification, and characterization of recombinant AAV (rAAV) vectors is provided in Choi et al. Generally, the following steps are involved: design a transgene expression cassette, design a capsid sequence for targeting a specific receptor, generate adenovirus-free rAAV vectors, purify and titer. These steps are summarized below and described in detail in Choi et al. The transgene expression cassette may be a single-stranded AAV (ssAAV) vector or a “dimeric” or self-complementary AAV (scAAV) vector that is packaged as a pseudo-double- stranded transgene. Choi et al.; Heilbronn; Howarth. Using a traditional ssAAV vector generally results in a slow onset of gene expression (from days to weeks until a plateau of transgene expression is reached) due to the required conversion of single-stranded AAV DNA into double-stranded DNA. In contrast, scAAV vectors show an onset of gene expression within hours that plateaus within days after transduction of quiescent cells. Heilbronn. However, the packaging capacity of scAAV vectors is approximately half that of traditional ssAAV vectors. Choi et al. Alternatively, the transgene expression cassette may be split between two AAV vectors, which allows delivery of a longer construct. See e.g., Dyka et al. Hum Gene Ther.2019 Sep 30. A ssAAV vector can be constructed by digesting an appropriate plasmid (such as, for example, a plasmid containing the achromatopsia (ACHM)-associated gene, such as the CNGB3 nucleic gene and/or the CNGA3 gene) with restriction endonucleases to remove the rep and cap fragments, and gel purifying the plasmid backbone containing the AAVwt-ITRs. Choi et al. Subsequently, the desired transgene expression cassette can be inserted between the appropriate restriction sites to construct the single-stranded rAAV vector plasmid. A scAAV vector can be constructed as described in Choi et al. Then, a large-scale plasmid preparation (at least 1 mg) of the rAAV vector and the suitable AAV helper plasmid and pXX6 Ad helper plasmid can be purified (Choi et al.). A suitable AAV helper plasmid may be selected from the pXR series, pXR1-pXR5, which respectively permit cross-packaging of AAV2 ITR genomes into capsids of AAV serotypes 1 to 12 and variants thereof. The appropriate capsid may be chosen based on the efficiency of the capsid’s targeting of the cells of interest. For example, in a preferred embodiment of the present invention, the serotype of the capsid sequence of the rAAV vector is AAV2, because this type of capsid is known to effectively target retinal cells. Known methods of varying genome (i.e., transgene expression cassette) length and AAV capsids may be employed to improve expression and/or gene transfer to specific cell types (e.g., retinal cone cells). See, e.g., Yang GS, Journal of Virology, 76(15): 7651-7660. Next, HEK293 or HEK293T cells are transfected with pXX6 helper plasmid, rAAV vector plasmid, and AAV helper plasmid. Choi et al. Subsequently the fractionated cell lysates are subjected to a multistep process of rAAV purification, followed by either CsCl gradient purification, or heparin sepharose column purification. The production and quantitation of rAAV virions may be determined using a dot-blot assay. In vitro transduction of rAAV in cell culture can be used to verify the infectivity of the virus and functionality of the expression cassette. In addition to the methods described in Choi et al., various other transfection & purification methods for production of AAV may be used in the context of the present invention. For example, transient transfection methods are available, including methods that rely on a calcium phosphate precipitation or PEI protocol. The various purification methods include iodixanol gradient purification, affinity and/or ion-exchanger column chromatography. In addition to the laboratory-scale methods for producing rAAV vectors, the present invention may utilize techniques known in the art for bioreactor-scale manufacturing of AAV vectors, including, for example, Heilbronn; Clement, N. et al. Human Gene Therapy, 20: 796- 606. According to some embodiments, the method for producing rAAV vectors is carried out as described in Chulay et al. (Hum Gene Ther.2011 Feb;22(2):155-65), incorporated by reference in its entirety herewith. V. METHODS OF SELECTION AND TREATMENT The present disclosure provides methods that can be used in the treatment of retinal diseases or disorders, including, without limitation, achromatopsia (ACHM). In particular, the present invention provides methods of treatment or methods of selecting a subject for treatment of a retinal disease or disorder, including, without limitation, achromatopsia (ACHM), for example, based on an analysis of the subject’s retinal structure and/or function. Additionally, the present invention provides methods for predicting or determining a subject’s likely response to a therapy for treating achromatopsia (ACHM), and methods for determining a subject’s suitability to a treatment regime or intervention for achromatopsia (ACHM), for example, based on an analysis of the subject’s retinal structure and/or function. In certain embodiments, an analysis of the subject’s retinal structure and/or function may comprise an analysis by central fundus autofluorescence and/or optical coherence tomography morphology. Central Fundus Autofluorescence as a Predictor for Achromatopsia Therapy Fundus autofluorescence (FAF) is a non-invasive retinal imaging modality used, for example, to provide a density map of lipofuscin, the predominant ocular fluorophore, in the retinal pigment epithelium. Multiple commercially available imaging systems may be used to obtain FAF images, including the fundus camera, the confocal scanning laser ophthalmoscope, and the ultra-widefield imaging device. With respect to the instant invention, it is understood that, in certain embodiments, identifying a subject or selecting a subject based on an analysis of the subject’s retinal structure and/or function, can include any of a number of acts including, but not limited to, performing a test and observing a result that is indicative of a subject having a specific pattern of fundus autofluorescence; reviewing a test result of a subject and identifying the subject as having a specific pattern of fundus autofluorescence; reviewing documentation on a subject stating that the subject has a specific pattern of fundus autofluorescence and identifying the subject as the one discussed in the documentation by confirming the identity of the subject e.g., by an identification card, hospital bracelet, asking the subject for his/her name and/ or other personal information to confirm the subjects identity. In certain embodiments, identifying a subject or selecting a subject may comprise selecting the subject if a predetermined pattern of fundus autofluorescence (FAF) is present in an eye of the subject at baseline. In certain embodiments, identifying a subject or selecting a subject may comprise classifying the pattern of fundus autofluorescence (FAF) in the eye of the subject as comprising central hypoautofluorescence (grade 0), normal autofluorescence (grade 1), or mild or strong hyperautofluorescence (grade 2). In certain embodiments, (a) a pattern of FAF comprising central hypoautofluorescence (grade 0) identifies a subject that is less likely to be a visual field responder; (b) a pattern of FAF comprising normal autofluorescence (grade 1) identifies a subject that is less likely to be a visual field responder; and/or (c) a pattern of FAF comprising mild or strong hyperautofluorescence (grade 2) identifies a subject that is more likely to be a visual field responder. In certain embodiments, the predetermined pattern of fundus autofluorescence (FAF) may be mild or strong hyperautofluorescence (grade 2). In certain embodiments, the predetermined pattern of fundus autofluorescence (FAF) in the eye of the subject is obtained prior to or at the time of administration of the therapy suitable for treating achromatopsia (ACHM). In certain embodiments, identifying a subject or selecting a subject may comprise monitoring the pattern of fundus autofluorescence (FAF) in the eye of the subject for a period of time after administration of the therapy suitable for treating achromatopsia (ACHM). Optical Coherence Tomography Morphology as a Predictor for Achromatopsia Therapy With respect to the instant invention, it is understood that, in certain embodiments, identifying a subject or selecting a subject based on an analysis of the subject’s retinal structure and/or function, can include any of a number of acts including, but not limited to, performing a test and observing a result that is indicative of a subject having a specific optical coherence tomography (OCT) central outer retina morphology; reviewing a test result of a subject and identifying the subject as having a specific optical coherence tomography (OCT) central outer retina morphology; reviewing documentation on a subject stating that the subject has a specific optical coherence tomography (OCT) central outer retina morphology and identifying the subject as the one discussed in the documentation by confirming the identity of the subject e.g., by an identification card, hospital bracelet, asking the subject for his/her name and/ or other personal information to confirm the subjects identity. In certain embodiments, identifying a subject or selecting a subject may comprise selecting the subject if a predetermined optical coherence tomography (OCT) central outer retina morphology is present in an eye of the subject at baseline. In certain embodiments, identifying a subject or selecting a subject may comprise classifying the optical coherence tomography (OCT) central outer retina morphology in the eye of the subject as comprising central absence of ellipsoid zone (EZ) line disturbance (grade 0), the presence of EZ line disturbance (grade 1), or the presence of empty optical space (grade 2). In certain embodiments, (a) an OCT central outer retina morphology comprising the central absence of ellipsoid zone (EZ) line disturbance (grade 0) identifies a subject that is more likely to be a visual field responder; (b) an OCT central outer retina morphology comprising the presence of EZ line disturbance (grade 1) identifies a subject that is more likely to be a visual field responder; and/or (c) an OCT central outer retina morphology comprising the presence of empty optical space (grade 2) identifies a subject that is less likely to be a visual field responder. In certain embodiments, the predetermined optical coherence tomography (OCT) central outer retina morphology is central absence of ellipsoid zone (EZ) line disturbance (grade 0) or presence of EZ line disturbance (grade 1). Accordingly, in one aspect, the instant invention provides a method of treating a subject, comprising: (a) selecting the subject if a predetermined pattern of fundus autofluorescence (FAF) is present in an eye of the subject at baseline; and (b) administering to the subject an effective amount of a therapy suitable for treating achromatopsia (ACHM). In another aspect, the instant invention provides a method of selecting and treating a subject predisposed to achromatopsia (ACHM), comprising: (a) selecting the subject if a predetermined pattern of fundus autofluorescence (FAF) is present in an eye of the subject at baseline; and (b) administering to the subject an effective amount of a therapy suitable for treating achromatopsia (ACHM). In another aspect, the instant invention provides a method of selecting and treating a subject having achromatopsia (ACHM) that is likely to be a visual field responder, comprising: (a) selecting the subject if a predetermined pattern of fundus autofluorescence (FAF) is present in an eye of the subject at baseline; and (b) administering to the subject an effective amount of a therapy suitable for treating achromatopsia (ACHM). In another aspect, the instant invention provides a method of reducing, inhibiting and/or preventing one or more symptoms of achromatopsia (ACHM) in a subject, comprising: (a) selecting the subject if a predetermined pattern of fundus autofluorescence (FAF) is present in an eye of the subject at baseline; and (b) administering to the subject an effective amount of a therapy suitable for treating achromatopsia (ACHM). In certain embodiments, the methods described herein may further comprise classifying the pattern of fundus autofluorescence (FAF) in the eye of the subject as comprising central hypoautofluorescence (grade 0), normal autofluorescence (grade 1), or mild or strong hyperautofluorescence (grade 2). In certain embodiments, a pattern of FAF comprising central hypoautofluorescence (grade 0) identifies a subject that is less likely to be a visual field responder. In certain embodiments, a pattern of FAF comprising normal autofluorescence (grade 1) identifies a subject that is less likely to be a visual field responder. In certain embodiments, a pattern of FAF comprising mild or strong hyperautofluorescence (grade 2) identifies a subject that is more likely to be a visual field responder In certain embodiments a subject is selected based on the predetermined pattern of fundus autofluorescence (FAF) is mild or strong hyperautofluorescence (grade 2). In certain embodiments, the predetermined pattern of fundus autofluorescence (FAF) in the eye of the subject is obtained prior to or at the time of administration of the therapy suitable for treating achromatopsia (ACHM). In certain embodiments, the methods described herein may further comprise monitoring the pattern of fundus autofluorescence (FAF) in the eye of the subject for a period of time after administration of the therapy suitable for treating achromatopsia (ACHM). In one aspect, the instant invention provides a method of treating a subject, comprising: (a) selecting the subject if a predetermined optical coherence tomography (OCT) central outer retina morphology is present in an eye of the subject at baseline; and (b) administering to the subject an effective amount of a therapy suitable for treating achromatopsia (ACHM). In one aspect, the instant invention provides a method of selecting and treating a subject predisposed to achromatopsia (ACHM), comprising: (a) selecting the subject if a predetermined optical coherence tomography (OCT) central outer retina morphology is present in an eye of the subject at baseline; and (b) administering to the subject an effective amount of a therapy suitable for treating achromatopsia (ACHM). In one aspect, the instant invention provides a method of selecting and treating a subject having achromatopsia (ACHM) that is more likely to be a visual field responder, comprising: (a) selecting the subject if a predetermined optical coherence tomography (OCT) central outer retina morphology is present in an eye of the subject at baseline; and (b) administering to the subject an effective amount of a therapy suitable for treating achromatopsia (ACHM). In one aspect, the instant invention provides a method of reducing, inhibiting and/or preventing one or more symptoms of achromatopsia (ACHM) in a subject, comprising: (a) selecting the subject if a predetermined optical coherence tomography (OCT) central outer retina morphology is present in an eye of the subject at baseline; and (b) administering to the subject an effective amount of a therapy suitable for treating achromatopsia (ACHM). In certain embodiments, the methods described herein may further comprise classifying the optical coherence tomography (OCT) central outer retina morphology in the eye of the subject as comprising central absence of ellipsoid zone (EZ) line disturbance (grade 0), the presence of EZ line disturbance (grade 1), or the presence of empty optical space (grade 2). In certain embodiments, an OCT central outer retina morphology comprising the central absence of ellipsoid zone (EZ) line disturbance (grade 0) identifies a subject that is more likely to be a visual field responder. In certain embodiments, an OCT central outer retina morphology comprising the presence of EZ line disturbance (grade 1) identifies a subject that is more likely to be a visual field responder. In certain embodiments, an OCT central outer retina morphology comprising the presence of empty optical space (grade 2) identifies a subject that is less likely to be a visual field responder. In certain embodiments, the predetermined optical coherence tomography (OCT) central outer retina morphology is central absence of ellipsoid zone (EZ) line disturbance (grade 0) or presence of EZ line disturbance (grade 1). In certain embodiments, the predetermined optical coherence tomography (OCT) central outer retina morphology in the eye of the subject is obtained prior to or at the time of administration of the therapy suitable for treating achromatopsia (ACHM). In certain embodiments, the methods described herein may further comprise monitoring the optical coherence tomography (OCT) central outer retina morphology in the eye of the subject for a period of time after administration of the therapy suitable for treating achromatopsia (ACHM). In certain embodiments, the methods described herein may further comprise testing the subject for a visual field response. In certain embodiments, the subject is a visual field responder. Achromatopsia is a color vision disorder. Autosomal recessive mutations or other types of sequence alterations in three genes are the predominant cause of congenital achromatopsia. See Pang, J.-J. et al. (2010). Achromatopsia as a Potential Candidate for Gene Therapy. In Advances in Experimental Medicine and Biology, Volume 664, Part 6, 639-646 (2010). Achromatopsia has been associated with mutations in either the alpha or beta subunits of cyclic nucleotide gated channels (CNGs), which are respectively known as CNGA3 and CNGB3. Mutations in the CNGA3 gene that were associated with achromatopsia are reported in Patel KA, et al. Transmembrane S1 mutations in CNGA3 from achromatopsia 2 patients cause loss of function and impaired cellular trafficking of the cone CNG channel. Invest. Ophthalmol. Vis. Sci.46 (7): 2282–90. (2005)., Johnson S, et al. Achromatopsia caused by novel mutations in both CNGA3 and CNGB3. J. Med. Genet.41 (2): e20. (2004)., Wissinger B, et al. CNGA3 mutations in hereditary cone photoreceptor disorders. Am. J. Hum. Genet.69 (4): 722– 37.(2001)., and Kohl S, et al. Total colourblindness is caused by mutations in the gene encoding the alpha-subunit of the cone photoreceptor cGMP-gated cation channel. Nat. Genet.19 (3): 257–9. (1998). Mutations in CNGB3 gene that were associated with achromatopsia are reported in Johnson S, et al. Achromatopsia caused by novel mutations in both CNGA3 and CNGB3. J. Med. Genet.41 (2): e20. (2004)., Peng C, et al. Achromatopsia-associated mutation in the human cone photoreceptor cyclic nucleotide-gated channel CNGB3 subunit alters the ligand sensitivity and pore properties of heteromeric channels. J. Biol. Chem.278 (36): 34533–40 (2003)., Bright SR, et al. Disease-associated mutations in CNGB3 produce gain of function alterations in cone cyclic nucleotide-gated channels. Mol. Vis.11: 1141–50 (2005)., Kohl S, et al. CNGB3 mutations account for 50% of all cases with autosomal recessive achromatopsia. Eur. J. Hum. Genet.13 (3): 302–8 (2005)., Rojas CV, et al. A frameshift insertion in the cone cyclic nucleotide gated cation channel causes complete achromatopsia in a consanguineous family from a rural isolate. Eur. J. Hum. Genet.10 (10): 638–42 (2002)., Kohl S, et al. Mutations in the CNGB3 gene encoding the beta-subunit of the cone photoreceptor cGMP-gated channel are responsible for achromatopsia (ACHM3) linked to chromosome 8q21. Hum. Mol. Genet.9 (14): 2107–16 (2000)., Sundin OH, et al.. Genetic basis of total colourblindness among the Pingelapese islanders. Nat. Genet.25 (3): 289–93 (2000). Sequence alterations in the gene for cone cell transducin, known as GNAT2, can also cause achromatopsia. See Kohl S, et al., Mutations in the cone photoreceptor G-protein alpha-subunit gene GNAT2 in patients with achromatopsia. Kokl S, et al. Mutations in the cone photoreceptor G-protein alpha-subunit gene GNAT2 in patients with achromatopsia. Am J Hum Genet 71 (2): 422-425 (2002) (hereinafter Kohl et al.). The severity of mutations in these proteins correlates with the severity of the achromatopsia phenotype. Mutations in CNGB3 account for about 50% of cases of achromatopsia. Kohl et al. Mutations in CNGA3 account for about 23% of cases, and mutations in GNAT2 account for about 2% of cases. The “CNGB3 gene” is the gene that encodes the cyclic nucleotide-gated channel beta 3 (CNGB3). The “CNGA3 gene” is the gene that encodes the cyclic nucleotide-gated channel alpha 3 (CNGA3). The CNGB3 and CNGA3 genes are expressed in cone cells of the retina. Native retinal cyclic nucleotide gated channels (CNGs) are critically involved in phototransduction. CNGs are cation channels that consist of two alpha and two beta subunits. In the dark, cones have a relatively high concentration of cyclic guanosine 3'-5' monophosphate (cGMP), which causes the CNGs to open, resulting in depolarization and continuous glutamate release. Light exposure activates a signal transduction pathway that breaks down cGMP. The reduction in cGMP concentration causes the CNGs to close, preventing the influx of positive ions, hyperpolarizing the cell, and stopping the release of glutamate. Mutations in either the CNGB3 or CNGA3 genes can cause defects in cone photoreceptor function resulting in achromatopsia. Mutations in the CNGB3 gene have been associated with other diseases in addition to achromatopsia, including progressive cone dystrophy and juvenile macular degeneration. The GNAT2 gene encodes the alpha-2 subunit of guanine nucleotide binding protein, which is also known as the cone-specific alpha transducin. Guanine nucleotide-binding proteins (G proteins) consist of alpha, beta, and gamma subunits. In photoreceptors, G proteins are critical in the amplification and transduction of visual signals. Various types of sequence alterations in GNAT2 can cause human achromatopsia: nonsense mutations, small deletion and/or insertion mutations, frameshift mutations, and large intragenic deletions. Pang et al. Currently, there is no effective treatment for achromatopsia. Animal studies suggest that it is possible to use gene therapy to treat achromatopsia and other diseases of the retina. For recessive gene defects, the goal is to deliver a wild-type copy of a defective gene to the affected retinal cell type. The ability to deliver genes to some subsets of cone cells was demonstrated, for example, in Mauck, M. C. et al., Longitudinal evaluation of expression of virally delivered transgenes in gerbil cone photoreceptors. Visual Neuroscience 25(3): 273-282 (2008). The authors showed that a recombinant AAV vector could be used to achieve long-term expression of a reporter gene encoding green fluorescent protein in specific types of gerbil cone cells. The authors further demonstrated that a human long-wavelength opsin gene could be delivered to specific gerbil cones, resulting in cone responses to long-wavelength light. Other studies demonstrated that gene therapy with recombinant AAV vectors could be used to convert dichromat monkeys into trichromats by introducing a human L-opsin gene into the squirrel monkey retina. Mancuso, K., et al. Gene therapy for red-green colour blindness in adult primates. Nature 461: 784-787 (2009). Electroretinograms verified that the introduced photopigment was functional, and the monkeys showed improved color vision in a behavioral test. There are several animal models of achromatopsia for which gene therapy experiments have demonstrated the ability to restore cone function. See Pang et al. First, the Gnat2 cpfl3 mouse has a recessive mutation in the cone-specific alpha transducin gene, resulting in poor visual acuity and little or no cone-specific ERT response. Treatment of homozygous Gnat2 cpfl3 mice with a single subretinal injection of an AAV serotype 5 vector carrying wild type mouse GNAT2 cDNA and a human red cone opsin promoter restored cone-specific ERG responses and visual acuity. Alexander et al. Restoration of cone vision in a mouse model of achromatopsia. Nat Med 13:685-687 (2007) (hereinafter Alexander et al.). Second, the cpfl5 (Cone Photoreceptor Function Loss 5) mouse has an autosomal recessive missense mutation in the CNGA3 gene with no cone-specific ERG response. Treatment of cpfl5 mice with subretinal injection of an AAV vector carrying the wild type mouse CNGA3 gene and a human blue cone promoter (HB570) resulted in restoration of cone-specific ERG responses. Pang et al. Third, there is an Alaskan Malamute dog that has a naturally occurring CNGB3 mutation causing loss of daytime vision and absence of retinal cone function. In this type of dog, subretinal injection of an AAV5 vector containing human CNGB3 cDNA and a human red cone opsin promoter restored cone-specific ERG responses. See, e.g., Komaromy et al. According to some embodiments, the disclosure further provides methods for treating a retinal or ocular disease or disorder (e.g. ACHM) comprising administering any of the vectors of the invention to a subject in need of such treatment, thereby treating the subject. In any of the methods of treatment, the vector can be any type of vector known in the art. In some embodiments, the vector is a non-viral vector, such as a naked DNA plasmid, an oligonucleotide (such as, e.g., an antisense oligonucleotide, a small molecule RNA (siRNA), a double stranded oligodeoxynucleotide, or a single stranded DNA oligonucleotide). In specific embodiments involving oligonucleotide vectors, delivery may be accomplished by in vivo electroporation (see e.g., Chalberg et al., 2005) or electron avalanche transfection (see e.g., Chalberg et al.2006). In further embodiments, the vector is a dendrimer/DNA complex that may optionally be encapsulated in a water soluble polymer, a DNA-compacting peptide (see e.g., Farjo et al.2006, where CK30, a peptide containing a cysteine residue coupled to poly ethylene glycol followed by 30 lysines, was used for gene transfer to photoreceptors), a peptide with cell penetrating properties (see Johnson et al.2007; Barnett et al., 2006; Cashman et al., 2003; Schorder et al., 2005; Kretz et al.2003 for examples of peptide delivery to ocular cells), or a DNA-encapsulating lipoplex, polyplex, liposome, or immunoliposome (see e.g., Zhang et al.2003; Zhu et al.2002; Zhu et al.2004). According to some embodiments, the vector is a viral vector, such as a vector derived from an adeno-associated virus, an adenovirus, a retrovirus, a lentivirus, a vaccinia/poxvirus, or a herpesvirus (e.g., herpes simplex virus (HSV)). See e.g., Howarth. In preferred embodiments, the vector is an adeno-associated viral (AAV) vector. According to some embodiments, the disclosure provides methods for treating a retinal or ocular disease or disorder (e.g. ACHM) comprising administering a rAAV vector described herein, wherein the rAAV vector comprises a nucleic acid sequence encoding CNGB3 and/or CNGA3. According to some embodiments, the nucleic acid sequences described herein are directly introduced into a cell, where the nucleic acid sequences are expressed to produce the encoded product, prior to administration in vivo of the resulting recombinant cell. This can be accomplished by any of numerous methods known in the art, e.g., by such methods as electroporation, lipofection, calcium phosphate mediated transfection. Pharmaceutical Compositions According to some aspects, the disclosure provides pharmaceutical compositions comprising any of the vectors described herein, optionally in a pharmaceutically acceptable excipient. As is well known in the art, pharmaceutically acceptable excipients are relatively inert substances that facilitate administration of a pharmacologically effective substance and can be supplied as liquid solutions or suspensions, as emulsions, or as solid forms suitable for dissolution or suspension in liquid prior to use. For example, an excipient can give form or consistency, or act as a diluent. Suitable excipients include but are not limited to stabilizing agents, wetting and emulsifying agents, salts for varying osmolarity, encapsulating agents, pH buffering substances, and buffers. Such excipients include any pharmaceutical agent suitable for direct delivery to the eye which may be administered without undue toxicity. Pharmaceutically acceptable excipients include, but are not limited to, sorbitol, any of the various TWEEN compounds, and liquids such as water, saline, glycerol and ethanol. Pharmaceutically acceptable salts can be included therein, for example, mineral acid salts such as hydrochlorides, hydrobromides, phosphates, sulfates, and the like; and the salts of organic acids such as acetates, propionates, malonates, benzoates, and the like. A thorough discussion of pharmaceutically acceptable excipients is available in REMINGTON'S PHARMACEUTICAL SCIENCES (Mack Pub. Co., N.J.1991). Generally, these compositions are formulated for administration by ocular injection. Accordingly, these compositions can be combined with pharmaceutically acceptable vehicles such as saline, Ringer's balanced salt solution (pH 7.4), and the like. Although not required, the compositions may optionally be supplied in unit dosage form suitable for administration of a precise amount. Methods of Administration According to the methods of treatment of the present invention, administering of a composition comprising a therapy suitable for treating achromatopsia (ACHM) as described herein or known in the art can be accomplished by any means known in the art. According to the methods of treatment of the present invention, administering of a composition comprising a vector described herein can be accomplished by any means known in the art. According to some embodiments, the therapeutic compositions (e.g., nucleic acids encoding achromatopsia (ACHM)-associated proteins as described herein) are administered alone (i.e., without a vector for delivery). According to some embodiments, the administration is by ocular injection. According to some embodiments, the administration is by subretinal injection. Methods of subretinal delivery are known in the art. For example, see WO 2009/105690, incorporated herein by reference in its entirety. According to some embodiments, the compositions are directly injected into the subretinal space outside the central retina. In other embodiments, the administration is by intraocular injection, intravitreal injection, suprachoroidal, or intravenous injection. Administration of a vector to the retina may be unilateral or bilateral, and may be accomplished with or without the use of general anesthesia. By safely and effectively transducing ocular cells (e.g., RPE) with a composition comprising a vector described herein, wherein the vector comprises a nucleic acid encoding an achromatopsia (ACHM)-associated protein, such as CNGB3 or CNGA3, the methods of the invention may be used to treat an individual; e.g., a human, having retinal or ocular disease or disorder (e.g. ACHM), wherein the transduced cells produce an achromatopsia (ACHM)- associated protein, such as CNGB3 or CNGA3 in an amount sufficient to treat the retinal or ocular disease or disorder (e.g. ACHM). According to some embodiments, compositions may be administered by one or more subretinal injections, either during the same procedure or spaced apart by days, weeks, months, or years. According to some embodiments, multiple injections of a composition comprising a vector described herein, are no more than one hour, two hours, three hours, four hours, five hours, six hours, nine hours, twelve hours or 24 hours apart. According to some embodiments, multiple injections of a composition comprising a vector described herein, are about one month, two months, three months, four months, five months, six months, seven months, eight months, nine months, ten months, eleven months, twelve months or more apart. According to some embodiments, multiple injections of a composition comprising a vector described herein, are one year, two years, three years, four years, five years or more apart. According to some embodiments, multiple vectors may be used to treat the subject. According to the methods of treatment of the present invention, the volume of vector delivered may be determined based on the characteristics of the subject receiving the treatment, such as the age of the subject and the volume of the area to which the vector is to be delivered. It is known that eye size and the volume of the subretinal or ocular space differ among individuals and may change with the age of the subject. According to some embodiments, the volume of the composition injected to the subretinal space of the retina is more than about any one of 1 µl, 2 µl, 3 µl, 4 µl, 5 µl, 6 µl, 7 µl, 8 µl, 9 µl, 10 µl, 15 µl, 20 µl, 25 µl, 50 µl, 75 µl, 100 µl, 200 µl, 300 µl, 400 µl, 500 µl, 600 µl, 700 µl, 800 µl, 900 µl, or 1 mL, or any amount therebetween. According to embodiments wherein the vector is administered subretinally, vector volumes may be chosen with the aim of covering all or a certain percentage of the subretinal or ocular space, or so that a particular number of vector genomes is delivered. According to the methods of treatment of the present disclosure, the concentration of vector that is administered may differ depending on production method and may be chosen or optimized based on concentrations determined to be therapeutically effective for the particular route of administration. According to some embodiments, the concentration in vector genomes per milliliter (vg/ml) is selected from the group consisting of about 10 8 vg/ml, about 10 9 vg/ml, about 10 10 vg/ml, about 10 11 vg/ml, about 10 12 vg/ml, about 10 13 vg/ml, and about 10 14 vg/ml or any amount therebetween. In preferred embodiments, the concentration is in the range of 10 10 vg/ml - 10 13 vg/ml, delivered by subretinal injection or intravitreal injection in a volume of about 0.05 mL, about 0.1 mL, about 0.2 mL, about 0.4 mL, about 0.6 mL, about 0.8 mL, and about 1.0 mL. According to some embodiments, one or more additional therapeutic agents may be administered to the subject. For example, anti-angiogenic agents (e.g., nucleic acids or polypeptides) may be administered to the subject. The effectiveness of the compositions described herein can be monitored by several criteria. For example, after treatment in a subject using methods of the present disclosure, the subject may be assessed for e.g., an improvement and/or stabilization and/or delay in the progression of one or more signs or symptoms of the disease state by one or more clinical parameters including those described herein. Examples of such tests are known in the art, and include objective as well as subjective (e.g., subject reported) measures. For example, to measure the effectiveness of a treatment on a subject's visual function, one or more of the following may be evaluated: the subject's subjective quality of vision, the subject’s dark adaptation, the subject’s improved central vision function (e.g., an improvement in the subject's ability to read fluently and recognize faces), the subject's visual mobility (e.g., a decrease in time needed to navigate a maze), the subject’s visual acuity (e.g., an improvement in the subject's Log MAR score), microperimetry (e.g., an improvement in the subject's dB score), dark-adapted perimetry (e.g., an improvement in the subject's dB score), fine matrix mapping (e.g., an improvement in the subject's dB score), Goldmann perimetry (e.g., a reduced size of scotomatous area (i.e., areas of blindness) and improvement of the ability to resolve smaller targets), flicker sensitivities (e.g., an improvement in Hertz), autofluorescence, and electrophysiology measurements (e.g., improvement in ERG). According to some embodiments, the visual function is measured by the subject's dark adaptation. The Dark Adaptation Test is a test used to determine the ability of the rod photoreceptors to increase their sensitivity in the dark. This test is a measurement of the rate at which the rod and cone system recover sensitivity in the dark following exposure to a bright light source. According to some embodiments, the visual function is measured by the subject's visual mobility. According to some embodiments, the visual function is measured by the subject's visual acuity. According to some embodiments, the visual function is measured by microperimetry. According to some embodiments, the visual function is measured by dark-adapted perimetry. According to some embodiments, the visual function is measured by ERG. According to some embodiments, the visual function is measured by the subject's subjective quality of vision. VI. KITS The rAAV compositions as described herein may be contained within a kit designed for use in one of the methods of the disclosure as described herein. According to some embodiments, a kit of the disclosure comprises (a) any one of the vectors of the disclosure, and (b) instructions for use thereof. According to some embodiments, a vector of the disclosure may be any type of vector known in the art, including a non-viral or viral vector, as described supra. According to some embodiments, the vector is a viral vector, such as a vector derived from an adeno-associated virus, an adenovirus, a retrovirus, a lentivirus, a vaccinia/poxvirus, or a herpesvirus (e.g., herpes simplex virus (HSV)). According to preferred embodiments, the vector is an adeno-associated viral (AAV) vector. According to some embodiments, the kits may further comprise instructions for use. According to some embodiments, the kits further comprise a device for ocular delivery (e.g., intraocular injection, intravitreal injection, suprachoroidal, or intravenous injection) of compositions of rAAV vectors described herein. According to some embodiments, the instructions for use include instructions according to one of the methods described herein. The instructions provided with the kit may describe how the vector can be administered for therapeutic purposes, e.g., for treating a retinal or ocular disease or disorder (e.g., ACHM)). According to some embodiments wherein the kit is to be used for therapeutic purposes, the instructions include details regarding recommended dosages and routes of administration. According to some embodiments, the kits further contain buffers and/or pharmaceutically acceptable excipients. Additional ingredients may also be used, for example preservatives, buffers, tonicity agents, antioxidants and stabilizers, nonionic wetting or clarifying agents, viscosity-increasing agents, and the like. The kits described herein can be packaged in single unit dosages or in multidosage forms. The contents of the kits are generally formulated as sterile and substantially isotonic solution. All patents and publications mentioned herein are incorporated herein by reference to the extend allowed by law for the purpose of describing and disclosing the proteins, enzymes, vectors, host cells, and methodologies reported therein that might be used with the present disclosure. However, nothing herein is to be construed as an admission that the disclosure is not entitled to antedate such disclosure by virtue of prior disclosure. The present disclosure is further illustrated by the following examples, which should not be construed as further limiting. The contents of all figures and all references, patents and published patent applications cited throughout this application, as well as the Figures, are expressly incorporated herein by reference in their entirety. EXAMPLES EXAMPLE 1: Central Fundus Autofluorescence as a Predictor for Achromatopsia Therapy Fundus autofluorescence in Achromatopsia has been evaluated in relatively few studies and its significance is not quite clear. A prospective longitudinal study of retinal structure and function in achromatopsia described three patterns of fundus autofluorescence (FAF) at baseline, a normal FAF pattern a central hyperautofluorescence and a central hypoautofluorescence 1 The hypoautofluorescence pattern seems to be directly correlated to age and disease progression as characterized by SD-OCT changes at the external retina level. 1-4 However there is some controversy regarding the chronology of normal and hyperautofluorescence patterns. Fahim et al suggest that central hyperautofluorescence is associated to early stages of achromatopsia. 2 Aboshiha et al correlate more disordered SD-OCT structure to more abnormal FAF pattern (graded from normal through hyperautofluorescence to hypoautofluorescence). 1 Interestingly hyperautofluorescence group was the youngest in Aboshiha series although not statistically different. A retrospective analysis was performed in ACHM B3 Study classifying study eyes according to central autofluorescence pattern at baseline. Study eyes were classified into central hypoautofluorescence (grade 0), normal autofluorescence (grade 1), and mild or strong hyperautofluorescence (grade 2) (FIG.1). Autofluorescence grading was compared to Octopus visual field response. Results of this analysis suggest a correlation between mild and strong hyperautofluorescence and the probability of being a visual field responder. None of the six grade 0 or grade 1 eyes became visual field responders. There were six responders among the 15 grade 2 eyes (two mild and four strong hyperautofluorescence). Of note, one subject in ACHM A3 Study is considered an Octopus visual field responder and is classified as grade 2 (mild hyperautofluorescence). FIG.1 depicts representative images from a longitudinal study of retinal structure in ACHM with 50 subjects and a mean follow-up of 62 months showed no change in FAF pattern over time. 5 Subject 4029 presented stippled central hyperautofluorescence at baseline which gradually decreased after study treatment only in the study eye (FIG.2, FIG.3). EXAMPLE 2: Optical Coherence Tomography Morphology as a Predictor for Achromatopsia Therapy Some Optical Coherence Tomography (OCT) findings in Achromatopsia like foveal hypoplasia are detected in early childhood, most likely resultant of abnormal macular development. 6 However, other OCT signs like ellipsoid zone (EZ) disturbances, optical empty space (or foveal hyporeflective zone), and outer retina and retinal pigment epithelium atrophy have been associated with age suggesting a progressive natural history of this disease. 1,4,6 Important to emphasize that age is not the only variable determining disease progression and OCT findings evolution. In Yang et al. case series, the youngest subject presented the most severe foveal EZ loss. 6 Moreover, functional testing, OCT findings and age may not present a specific correlation in achromatopsia. Zobor et al. reported a case series of 36 subjects with CNGA3-related achromatopsia classifying the OCT characteristics into 5 categories: (1) continuous inner segment ellipsoid zone (EZ), (2) EZ disruption, (3) absence of EZ, (4) presence of a hyporeflective zone (HRZ), and (5) outer retinal atrophy including RPE loss. 7,8 Age distribution and functional testing results were similar among those OCT categories, except for older age in the group presenting outer retinal and RPE atrophy. Results in the literature are conflicting even for the relationship between EZ grade and foveal cone density. 9 Although the progressiveness of natural history in achromatopsia is complex open discussion, it seems reasonable to consider the presence of optical empty space (EOS) and outer retina and retinal pigment epithelium atrophy on OCT as signs of advanced disease stages. A retrospective analysis was performed in ACHM B3 and A3 Studies classifying study eyes according to OCT central outer retina morphology at baseline. Study eyes were classified into central absence of EZ line disturbance (grade 0), presence of EZ line disturbance (grade 1), or presence of empty optical space (grade 2) (FIG.4). OCT outer retina grading was compared to Octopus visual field response. Results of this analysis suggest a different distribution of OCT outer retina categories between studies. In ACHM B3 study more than two thirds of study eyes were classified as grade 0 whereas in ACHM A3 study less than a third presented the same grading (FIG.5). The fact that convincing Octopus visual field responders were mostly seen in ACHM B3 study suggest that eyes with more severe OCT findings are less likely to respond to therapy. None of two B3 subjects with Optical Empty Space are considered visual field responders. The one subject in ACHM A3 Study considered an Octopus visual field responder is classified as grade 0 (No EZ disturbance). Interestingly, some studies suggest that CNGA3-related achromatopsia might be more severe than CNGB3-related achromatopsia. 1,10,11 References 1. Aboshiha J, Dubis AM, Cowing J, Fahy RT, Sundaram V, Bainbridge JW, Ali RR, Dubra A, Nardini M, Webster AR, Moore AT, Rubin G, Carroll J, Michaelides M. A prospective longitudinal study of retinal structure and function in achromatopsia. Invest Ophthalmol Vis Sci. 2014 Aug 7;55(9):5733-43 2. Fahim AT, Khan NW, Zahid S, Schachar IH, Branham K, Kohl S, Wissinger B, Elner VM, Heckenlively JR, Jayasundera T. Diagnostic fundus autofluorescence patterns in achromatopsia. Am J Ophthalmol.2013 Dec;156(6):1211-1219. 3. Matet A, Kohl S, Baumann B, Antonio A, Mohand-Said S, Sahel JA, Audo I. Multimodal imaging including semiquantitative short-wavelength and near-infrared autofluorescence in achromatopsia Sci Rep 2018 Apr 4;8(1):5665 4. Greenberg JP, Sherman J, Zweifel SA, Chen RW, Duncker T, Kohl S, Baumann B, Wissinger B, Yannuzzi LA, Tsang SH. Spectral-domain optical coherence tomography staging and autofluorescence imaging in achromatopsia. JAMA Ophthalmol.2014 Apr 1;132(4):437-45. 5. Hirji N, Georgiou M, Kalitzeos A, Bainbridge JW, Kumaran N, Aboshiha J, Carroll J, Michaelides M. Longitudinal Assessment of Retinal Structure in Achromatopsia Patients With Long-Term Follow-up. Invest Ophthalmol Vis Sci.2018 Dec 3;59(15):5735-5744. 6. Yang P, Michaels KV, Courtney RJ, Wen Y, Greninger DA, Reznick L, Karr DJ, Wilson LB, Weleber RG, Pennesi ME. Retinal morphology of patients with achromatopsia during early childhood: implications for gene therapy. JAMA Ophthalmol.2014 Jul;132(7):823- 31. 7. Sundaram V, Wilde C, Aboshiha J, et al. Retinal structure and function in achromatopsia: implications for gene therapy. Ophthalmology.2014;121:234–245. 8. Zobor D, Werner A, Stanzial F, Benedicenti F, Rudolph G, Kellner U, Hamel C, Andréasson S, Zobor G, Strasser T, Wissinger B, Kohl S, Zrenner E; RD-CURE Consortium. The Clinical Phenotype of CNGA3-Related Achromatopsia: Pretreatment Characterization in Preparation of a Gene Replacement Therapy Trial. Invest Ophthalmol Vis Sci.2017 Feb 1;58(2):821-832. 9. Litts KM, Woertz EN, Wynne N, Brooks BP, Chacon A, Connor TB Jr, Costakos D, Dumitrescu A, Drack AV, Fishman GA, Hauswirth WW, Kay CN, Lam BL, Michaelides M, Pennesi ME, Stepien KE, Strul S, Summers CG, Carroll J. Examining Whether AOSLO-Based Foveal Cone Metrics in Achromatopsia and Albinism Are Representative of Foveal Cone Structure. Transl Vis Sci Technol.2021 May 3;10(6):22. 10. Georgiou M, Singh N, Kane T, Zaman S, Hirji N, Aboshiha J, Kumaran N, Kalitzeos A, Carroll J, Weleber RG, Michaelides M. Long-Term Investigation of Retinal Function in Patients with Achromatopsia. Invest Ophthalmol Vis Sci.2020 Sep 1;61(11):38. 11. Thiadens AA, Slingerland NW, Roosing S, et al. Genetic etiology and clinical consequences of complete and incomplete achromatopsia. Ophthalmology.2009; 116: 1984– 1989. INCORPORATION BY REFERENCE All publications, patents, and patent applications mentioned herein are hereby incorporated by reference in their entirety as if each individual publication, patent or patent application was specifically and individually indicated to be incorporated by reference. In case of conflict the present application including any definitions herein will control EQUIVALENTS Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the present invention described herein. Such equivalents are intended to be encompassed by the following claims.
INFORMAL SEQUENCE LISTING Table 1 below shows the SEQ ID NOs of the exemplary nucleic acid sequences and amino acid sequences described herein. Table 1