CNS DELIVERY BACKGROUND [1] Nucleic acids offer exciting therapeutic possibilities, including the possibility of treating otherwise untreatable diseases. SUMMARY [2] The present disclosure provides certain technologies relating to delivery of nucleic acid agents to central nervous system (“CNS”) site(s). [3] Neurological disorders pose a major challenge to the global public health. The most common neurological disorders (e.g., Alzheimer’s Disease and Parkinson’s Disease) are often associated with the central nervous system (CNS) in aging population(s). The present disclosure provides technologies that can achieve delivery of nucleic acid agents, including for treatment and/or prevention (e.g., delay of onset or exacerbation, reduction in risk of onset or exacerbation, etc.) of such neurological disorders. [4] Among other things, the present disclosure recognizes that certain extracellular vesicles, and particularly red blood cell extracellular vesicles (RBCEVs), are an attractive delivery system, e.g., for nucleic acid cargo(s) to CNS site(s). [5] Advantages that can be achieved by provided technologies include, for example, low toxicity, low cost of production, lack of immunogenicity, lack of oncogenicity, easy accessibility, simple composition, high amenability for nucleic acid loading (specifically including of long nucleic acids and/or single stranded nucleic acids, and/or RNAs). [6] The present disclosure documents that certain extracellular vesicles, and particularly red blood cell extracellular vesicles (RBCEVs) can achieve successful delivery of nucleic acid cargo(s) to CNS site(s). Among other things, the present disclosure documents robust uptake of RBCEVs by cells at CNS site(s), for example by using an in vivo imaging system to document that RBCEVs can distribute themselves along the CNS (e.g., along the brain and spinal cord), and can be retained in the CNS, including, in some embodiments, with minimal localization in the liver. [7] Among other things, the present disclosure documents uptake by various cell types in the CNS, including neurons, activated microglia, and activated astrocytes. BRIEF DESCRIPTION OF THE DRAWINGS [8] Figure 1. RBCEVs are taken up by cells in the central nervous system. Panel A. Schema of an in vivo uptake assay. C57BL/6 mice were injected with 100 μg DiR-CFSE- labelled EVs via the intrathecal route. Organs were collected for analysis 24 h post injection via optimal imaging system (IVIS®) and confocal microscopy. Panel B. Epifluorescence images of various organs collected from mice treated with 100 μg DiR-CFSE-labelled EVs at Ex745/Em800. Radiant efficiency B: brain, Gi: GI tract, H: heart, K: kidneys, Li: liver, Lu: lungs, and S: spleen. Panel C. Epifluorescence images of the vertebrae column from mice treated with 100 μg DiR-labelled EVs at Ex745/Em800. Radiant efficiency Panel D. Representative confocal microscope (z-stack) images of brain sections with Hoechst-stained nuclei, Tuj1-stained neurons, GFAP-stained astrocytes, Iba1-stained microglia and CFSE-EVs signals from cells. Scale bar, 5 μm. Created with BioRender.com. [9] Figure 2. RBCEVs delivering plasmids led to transgene expression in the central nervous system (CNS). Panel A. Schema of an in vivo assay following injection in C57BL/6 mice with 100 μg EVs loaded with CMV-luciferase plasmids. Panel B. Representative images of the mice on day 2-7, captured using IVIS®. Bioluminescence is shown in pseudo colors. Radiance (p / sec / cm2 / sr) Panels C, D, E, and F. Representative confocal microscope images of the different regions of the CNS (C: spinal cord, D: frontal lobe, E: cingulate gyrus, F: hindbrain) with Hoechst-stained nuclei, luciferase signals from cells. Scale bar, 80 μm. Created with BioRender.com. [10] Figure 3. RBCEVs delivering plasmids can be expressed by astrocytes. Panel A. Schema of an in vivo assay following injection in C57BL/6 mice with EVs loaded with GFAP-GFP plasmids. Panel B. Epifluorescence images of the brains collected from mice 48 h after an intrathecal injection of 100 μg EVs loaded with GFAP-GFP plasmids at Ex485/Em520 (n=3 mice). Radiant efficiency Panels C and D. Representative confocal microscope images brain sections with Hoechst-stained nuclei and GFP signal. Scale bar, C: 20 μm and D: 5 μm. Panel E. Schema of an ex vivo assay following incubation with EVs loaded with CMV-tdTomato plasmids. Panel F. FACS analysis of tdTomato fluorescence (PE) vs FSC-A of primary astrocytes after 48 h of incubation with 20 μg EVs loaded with CMV-tdTomato plasmids. Created with BioRender.com. [11] Figure 4. RBCEVs administered via intrathecal route are widely distributed in the vertebral column and brain tissue. Panel A. Schema of an in vivo uptake assay for DiR- CFSE-labelled RBCEVs delivered via intrathecal route. Panel B. Representative images of the untreated and treated mice’s organs captured at 24 hour timepoint. Mice were injected with 100 µg of DiR-CFSE labeled RBCEVs via intrathecal route or left untreated. Organs were harvested at 24 hour timepoint for ex-vivo imaging. DiR fluorescence is presented as pseudo-colored radiance (p / sec / cm2 / sr) . B: brain; Gi: gastrointestinal tract; H: heart; K: kidneys; Li: liver; Lu: lungs; S: spleen; VC: vertebral column. [12] Figure 5. RBCEVs are efficiently taken up by various cell types in the central nervous system. Panel A. Schema for the delivery of DiR-CFSE-labelled RBCEVs to central nervous system and immunofluorescence (IF) analysis for the uptake of RBCEVs by different cell types. Mice were injected with 100 µg of DiR-CFSE- labelled RBCEVs or left untreated in a control group. Organs were harvested at 24 hour timepoint for downstream tissue processing. Brain sections were stained with cell specific markers. Panel B. Images of brain sections stained with Tuj1 for neuronal cells. Panel C. Images of brain sections stained with GFAP for astrocytes. Panel D. Images of brain sections stained with Iba-1 for microglia. All sections were stained with Hoechst for identification of nuclei. Green fluorescence indicates CFSE signal from the cells with RBCEV uptake. Scale bar, 5 µm. [13] Figure 6. RBCEVs deliver luciferase reporter gene to the central nervous system. Panel A. Experimental schema of RBCEV-mediated delivery of luciferase reporter gene via intrathecal injection. Panel B. Representative images of the mice captured using IVIS. Mice were injected with 100 µg of luciferase plasmid loaded RBCEVs (Luc-RBCEV) or left untreated. Whole body bioluminescence images were captured on days (D) 2-7. Panel C. Representative images of the brain and spinal cord of mice harvested on day 7, captured using IVIS. Bioluminescence is shown in pseudo colors and quantified as radiance (p / sec / cm2 / sr) . [14] Figure 7. Cells in different regions of the brain express luciferase transgene delivered using RBCEVs. Representative confocal images of the cerebellum (Panel A), scale bar 50 µm; cerebral cortex (Panel B), scale bar 50 µm; and cingulate gyrus (Panel C), scale bar 20 µm; with Hoechst-stained nuclei (blue) and luciferase staining (green). [15] Figure 8. Luciferase reporter gene driven by different promoters exhibit similar levels of transgene expression. Panel A. Experimental schema to compare luciferase expression driven by different promoters following an intrathecal injection of RBCEVs loaded with different constructs. Panel B. Representative images of the mice captured using IVIS. Mice were injected with 100 µg of either CMV- or CAG-luciferase loaded RBCEVs or left untreated. Whole body bioluminescence images were captured on days (D) 3-10. Bioluminescence is shown in pseudo colors and quantified as radiance (p / sec / cm2 / sr) . Panel C. Average bioluminescence signal quantified in the mice after 3 to 14 days of treatment with 100 µg RBCEVs loaded with either CMV- or CAG-luciferase constructs (mean ± SEM; n = 3-5 mice). CMV-Luc-RBCEV and CAG-Luc-RBCEV-treated mice were compared using an unpaired t-test with Welch’s correction. Ns, non-significant. Panel D. Average weight of the mice (mean ± SEM; n = 3-5 mice). [16] Figure 9. RBCEVs deliver EGFP plasmid to the central nervous system. Panel A. Experimental schema for the delivery of RBCEVs loaded with CAG-EGFP construct . Representative confocal images of the mice’s cerebellum (Panel B) and spinal cord (Panel C) captured after 3 days of treatment. Mice were injected with 50 µg of unloaded (RBCEV only) and GFP-loaded RBCEVs or left untreated. Tissue sections were stained with Hoechst, anti-GFP antibody and cell-specific markers Calbindin (Purkinje cell), NeuN (neuronal cells) and GFAP (astrocytes). Scale bar, 50 µm. [17] Figure 10. RBCEV mediated intrathecal delivery of Nanoluc plasmid led to the secretion of Nanoluc protein. Panel A. Experimental schema of Nanoluc-RBCEV delivery and specimen collection for downstream processing. Average bioluminescence levels of NanoLuc protein in the serum (Panel B) and the cerebrospinal fluid (Panel C) of mice injected with 87 µg of unloaded (RBCEV only) and NanoLuc-loaded RBCEVs or left untreated, (n = 2-5). Average bioluminescence levels of Nanoluc protein in the spinal cord (Panel D) and brain tissue lysates (Panel E), n = 3-5 mice. All bar graphs represent mean ± SEM. * p < 0.05, ** p < 0.01 determined by Dunn’s multiple comparison test. [18] Figure 11. RBCEV mediated intrathecal delivery of GAPDH anti-sense oligonucleotide (ASO) led to the knock down of GAPDH mRNA. Panel A. Experimental Schema of GAPDH -ASO-loaded RBCEV delivery and specimen collection for downstream processing. qPCR analysis of GAPDH relative to Actin-beta (Actb) in the lumbar spinal cord (Panel B) and a part of the brain including midbrain, ventral tegmental area (VTA), substantia nigra (SN) and pons (Panel C). Mice were injected with RBCEVs containing 8 µg of NC-ASOs (negative non-targeting control) or GAPDH-ASO or left untreated (n = 3- 5). All bar graphs represent mean ± SEM. ns = non-significant; * p < 0.05; ** p < 0.01; **** p < 0.0001 determined by Dunn’s multiple comparison test. DEFINITIONS [19] About: The term “about”, when used herein in reference to a value, refers to a value that is similar, in context to the referenced value. In general, those skilled in the art, familiar with the context, will appreciate the relevant degree of variance encompassed by “about” in that context. For example, in some embodiments, the term “about” may encompass a range of values that within 25%, 20%, 19%, 18%, 17%, 16%, 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, or less of the referred value. [20] Administration: As used herein, the term “administration” typically refers to the administration of a composition to a subject or system (e.g., that is or comprises one or more cells, tissues, organisms, etc.), for example to achieve delivery of an agent that is, is included in, or is otherwise delivered by, the composition. [21] Affinity: As is known in the art, “affinity” is a measure of the tightness with which two or more binding partners associate with one another. Those skilled in the art are aware of a variety of assays that can be used to assess affinity, and will furthermore be aware of appropriate controls for such assays. In some embodiments, affinity is assessed in a quantitative assay. In some embodiments, affinity is assessed over a plurality of concentrations (e.g., of one binding partner at a time). In some embodiments, affinity is assessed in the presence of one or more potential competitor entities (e.g., that might be present in a relevant – e.g., physiological – setting). In some embodiments, affinity is assessed relative to a reference (e.g., that has a known affinity above a particular threshold [a “positive control” reference] or that has a known affinity below a particular threshold [ a “negative control” reference”]. In some embodiments, affinity may be assessed relative to a contemporaneous reference; in some embodiments, affinity may be assessed relative to a historical reference. Typically, when affinity is assessed relative to a reference, it is assessed under comparable conditions. [22] Analog: As used herein, the term “analog” refers to a substance that shares one or more particular structural features, elements, components, or moieties with a reference substance. Typically, an “analog” shows significant structural similarity with the reference substance, for example sharing a core or consensus structure, but also differs in certain discrete ways. In some embodiments, an analog is a substance that can be generated from the reference substance, e.g., by chemical manipulation of the reference substance. In some embodiments, an analog is a substance that can be generated through performance of a synthetic process substantially similar to (e.g., sharing a plurality of steps with) one that generates the reference substance. In some embodiments, an analog is or can be generated through performance of a synthetic process different from that used to generate the reference substance. [23] Associated: Two events or entities are “associated” with one another, as that term is used herein, if the presence, level, degree, type and/or form of one is correlated with that of the other. For example, a particular entity (e.g., cargo nucleic acid) is considered to be associated with a biological event (e.g., expression or activity of a polypeptide encoded by a payload nucleic acid, level of cytokine indicative of an inflammatory response, level of expression of a gene regulated by an inflammation-associated regulator, cell viability, etc.), if its presence, level and/or form correlates with incidence and/or intensity of the relevant biological event (e.g., in a cell, tissue or organism, and/or across a relevant population thereof). In some embodiments, two or more entities are physically “associated” with one another if they interact, directly or indirectly, so that they are and/or remain in physical proximity with one another. In some embodiments, two or more entities that are physically associated with one another are covalently linked to one another; in some embodiments, two or more entities that are physically associated with one another are not covalently linked to one another but are non-covalently associated, for example by means of hydrogen bonds, van der Waals interaction, hydrophobic interactions, magnetism, and combinations thereof. [24] Binding: It will be understood that the term “binding”, as used herein, typically refers to a non-covalent association between or among two or more entities. “Direct” binding involves physical contact between entities or moieties; indirect binding involves physical interaction by way of physical contact with one or more intermediate entities. Binding between two or more entities can typically be assessed in any of a variety of contexts – including where interacting entities or moieties are studied in isolation or in the context of more complex systems (e.g., while covalently or otherwise associated with a carrier entity and/or in a biological system or cell). Binding between two entities may be considered “specific” if, under the conditions assessed, the relevant entities are more likely to associate with one another than with other available binding partners. [25] Cancer: The terms "cancer", “malignancy”, "neoplasm", "tumor", and "carcinoma", are used herein to refer to cells that exhibit relatively abnormal, uncontrolled, and/or autonomous growth, so that they exhibit an aberrant growth phenotype characterized by a significant loss of control of cell proliferation. In some embodiments, a tumor may be or comprise cells that are precancerous (e.g., benign), malignant, pre-metastatic, metastatic, and/or non-metastatic. The present disclosure specifically identifies certain cancers to which its teachings may be particularly relevant. In some embodiments, a relevant cancer may be characterized by a solid tumor. In some embodiments, a relevant cancer may be characterized by a central nervous system tumor (e.g., a brain tumor, e.g., a gliobastoma). In general, examples of different types of cancers known in the art include, for example, hematopoietic cancers including leukemias, lymphomas (Hodgkin’s and non-Hodgkin’s), myelomas and myeloproliferative disorders; sarcomas, melanomas, adenomas, carcinomas of solid tissue, squamous cell carcinomas of the mouth, throat, larynx, and lung, liver cancer, genitourinary cancers such as prostate, cervical, bladder, uterine, and endometrial cancer and renal cell carcinomas, bone cancer, pancreatic cancer, skin cancer, cutaneous or intraocular melanoma, cancer of the endocrine system, cancer of the thyroid gland, cancer of the parathyroid gland, head and neck cancers, breast cancer, gastro-intestinal cancers and nervous system cancers, benign lesions such as papillomas, and the like. [26] Cargo Nucleic Acid: The term “cargo nucleic acid”, as used herein, refers to a nucleic acid that is administered or otherwise delivered to a subject or system of interest (e.g., that is or comprises one or more cells, tissues, organisms, etc). In many embodiments described herein, a cargo nucleic acid is present in and/or delivered from an extracellular vesicle (EV, e.g., a red blood cell extracellular vesicle, RBCEV). In some embodiments, a cargo nucleic acid is or comprises a payload nucleic acid. In some embodiments, a cargo nucleic acid is or comprises a promoting oligonucleotide. In some embodiments, more than one cargo nucleic acid is administered or otherwise delivered to the same subject or system in accordance with the present disclosure. In some embodiments, at least one payload nucleic acid and at least one promoting oligonucleotide are administered or otherwise delivered to the same subject or system in accordance with the present disclosure, in some embodiments as cargo within the same EV (e.g., RBCEV), in some embodiments as separate cargos within different EVs (e.g., RBCEVs) or otherwise separately. [27] Comparable: As used herein, the term “comparable” refers to two or more agents, entities, situations, sets of conditions, etc., that may not be identical to one another but that are sufficiently similar to permit comparison therebetween so that one skilled in the art will appreciate that conclusions may reasonably be drawn based on differences or similarities observed. In some embodiments, comparable sets of conditions, circumstances, individuals, or populations are characterized by a plurality of substantially identical features and one or a small number of varied features. Those of ordinary skill in the art will understand, in context, what degree of identity is required in any given circumstance for two or more such agents, entities, situations, sets of conditions, etc to be considered comparable. For example, those of ordinary skill in the art will appreciate that sets of circumstances, individuals, or populations are comparable to one another when characterized by a sufficient number and type of substantially identical features to warrant a reasonable conclusion that differences in results obtained or phenomena observed under or with different sets of circumstances, individuals, or populations are caused by or indicative of the variation in those features that are varied. [28] Corresponding to: As used herein, the term “corresponding to” refers to a relationship between two or more entities. For example, the term “corresponding to” may be used to designate the position/identity of a structural element in a compound or composition relative to another compound or composition (e.g., to an appropriate reference compound or composition). For example, in some embodiments, a monomeric residue in a polymer (e.g., an amino acid residue in a polypeptide or a nucleic acid residue in a polynucleotide) may be identified as “corresponding to” a residue in an appropriate reference polymer. For example, those of ordinary skill will appreciate that, for purposes of simplicity, residues in a polypeptide are often designated using a canonical numbering system based on a reference related polypeptide, so that an amino acid "corresponding to" a residue at position 190, for example, need not actually be the 190 ^th amino acid in a particular amino acid chain but rather corresponds to the residue found at 190 in the reference polypeptide; those of ordinary skill in the art readily appreciate how to identify "corresponding" amino acids. For example, those skilled in the art will be aware of various sequence alignment strategies, including software programs such as, for example, BLAST, CS-BLAST, CUSASW++, DIAMOND, FASTA, GGSEARCH/GLSEARCH, Genoogle, HMMER, HHpred/HHsearch, IDF, Infernal, KLAST, USEARCH, parasail, PSI-BLAST, PSI-Search, ScalaBLAST, Sequilab, SAM, SSEARCH, SWAPHI, SWAPHI-LS, SWIMM, or SWIPE that can be utilized, for example, to identify “corresponding” residues in polypeptides and/or nucleic acids in accordance with the present disclosure. Those of skill in the art will also appreciate that, in some instances, the term “corresponding to” may be used to describe an event or entity that shares a relevant similarity with another event or entity (e.g., an appropriate reference event or entity). To give but one example, a gene or protein in one organism may be described as “corresponding to” a gene or protein from another organism in order to indicate, in some embodiments, that it plays an analogous role or performs an analogous function and/or that it shows a particular degree of sequence identity or homology, or shares a particular characteristic sequence element. [29] Delivery vehicle: As used herein, the term “delivery vehicle” refers to an agent that complexes or otherwise interacts with nucleic acid for the purpose of delivering said nucleic acid to a system. Delivery vehicles may stabilize nucleic acid in otherwise harsh conditions (e.g., a bloodstream or local tissue environment after in vivo administration). Delivery vehicles may allow for nucleic acid to pass through the plasma membrane of a cell (i.e., be delivered to a cell). Furthermore, delivery vehicles may provide cell-type or tissue-type specificity in delivering of a nucleic acid. Delivery vehicles may be, for example, polyplexes, nanoconjugates, micelles, vesicles, nanocapsules, dendrimers, or nanoparticles (NPs). [30] Designed: As used herein, the term “designed” refers to an agent (i) whose structure is or was selected by the hand of man; (ii) that is produced by a process requiring the hand of man; and/or (iii) that is distinct from natural substances and other known agents. [31] Dosing regimen: Those skilled in the art will appreciate that the term “dosing regimen” may be used to refer to a set of unit doses (typically more than one) that are administered individually to a subject, typically separated by periods of time. In some embodiments, a given therapeutic agent has a recommended dosing regimen, which may involve one or more doses. In some embodiments, a dosing regimen comprises a plurality of doses each of which is separated in time from other doses. In some embodiments, individual doses are separated from one another by a time period of the same length; in some embodiments, a dosing regimen comprises a plurality of doses and at least two different time periods separating individual doses. In some embodiments, all doses within a dosing regimen are of the same unit dose amount. In some embodiments, different doses within a dosing regimen are of different amounts. In some embodiments, a dosing regimen comprises a first dose in a first dose amount, followed by one or more additional doses in a second dose amount different from the first dose amount. In some embodiments, a dosing regimen comprises a first dose in a first dose amount, followed by one or more additional doses in a second dose amount same as the first dose amount. In some embodiments, a dosing regimen is correlated with a desired or beneficial outcome when administered across a relevant population (i.e., is a therapeutic dosing regimen). [32] Engineered: In general, the term “engineered” refers to the aspect of having been manipulated by the hand of man. For example, a polynucleotide is considered to be “engineered” when two or more sequences that are not linked together in that order in nature are manipulated by the hand of man to be directly linked to one another in the engineered polynucleotide and/or when a particular residue in a polynucleotide is non-naturally occurring and/or is caused through action of the hand of man to be linked with an entity or moiety with which it is not linked in nature. In some embodiments, a cell or organism is considered to be “engineered” if it has been subjected to a manipulation, so that its genetic, epigenetic, and/or phenotypic identity is altered relative to an appropriate reference cell such as otherwise identical cell that has not been so manipulated. In some embodiments, such a manipulation is or comprises a genetic manipulation, so that its genetic information is altered (e.g., new genetic material not previously present has been introduced, for example by transformation, mating, somatic hybridization, transfection, transduction, or other mechanism, or previously present genetic material is altered or removed, for example by substitution or deletion mutation, or by mating protocols). In some embodiments, an engineered cell is one that has been manipulated so that it contains and/or expresses a particular agent of interest (e.g., a protein, a nucleic acid, and/or a particular form thereof) in an altered amount and/or according to altered timing relative to such an appropriate reference cell. As is common practice and is understood by those in the art, progeny of an engineered polynucleotide or cell are typically still referred to as “engineered” even though the actual manipulation was performed on a prior entity. [33] Expression: As used herein, the term “expression” of a nucleic acid sequence refers to the generation of any gene product from the nucleic acid sequence. In some embodiments, a gene product can be a transcript. In some embodiments, a gene product can be a polypeptide. In some embodiments, expression of a nucleic acid sequence involves one or more of the following: (1) production of an RNA template from a DNA sequence (e.g., by transcription); (2) processing of an RNA transcript (e.g., by splicing, editing, etc); (3) translation of an RNA into a polypeptide or protein; and/or (4) post-translational modification of a polypeptide or protein. [34] Homology: As used herein, the term “homology” refers to overall relatedness between polymeric molecules, e.g., between nucleic acid molecules (e.g., DNA molecules and/or RNA molecules) and/or between polypeptide molecules. In some embodiments, polymeric molecules are considered to be “substantially homologous” to one another if their sequences are at least 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 99% homologous, meaning that identical or homologous residues are present in corresponding positions of both molecules. Calculation of percent homology of two nucleic acid or polypeptide sequences, for example, can be performed by aligning two sequences for optimal comparison purposes (e.g., gaps can be introduced in one or both of a first and a second sequences for optimal alignment and non-identical sequences can be disregarded for comparison purposes). In some embodiments, a length of a sequence aligned for comparison purposes is at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or substantially 100% of length of a reference sequence; residues at corresponding positions are then compared. When a position in the first sequence is occupied by the same residue (e.g., nucleotide or amino acid) as a corresponding position in the second sequence, then the two molecules (i.e., first and second) are identical at that position. When a position in the first sequence is occupied by the same residue or by a structurally and/or functionally related residue (as will be understood by those skilled in the art, in context), then the two molecules are considered “homologous” at that position. Percent homology between two sequences is a function of the number of homologous positions shared by the two sequences being compared, taking into account the number of gaps, and the length of each gap, which needs to be introduced for optimal alignment of the two sequences. Comparison of sequences and determination of percent homology between two sequences can be accomplished using a mathematical algorithm. For example, percent homology between two nucleotide sequences can be determined using the algorithm of Meyers and Miller (CABIOS, 1989, 4: 11-17, which is herein incorporated by reference in its entirety), which has been incorporated into the ALIGN program (version 2.0). [35] “Improved,” “increased” or “reduced”: As used herein, these terms, or grammatically comparable comparative terms, indicate values that are relative to a comparable reference measurement. For example, in some embodiments, an assessed value achieved with an agent of interest may be “improved” relative to that obtained with a comparable reference agent. Alternatively or additionally, in some embodiments, an assessed value achieved in a subject or system of interest may be “improved” relative to that obtained in the same subject or system under different conditions (e.g., prior to or after an event such as administration of an agent of interest), or in a different, comparable subject (e.g., in a comparable subject or system that differs from the subject or system of interest in presence of one or more indicators of a particular disease, disorder or condition of interest, or in prior exposure to a condition or agent, etc). In some embodiments, comparative terms refer to statistically relevant differences (e.g., that are of a prevalence and/or magnitude sufficient to achieve statistical relevance). Those skilled in the art will be aware, or will readily be able to determine, in a given context, a degree and/or prevalence of difference that is required or sufficient to achieve such statistical significance. [36] Nanoparticle: As used herein, the term “nanoparticle” refers to a discrete entity of small size, e.g., typically having a longest dimension that is shorter than about 1000 nanometers (nm) and often is shorter than 500 nm, or even 100 nm or less. In many embodiments, a nanoparticle may be characterized by a longest dimension between about 1 nm and about 100 nm, or between about 1 µm and about 500 nm, or between about 1 nm and 1000 nm. In many embodiments, a population of microparticles is characterized by an average size (e.g., longest dimension) that is below about 1000 nm, about 500 nm, about 100 nm, about 50 nm, about 40 nm, about 30 nm, about 20 nm, or about 10 nm and often above about 1 nm. In many embodiments, a microparticle may be substantially spherical (e.g., so that its longest dimension may be its diameter). In some embodiments, a nanoparticle has a diameter of less than 100 nm as defined by the National Institutes of Health. In some embodiments, nanoparticles are micelles in that they comprise an enclosed compartment, separated from the bulk solution by a micellar membrane, typically comprised of amphiphilic entities which surround and enclose a space or compartment (e.g., to define a lumen). In some embodiments, a micellar membrane is comprised of at least one polymer, such as for example a biocompatible and/or biodegradable polymer. [37] Nanoparticle composition: As used herein, the term “nanoparticle composition” refers to a composition that contains at least one nanoparticle and at least one additional agent or ingredient. In some embodiments, a nanoparticle composition contains a substantially uniform collection of nanoparticles as described herein. [38] Nucleic acid: As used herein, the term “nucleic acid” refers to a polymer of at least three nucleotides. In some embodiments, a nucleic acid comprises DNA. In some embodiments comprises RNA. In some embodiments, a nucleic acid is single-stranded. In some embodiments, a nucleic acid is double-stranded. In some embodiments, a nucleic acid comprises both single- and double-stranded portions. In some embodiments, a nucleic acid comprises a backbone that comprises one or more phosphodiester linkages. In some embodiments, a nucleic acid comprises a backbone that comprises both phosphodiester and non-phosphodiester linkages. For example, in some embodiments, a nucleic acid may comprise a backbone that comprises one or more phosphorothioate or 5'-N-phosphoramidite linkages and/or one or more peptide bonds, e.g., as in a “peptide nucleic acid”. In some embodiments, a nucleic acid comprises one or more, or all, natural residues (e.g., adenine, cytosine, deoxyadenosine, deoxycytidine, deoxyguanosine, deoxythymidine, guanine, thymine, uracil). In some embodiments, a nucleic acid comprises on or more, or all, non- natural residues. In some embodiments, a non-natural residue comprises a nucleoside analog (e.g., 2-aminoadenosine, 2-thiothymidine, inosine, pyrrolo-pyrimidine, 3 -methyl adenosine, 5-methylcytidine, C-5 propynyl-cytidine, C-5 propynyl-uridine, 2- aminoadenosine, C5-bromouridine, C5-fluorouridine, C5-iodouridine, C5-propynyl-uridine, C5 -propynyl-cytidine, C5-methylcytidine, 2-aminoadenosine, 7-deazaadenosine, 7- deazaguanosine, 8-oxoadenosine, 8-oxoguanosine, 0(6)-methylguanine, 2-thiocytidine, methylated bases, intercalated bases, and combinations thereof). In some embodiments, a non-natural residue comprises one or more modified sugars (e.g., 2'-fluororibose, ribose, 2'- deoxyribose, arabinose, and hexose) as compared to those in natural residues. In some embodiments, a nucleic acid has a nucleotide sequence that encodes a functional gene product such as an RNA or polypeptide. In some embodiments, a nucleic acid has a nucleotide sequence that comprises one or more introns. In some embodiments, a nucleic acid may be prepared by isolation from a natural source, enzymatic synthesis (e.g., by polymerization based on a complementary template, e.g., in vivo or in vitro, reproduction in a recombinant cell or system, or chemical synthesis. In some embodiments, a nucleic acid is at least 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 225, 250, 275, 300, 325, 350, 375, 400, 425, 450, 475, 500, 600, 700, 800, 900, 1000, 1500, 2000, 2500, 3000, 3500, 4000, 4500, 5000 or more residues long. [39] Payload Nucleic Acid: A "payload nucleic acid" as that term is used herein refers to a nucleic acid that is administered or otherwise delivered to a subject or system of interest (e.g., that is or comprises one or more cells, tissues, organisms, etc.) that results in or is intended to achieve a particular biological result. In many embodiments described herein, a payload nucleic acid encodes an expression product (e.g., a transcript or polypeptide) that achieves or is intended to achieve the relevant result. In some embodiments described herein, a payload nucleic acid wholly or partly makes up a cargo nucleic acid. In many embodiments described herein, a payload nucleic acid is present in and/or delivered from an extracellular vesicle (EV, e.g., a red blood cell extracellular vesicle, RBCEV). In some embodiments, at least one payload nucleic acid and at least one promoting oligonucleotide are administered or otherwise delivered to the same subject or system in accordance with the present disclosure, in some embodiments as cargo within the same EV (e.g., RBCEV), in some embodiments as separate cargos within different EVs (e.g., RBCEVs) or otherwise separately. [40] Pharmaceutical composition: As used herein, the term “pharmaceutical composition” refers to an active agent, formulated together with one or more pharmaceutically acceptable carriers. In some embodiments, active agent is present in unit dose amount appropriate for administration in a therapeutic regimen that shows a statistically significant probability of achieving a predetermined therapeutic effect when administered to a relevant population. In some embodiments, pharmaceutical compositions may be specially formulated for administration in solid or liquid form, including those adapted for the following: oral administration, for example, drenches (aqueous or non- aqueous solutions or suspensions), tablets, e.g., those targeted for buccal, sublingual, and systemic absorption, boluses, powders, granules, pastes for application to the tongue; parenteral administration, for example, by subcutaneous, intramuscular, intravenous or epidural injection as, for example, a sterile solution or suspension, or sustained-release formulation; topical application, for example, as a cream, ointment, or a controlled-release patch or spray applied to the skin, lungs, or oral cavity; intravaginally or intrarectally, for example, as a pessary, cream, or foam; sublingually; ocularly; transdermally; or nasally, pulmonary, and to other mucosal surfaces [41] Promoting Oligonucleotide: As used herein, the term “promoting oligonucleotide” refers to a nucleic acid whose presence is associated with (a) increased level and/or activity of an expression product of a payload; and/or (b) decreased inflammatory and/or otherwise undesirable effect or response (e.g., immune effect or response) associated with administration or delivery of a payload nucleic acid. In some embodiments described herein, a promoting oligonucleotide wholly or partly makes up a cargo nucleic acid. In many embodiments described herein, a promoting oligonucleotide is present in and/or delivered from an extracellular vesicle (EV, e.g., a red blood cell extracellular vesicle, RBCEV). In some embodiments, at least one promoting oligonucleotide and at least one payload nucleic acid are administered or otherwise delivered to the same subject or system in accordance with the present disclosure, in some embodiments as cargo within the same EV (e.g., RBCEV), in some embodiments as separate cargos within different EVs (e.g., RBCEVs) or otherwise separately. [42] Reference: As used herein, the term “reference” describes a standard or control relative to which a comparison is performed. For example, in some embodiments, an agent, animal, individual, population, sample, sequence or value of interest is compared with a reference or control agent, animal, individual, population, sample, sequence or value. In some embodiments, a reference or control is tested and/or determined substantially simultaneously with the testing or determination of interest. In some embodiments, a reference or control is a historical reference or control, optionally embodied in a tangible medium. Typically, as would be understood by those skilled in the art, a reference or control is determined or characterized under comparable conditions or circumstances to those under assessment. Those skilled in the art will appreciate when sufficient similarities are present to justify reliance on and/or comparison to a particular possible reference or control. [43] Specific: As used herein, the term “specific”, with reference to an agent having an activity, is understood by those skilled in the art to mean that the agent discriminates between potential target entities or states. For example, and in some embodiments, an agent is said to bind “specifically” to its target if it binds preferentially with that target in the presence of one or more competing alternative targets. In many embodiments, specific interaction is dependent upon the presence of a particular structural feature of the target entity (e.g., an epitope, a cleft, a binding site). It is to be understood that specificity need not be absolute. In some embodiments, specificity may be evaluated relative to that of the binding agent for one or more other potential target entities (e.g., competitors). In some embodiments, specificity is evaluated relative to that of a reference specific binding agent. In some embodiments specificity is evaluated relative to that of a reference non-specific binding agent. In some embodiments, the agent or entity does not detectably bind to the competing alternative target under conditions of binding to its target entity. In some embodiments, binding agent binds with higher on-rate, lower off-rate, increased affinity, decreased dissociation, and/or increased stability to its target entity as compared with the competing alternative target(s). [44] Subject: As used herein, the term “subject” refers to any organism to which a provided composition is or may be administered, e.g., for experimental, diagnostic, prophylactic, cosmetic, and/or therapeutic purposes. Typical subjects include animals (e.g., mammals such as mice, rats, rabbits, non-human primates, and/or humans). In some embodiments, a subject is a human. In some embodiments, a subject is suffering from or susceptible to one or more diseases, disorders, or conditions. In some embodiments, a subject displays one or more symptoms of a disease, disorder, or condition. In some embodiments, a subject has been diagnosed with one or more diseases, disorders, or conditions. In some embodiments, the disease, disorder, or condition is or comprises cancer, or presence of one or more tumors. In some embodiments, the disease, disorder, or condition is or comprises cystic fibrosis. In some embodiments, the subject is receiving or has received certain therapy to diagnose and/or to treat a disease, disorder, or condition. [45] Therapeutically effective amount: As used herein, the term “therapeutically effective amount” means an amount of a substance (e.g., a therapeutic agent, composition, and/or formulation) that elicits a desired biological response when administered as part of a therapeutic regimen. In some embodiments, a therapeutically effective amount of a substance is an amount that is sufficient, when administered to a subject suffering from or susceptible to a disease, disorder, and/or condition, to treat, diagnose, reduce the risk of developing the disease, and/or delay the onset of the disease, disorder, and/or condition. As will be appreciated by those of ordinary skill in this art, the effective amount of a substance may vary depending on such factors as the desired biological endpoint, the substance to be delivered, the target cell or tissue, etc. For example, the effective amount of compound in a formulation to treat a disease, disorder, and/or condition is the amount that alleviates, ameliorates, relieves, inhibits, delays onset of, reduces severity of and/or reduces incidence of one or more symptoms or features of the disease, disorder, and/or condition. In some embodiments, a therapeutically effective amount is administered in a single dose; in some embodiments, multiple unit doses are required to deliver a therapeutically effective amount. [46] Unit dose: The expression “unit dose” as used herein refers to an amount administered as a single dose and/or in a physically discrete unit of a pharmaceutical composition. In many embodiments, a unit dose contains a predetermined quantity of an active agent. In some embodiments, a unit dose contains an entire single dose of the agent. In some embodiments, more than one unit dose is administered to achieve a total single dose. In some embodiments, administration of multiple unit doses is required, or expected to be required, in order to achieve an intended effect. A unit dose may be, for example, a volume of liquid (e.g., an acceptable carrier) containing a predetermined quantity of one or more therapeutic agents, a predetermined amount of one or more therapeutic agents in solid form, a sustained release formulation or drug delivery device containing a predetermined amount of one or more therapeutic agents, etc. It will be appreciated that a unit dose may be present in a formulation that includes any of a variety of components in addition to the therapeutic agent(s). For example, acceptable carriers (e.g., pharmaceutically acceptable carriers), diluents, stabilizers, buffers, preservatives, etc., may be included as described herein. It will be appreciated by those skilled in the art, in many embodiments, a total appropriate daily dosage of a particular therapeutic agent may comprise a portion, or a plurality, of unit doses, and may be decided, for example, by the attending physician within the scope of sound medical judgment. In some embodiments, the specific effective dose level for any particular subject or organism may depend upon a variety of factors including the disorder being treated and the severity of the disorder; activity of specific active compound employed; specific composition employed; age, body weight, general health, sex and diet of the subject; time of administration, and rate of excretion of the specific active compound employed; duration of the treatment; drugs and/or additional therapies used in combination or coincidental with specific compound(s) employed, and like factors well known in the medical arts. DETAILED DESCRIPTION OF CERTAIN EMBODIMENTS [47] The present disclosure, among other things, provides technologies for delivery of nucleic acids to the central nervous system. [48] In some embodiments, the present disclosure provides RBCEV preparations/populations, e.g., formulated for CNS delivery, such as by intrathecal administration. [49] The present disclosure remarkably demonstrates that provided technologies can achieve effective delivery of nucleic acids to CNS site(s), including uptake by various cell types, and expression of delivered nucleic acids. [50] In some embodiments, provided technologies can be particularly useful in the context of gene therapy applications (e.g., wherein a nucleic acid of interest, e.g., a cargo nucleic acid, is or provides gene therapy). In some embodiments, provided technologies can be particularly useful for delivery of RNAs such as, in some embodiments, RNAs that encode polypeptides usefully functional in the CNS. I. Neurological Diseases, Disorders, and Conditions [51] Technologies provided by the present disclosure achieve effective delivery of nucleic acid agents to CNS tissue and may be particularly useful in the treatment of one or more neurological diseases, disorders, and conditions. [52] In some embodiments, a neurological disease, disorder or condition may be associated with damage to CNS cells(s) and/or tissue(s). In some embodiments, a neurological disease, disorder or condition may be associated with cognitive challenges. In some embodiments, a neurological disease, disorder or condition is associated with particular structures or deposits. In some embodiments, a neurological disorder or condition is inflammatory. In some embodiments, a neurological disease, disorder or condition is or comprises genetic disorder. In some embodiments, a neurological disease, disorder or condition is associated with the spinal cord. In some embodiments, a neurological disease, disorder or condition is associated with the brain. In some embodiments, a neurological disease, disorder or condition is associated with one or more regions of the brain (for example, but not limited to, frontal lobe, cingulate gyrus, hindbrain, etc.). In some embodiments, a neurological disease, disorder or condition is associated with one or more CNS cell types (for example, but not limited to, neurons, microglia, astrocytes, etc.). In some embodiments, a neurological disease, disorder or condition is one aspect of a disease, disorder or condition that affects multiple tissues (e.g., sepsis). [53] In some embodiments, a neurological disease, disorder or condition is or comprises Alzheimer’s Disease. In some embodiments, a neurological disease, disorder or condition is or comprises Parkinson’s Disease. In some embodiments, a neurological disease, disorder or condition is or comprises cancer (e.g., one or more primary tumors and/or one or more metastases). In some embodiments, a relevant cancer is a glioma. In some embodiments, a relevant cancer is a gliobastoma. In some embodiments, a relevant metastasis is from a cancer that originated from a tissue other than the brain. In some embodiments, a relevant metastasis is from lung, breast, colorectal, kidney, melanoma, thyroid, or uterine cancer. In some embodiments, a neurological disease, disorder or condition is or comprises spinal cord damage and/or injury. In some embodiments, a neurological disease, disorder or condition is or comprises pain. In some embodiments, a neurological disease, disorder or condition is or comprises paralysis (e.g., partial and/or complete). In some embodiments, a neurological disease, disorder or condition is or comprises amyotrophic lateral sclerosis (ALS). In some embodiments, a neurological disease, disorder or condition is or comprises sepsis. In some embodiments, a neurological disease, disorder or condition is or comprises a concussion. In some embodiments, a neurological disease, disorder or condition is or comprises a traumatic brain injury (TBI). [54] The present disclosure appreciates the desirability of achieving delivery to the CNS in order to address such neurological diseases, disorders or conditions. However, the present disclosure also appreciates that various attributes and features characteristic of CNS tissues (e.g., the blood-brain barrier) can render CNS delivery particularly challenging. Indeed, many of these characteristic features are believed to represent evolutionary strategies to keep foreign materials out of the CNS, or to inactivate them if they arrive. [55] Among other things, the present disclosure describes RBCEV preparations that are particularly useful for the treatment of neurological diseases, disorders, or conditions. II. Extracellular Vesicles [56] As described herein, an extracellular vesicle (EV) is a lipid-bound vesicle-like structure. In some embodiments, EVs have a membrane. In some embodiments, EVs have a membrane that is a double layer membrane (e.g., a lipid bilayer). In some embodiments, EVs have a membrane that originates from a cell. In some embodiments, EVs have a membrane that originates from the plasma membrane of a cell. [57] The term extracellular vesicle encompasses exosomes, microvesicles, membrane microparticles, ectosomes, blebs or apoptotic bodies. In some embodiments, an EV is classified as an exosome, microvesicle, membrane microparticle, ectosome, bleb or apoptotic body based on the origin of formation. [58] In some embodiments, EVs are substantially transparent. In some embodiments, EVs are substantially spherical. Populations [59] In some embodiments, an EV population utilized in accordance with the present disclosure is characterized by an average particle diameter within a range of 50 to 1000 nm. In some embodiments, a relevant EV population is characterized by an average particle diameter within a range of 50 to 750 nm. In some embodiments, a relevant EV population is characterized by an average particle diameter within a range of 50 to 500 nm. In some embodiments, a relevant EV population is characterized by an average particle diameter within a range of 50 to 300 nm. In some embodiments, a relevant EV population is characterized by an average particle diameter within a range of 50 to 200 nm. In some embodiments, a relevant EV population is characterized by an average particle diameter within a range of 50 to 150 nm. In some embodiments, a relevant EV population is characterized by an average particle diameter within a range of 100 to 1000 nm. In some embodiments, a relevant EV population is characterized by an average particle diameter within a range of 100 to 750 nm. In some embodiments, a relevant EV population is characterized by an average particle diameter within a range of 100 to 500 nm. In some embodiments, a relevant EV population is characterized by an average particle diameter within a range of 100 to 300 nm. In some embodiments, a relevant EV population is characterized by an average particle diameter within a range of 100 to 200 nm. In some embodiments, a relevant EV population is characterized by an average particle diameter of at least 100 nm. In some embodiments, a relevant EV population is characterized by an average particle diameter of at most 300 nm. [60] In some embodiments, EVs within a population of relevant EVs have a particle diameter ranging from 50 to 1000 nm. In some embodiments, EVs within a population of relevant EVs have a particle diameter ranging from 50 to 750 nm. In some embodiments, EVs within a population of relevant EVs have a particle diameter ranging from 50 to 500 nm. In some embodiments, EVs within a population of relevant EVs have a particle diameter ranging from 50 to 300 nm. In some embodiments, EVs within a population of relevant EVs have a particle diameter ranging from 50 to 200 nm. In some embodiments, EVs within a population of relevant EVs have a particle diameter ranging from 50 to 150 nm. In some embodiments, EVs within a population of relevant EVs have a particle diameter ranging from 100 to 1000 nm. In some embodiments, EVs within a population of relevant EVs have a particle diameter ranging from 100 to 750 nm. In some embodiments, EVs within a population of relevant EVs have a particle diameter ranging from 100 to 500 nm. In some embodiments, EVs within a population of relevant EVs have a particle diameter ranging from 100 to 300 nm. In some embodiments, EVs within a population of relevant EVs have a particle diameter ranging from 100 to 200 nm. In some embodiments, EVs within a population of relevant EVs have a particle diameter of at least 100 nm. In some embodiments, EVs within a population of relevant EVs have a particle diameter of at most 300 nm. [61] A population of EVs (e.g., as may be present in and/or used to manufacture a composition, pharmaceutical composition, medicament, preparation or otherwise) may include EVs with a range of diameters. In some embodiments, the median diameter of EVs within a population is 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, or 300 nm (± 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 nm). In some embodiments, the mean diameter of EVs within a population is 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, or 300 nm (± 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 nm). [62] A population of EVs may comprise at least 10, 100, 1000, 10 ⁴ , 10 ⁵ , 10 ⁶ , 10 ⁷ , 10 ⁸ , 10 ⁹ , 10 ¹⁰ , 10 ¹¹ , 10 ¹² , 10 ¹³ or 10 ¹⁴ EVs. A population of EVs may comprise at least 10, 100, 1000, 10 ⁴ , 10 ⁵ , 10 ⁶ , 10 ⁷ , 10 ⁸ , 10 ⁹ , 10 ¹⁰ , 10 ¹¹ , 10 ¹² , 10 ¹³ or 10 ¹⁴ EVs per mL of carrier. Red Blood Cell Derived Extracellular Vesicles (RBCEVs) [63] In some embodiments, EVs are derived from red blood cells. In some embodiments, EVs are red blood cell derived extracellular vesicles (RBCEVs). In some embodiments, EVs are derived from red blood cells ex vivo from a blood draw from a subject. [64] Red blood cells (e.g, erythrocytes) are enucleated. Red blood cells are characterized in that they do not contain DNA or they contain substantially no DNA. Red blood cells may contain miRNAs or other RNAs. Red blood cells do not contain oncogenic DNA or oncogenic DNA mutations. Red blood cells lack cellular organelles, such as endosomes and endoplasmic reticulum. Red blood cells cannot produce exosomes. [65] In some embodiments, RBCEVs contain less nucleic acid than EVs that have been derived from other cell types. In some embodiments, RBCEVs do not contain nucleic acid (e.g., DNA) that was present in the cells from which they were derived. In some embodiments, RBCEVs are non-exosomal EVs. [66] In some embodiments, RBCEVs comprise hemoglobin, stomatin, and/or flotilin-2. In some embodiments, RBCEVs are red in color. In some embodiments, RBCEVs are substantially transparent. In some embodiments, RBCEVs exhibit a domed (i.e., concave) surface, or “cup shape” when viewed under transmission electron microscopes. In some embodiments, RBCEVs comprise cell surface CD235a. [67] In some embodiments, an RBCEV population is characterized by an average particle diameter within a range of 50 to 1000 nm. In some embodiments, an RBCEV population is characterized by an average particle diameter within a range of 50 to 750 nm. In some embodiments, an RBCEV population is characterized by an average particle diameter within a range of 50 to 500 nm. In some embodiments, an RBCEV population is characterized by an average particle diameter within a range of 50 to 300 nm. In some embodiments, an RBCEV population is characterized by an average particle diameter within a range of 50 to 200 nm. In some embodiments, an RBCEV population is characterized by an average particle diameter within a range of 50 to 150 nm. In some embodiments, an RBCEV population is characterized by an average particle diameter within a range of 100 to 1000 nm. In some embodiments, an RBCEV population is characterized by an average particle diameter within a range of 100 to 750 nm. In some embodiments, an RBCEV population is characterized by an average particle diameter within a range of 100 to 500 nm. In some embodiments, an RBCEV population is characterized by an average particle diameter within a range of 100 to 300 nm. In some embodiments, an RBCEV population is characterized by an average particle diameter within a range of 100 to 200 nm. In some embodiments, an RBCEV population is characterized by an average particle diameter of at least 100 nm. In some embodiments, an RBCEV population is characterized by an average particle diameter of at most 300 nm. [68] In some embodiments, RBCEVs within a population of RBCEVs have a particle diameter ranging from 50 to 1000 nm. In some embodiments, RBCEVs within a population of RBCEVs have a particle diameter ranging from 50 to 750 nm. In some embodiments, RBCEVs within a population of RBCEVs have a particle diameter ranging from 50 to 500 nm. In some embodiments, RBCEVs within a population of RBCEVs have a particle diameter ranging from 50 to 300 nm. In some embodiments, RBCEVs within a population of RBCEVs have a particle diameter ranging from 50 to 200 nm. In some embodiments, RBCEVs within a population of RBCEVs have a particle diameter ranging from 50 to 150 nm. In some embodiments, RBCEVs within a population of RBCEVs have a particle diameter ranging from 100 to 1000 nm. In some embodiments, RBCEVs within a population of RBCEVs have a particle diameter ranging from 100 to 750 nm. In some embodiments, RBCEVs within a population of RBCEVs have a particle diameter ranging from 100 to 500 nm. In some embodiments, RBCEVs within a population of RBCEVs have a particle diameter ranging from 100 to 300 nm. In some embodiments, RBCEVs within a population of RBCEVs have a particle diameter ranging from 100 to 200 nm. In some embodiments, RBCEVs within a population of RBCEVs have a particle diameter of at least 100 nm. In some embodiments, RBCEVs within a population of RBCEVs have a particle diameter of at most 300 nm. [69] A population of RBCEVs (e.g., as present in a composition, pharmaceutical composition, medicament, preparation or otherwise) will comprise RBCEVs with a range of diameters. In some embodiments, the median diameter of RBCEVs within a population is 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, or 300 nm (± 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 nm). In some embodiments, the mean diameter of RBCEVs within a population is 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, or 300 nm (± 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 nm). [70] A population of RBCEVs may comprise at least 10, 100, 1000, 10 ⁴ , 10 ⁵ , 10 ⁶ , 10 ⁷ , 10 ⁸ , 10 ⁹ , 10 ¹⁰ , 10 ¹¹ , 10 ¹² , 10 ¹³ or 10 ¹⁴ RBCEVs. A population of RBCEVs may comprise at least 10, 100, 1000, 10 ⁴ , 10 ⁵ , 10 ⁶ , 10 ⁷ , 10 ⁸ , 10 ⁹ , 10 ¹⁰ , 10 ¹¹ , 10 ¹² , 10 ¹³ or 10 ¹⁴ RBCEVs per mL of carrier. [71] In some embodiments, RBCEVs are derived from a human or animal blood sample. In some embodiments, RBCEVs are derived from red blood cells derived from primary cells or immobilized red blood cell lines. In some embodiments, RBCEVs are derived from blood cells type matched to the subject that is to be treated. In some embodiments, RBCEVs are derived from blood cells of Group A, Group B, Group AB, or Group O blood. In some embodiments, RBCEVs are derived from blood cells of Group O blood. [72] In some embodiments, blood (e.g., blood in which RBCEVs are to be derived from) is any blood type. In some embodiments, blood is rhesus positive or rhesus negative. In some embodiments, blood is Group O and/or rhesus negative, such as Type O-. In some embodiments, blood has been determined to be free from disease or disorder. For example, in some embodiments, blood has been determined to be free from HIV, HBV, HCV, syphilis, sickle cell anemia, SARS-CoV2, and/or malaria. [73] In some embodiments, RBCEVs are derived from a blood sample obtained from a subject that is to be treated. In some embodiments, RBCEVs are autologous. In some embodiments, RBCEVs are derived from a blood sample obtained from a subject other than one that is to be treated. In some embodiments, RBCEVs are allogenic. [74] In some embodiments, RBCEVs are isolated from a sample of red blood cells. Protocols for obtaining EVs from red blood cells are known in the art, for example in Danesh et al. (2014) Blood.2014 Jan 30; 123(5): 687–696. Methods useful for obtaining RBCEVs may include steps of providing or obtaining a sample comprising red blood cells, inducing the red blood cells to produce EVs, and isolating the EVs. A sample may be a whole blood sample. Red blood cells in a sample may be separated from other components of a whole blood sample (e.g., white blood cells or plasma). Red blood cells may be concentrated (e.g., by centrifugation). A blood sample may be subjected to leukocyte reduction. [75] Cells other than red blood cells may have been removed from the sample, such that the cellular component of the sample is entirely or substantially only red blood cells. In some embodiments, EVs are induced from red blood cells by contacting the cells with a vesicle-inducing agent. In some embodiments, a vesicle-inducing agent is calcium ionophore, lysophosphatidic acid (LPA), or phorbol-12-myristat-13-acetate (PMA). In some embodiments, a vesicle-inducing agent is about 10 nM calcium ionophore. [76] In some embodiments, RBCEVs are isolated from red blood cells and other components of a sample and/or mixture. In some embodiments, RBCEVs are isolated by centrifugation (with or without ultracentrifugation), precipitation, filtration (e.g., tangential flow filtration), or chromatography. [77] In some embodiments, red blood cells are separated from a whole blood sample which contains white blood cells and plasma by low speed centrifugation and leukodepletion filters. In some embodiments, a red blood cell sample comprises no other cell types (e.g., white blood cells). In some embodiments, red blood cells are diluted in buffer (e.g., PBS) prior to contacting with a vesicle-inducing agent. In some embodiments, red blood cells are contacted with a vesicle-inducing agent overnight, or for at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12 or more than 12 hours. In some embodiments, red blood cells are contacted with a vesicle- inducing agent at a plurality of time points. In some embodiments, RBCEVs are isolated by subjecting a sample to low speed centrifugation and/or passing a sample through an about 0.45 μm syringe filter. In some embodiments, RBCEVs are concentrated by ultracentrifugation. In some embodiments, RBCEVs are concentrated by ultracentrifugation at a speed of 10,000 x g, 15,000 x g, 20,000 x g, 25,000 x g, 30,000 x g, 40,000 x g, 50,000 x g, 60,000 x g, 70,000 x g, 80,000 x g, 90,000 x g or 100,000 x g. In some embodiments, RBCEVs are concentrated by ultracentrifugation at a speed within a range of 10,000 x g and 50,000 x g. In some embodiments, RBCEVs are concentrated by ultracentrifugation at a speed of about 15,000 x g. In some embodiments, RBCEVs are concentrated by ultracentrifugation for at least 10 minutes, at least 20 minutes, at least 30 minutes, at least 40 minutes, at least 50 minutes or at least one hour. [78] In some embodiments, concentrated RBCEVs are suspended in cold PBS. In some embodiments, concentrated RBCEVs are layered on a sucrose cushion. In some embodiments, a sucrose cushion comprises frozen 60% sucrose. In some embodiments, RBCEVs layered on a sucrose cushion are subjected to ultracentrifugation at 100,000 x g for at least 1 hour, at least 2 hours, at least 3 hours, at least 4 hours, at least 5 hours, at least 6 hours, at least 7 hours, at least 8 hours, at least 9 hours, at least 10 hours, at least 11 hours, at least 12 hours, at least 13 hours, at least 14 hours, at least 15 hours, at least 16 hours, at least 17 hours, at least 18 hours or longer. In some embodiments, RBCEVs layered on a sucrose cushion are subjected to ultracentrifugation at 100,000 x g for about 16 hours. RBCEVs may then be obtained by collecting the red layer above the sucrose cushion. [79] Methods for isolation and characterization of RBCEVs are described, for example, in Usman et al. (Efficient RNA drug delivery using red blood cell extracellular vesicles. Nature Communications 9, 2359 (2018) doi:10.1038/s41467-018-04791-8), incorporated herein in its entirety by reference. Production [80] Typically, EVs are produced by budding, and/or shedding off of a parent cell. An extracellular vesicle may be derived from various cell types. In some embodiments, EVs have a similar composition to the cell from which it is derived from (e.g., as characterized by the type and/or amount of proteins in the lumen and/or associated with the membrane). In some embodiments, an EV is produced from outward budding and fission of cellular membrane. An EV may be produced via a natural process or a chemically-induced or enhanced process. [81] In some embodiments, EVs are produced from cells that are contacted with a vesicle- inducing agent. A vesicle-inducing agent may be calcium ionophore, lysophosphatidic acid (LPA), or phorbol-12-myristat-13-acetate (PMA). [82] In some embodiments, EVs are produced from human cells, or cells of human origin. In some embodiments, EVs are produced from cells that are not modified (e.g., transduced, transfected, infected, or otherwise modified). In some embodiments, EVs are produced from cells that are ex vivo. [83] In some embodiments, EVs are produced from hematopoietic cells. In some embodiments, EVs are produced from immune cells. For example, EVs may be produced from red blood cells, white blood cells, cancer cells, stem cells, dendritic cells, macrophages, or other cell types. [84] In some embodiments, EVs are produced from red blood cells which have been isolated from plasma and white blood cells. Red blood cells may be isolated by centrifugation and/or leukodepletion filters. In some embodiments, EVs are produced from red blood cells by contacting the cells with calcium ionophore for a sufficient period of time. In some embodiments, contacting red blood cells with calcium ionophore overnight (e.g., 12 hours) is a sufficient period of time to produce EVs. [85] In some embodiments, EVs are purified from red blood cells and cellular debris. In some embodiments, EVs are purified from red blood cells and cellular debris by centrifugation. In some embodiments, purified EVs are stored at −80 °C. [86] In some embodiments, an EV is a microvesicle or membrane microparticle produced via chemical induction. In some embodiments, a microvesicle or membrane microparticle is shed from the plasma membrane of a cell and does not originate from the endosomal system. [87] In some embodiments of the present disclosure, an EV selected for loading with cargo nucleic acid is not an exosome. In some embodiments, an EV selected for loading with cargo nucleic acid is not an ectosome. In some embodiments, an EV selected for loading with cargo nucleic acid is not a bleb. In some embodiments, an EV selected for loading with cargo nucleic acid is not an apoptotic body. III. Cargo Nucleic Acids [88] As described herein, a cargo nucleic acid is a nucleic acid that is administered or otherwise delivered to a subject or system of interest (e.g., that is or comprises one or more cells, tissues, organisms, etc.). [89] Various aspects of the present disclosure relate to nucleic acid agents (e.g., to cargo nucleic acids such as payload nucleic acids and/or promoting oligonucleotides as described herein). Those skilled in the art will appreciate, reading the present disclosure, that many of its findings are applicable to a variety of different nucleic acid agents (as reviewed, for example, in Roberts, et al., "Advances in oligonucleotide drug delivery." Nature Reviews Drug Discovery 19.10 (2020) and hereby incorporated by reference in its entirety). [90] In some embodiments, a nucleic acid agent comprises DNA. In some embodiments, a nucleic acid agent comprises RNA. In some embodiments, a nucleic acid agent is single- stranded. In some embodiments, a nucleic acid agent is double-stranded. In some embodiments, a nucleic acid comprises both single- and double-stranded portions. In some embodiments, a strand of a nucleic acid agent comprises self-complementary element(s) such that one or more double-stranded structures can form by self-hybridization within the strand. [91] In some embodiments, a nucleic acid comprises a backbone that comprises one or more phosphodiester linkages. In some embodiments, a nucleic acid comprises a backbone that comprises both phosphodiester and non-phosphodiester linkages. For example, in some embodiments, a nucleic acid may comprise a backbone that comprises one or more phosphorothioate or 5'-N-phosphoramidite linkages and/or one or more peptide bonds, e.g., as in a “peptide nucleic acid”. [92] In some embodiments, a nucleic acid comprises one or more, or all, natural residues (e.g., adenine, cytosine, deoxyadenosine, deoxycytidine, deoxyguanosine, deoxythymidine, guanine, thymine, uracil). In some embodiments, a nucleic acid comprises on or more, or all, non-natural residues. In some embodiments, a non-natural residue comprises a nucleoside analog (e.g., 2-aminoadenosine, 2-thiothymidine, inosine, pyrrolo-pyrimidine, 3 - methyl adenosine, 5-methylcytidine, C-5 propynyl-cytidine, C-5 propynyl-uridine, 2- aminoadenosine, C5-bromouridine, C5-fluorouridine, C5-iodouridine, C5-propynyl-uridine, C5 -propynyl-cytidine, C5-methylcytidine, 2-aminoadenosine, 7-deazaadenosine, 7- deazaguanosine, 8-oxoadenosine, 8-oxoguanosine, 0(6)-methylguanine, 2-thiocytidine, methylated bases, intercalated bases, and combinations thereof), an intercalator (e.g., acridine, psoralen, etc.), or a chelator (e.g., metals, radioactive metals, boron, oxidative metals, etc.). In some embodiments, a non-natural residue comprises one or more modified sugars (e.g., 2'-fluororibose, ribose, 2'-deoxyribose, 2’-amino (2’-NH), 2’-O-methyl (2’- OMe), arabinose, and hexose) as compared to those in natural residues. In some embodiments, a non-natural residue comprises one or more modified bases (e.g., 5-position pyrimidine modifications, 8-position purine modifications, modifications at exocyclic amines, substitution of 4-thiouridine, substitution of 5-bromo- or 5-iodo-uracil, backbone modifications, methylations, unusual base-pairing combinations such as the isobases isocytidine and isoguanidine) as compared to those in natural residues. In some embodiments, a non-natural residue comprises one or more 3’ and 5’ modifications (e.g., capping) as compared to those in natural residues. Further, any of the hydroxyl groups ordinarily present in a sugar may be replaced by a phosphonate group or a phosphate group; protected by standard protecting groups; or activated to prepare additional linkages to additional nucleotides or to a solid support. The 5' and 3' terminal OH groups can be phosphorylated or substituted with amines, organic capping group moieties of from about 1 to about 20 carbon atoms, or organic capping group moieties of from about 1 to about 20 polyethylene glycol (PEG) polymers or other hydrophilic or hydrophobic biological or synthetic polymers. Nucleic acids may be of variant types, such as locked nucleic acid (LNA), peptide nucleic acid (PNA), or gapmer. [93] In some embodiments, a nucleic acid has a nucleotide sequence that encodes a functional gene product such as an RNA or polypeptide. In some embodiments, a nucleic acid has a nucleotide sequence that comprises one or more introns. In some embodiments, a nucleic acid may be prepared by isolation from a natural source, enzymatic synthesis (e.g., by polymerization based on a complementary template, e.g., in vivo or in vitro, reproduction in a recombinant cell or system, or chemical synthesis. In some embodiments, a nucleic acid is at least 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 225, 250, 275, 300, 325, 350, 375, 400, 425, 450, 475, 500, 600, 700, 800, 900, 1000, 1500, 2000, 2500, 3000, 3500, 4000, 4500, 5000 or more residues long. [94] Nucleic acid agents, generally, can be super-coiled or not super-coiled. Nucleic acid agents, generally, can be chromosomal or non-chromosomal. Nucleic acid agents may be linear or circular. Nucleic acid agents may be conjugated to, or complexed with, other molecules (e.g., carriers, stabilizers, histones, lipophilic agent, etc.). [95] In some embodiments, a cargo nucleic acid is present in and/or delivered from a delivery vehicle. In many embodiments described herein, a cargo nucleic acid is present in and/or delivered from an extracellular vesicle (EV, e.g., an RBCEV). In some embodiments, one or more copies of an identical cargo nucleic acid is present in and/or delivered from an extracellular vesicle (EV, e.g., an RBCEV). In some embodiments, two or more non-identical cargo nucleic acids are present in and/or delivered from the same extracellular vesicle (EV, e.g., an RBCEV). One of ordinary skill in the art will appreciate that cargo nucleic acids may be non-identical for a various reasons (e.g., sequence, strandedness; length, chemical composition and/or modification, etc.). [96] In some embodiments, a cargo nucleic acid is or comprises a payload nucleic acid. In some embodiments, a cargo nucleic acid is or comprises a promoting oligonucleotide. In some embodiments, more than one cargo nucleic acid is administered or otherwise delivered to the same subject or system in accordance with the present disclosure. In some embodiments, at least one payload nucleic acid and at least one promoting oligonucleotide are administered or otherwise delivered to the same subject or system in accordance with the present disclosure, in some embodiments as cargo within the same EV (e.g., RBCEV), in some embodiments as separate cargos within different EVs (e.g., RBCEVs) or otherwise separately. Payload Nucleic Acids [97] As described herein, a payload nucleic acid is a nucleic acid that is administered or otherwise delivered to a subject or system of interest (e.g., that is or comprises one or more cells, tissues, organisms, etc.) that results in or is intended to achieve a particular biological result. In many embodiments described herein, a payload nucleic acid encodes an expression product (e.g., a transcript or polypeptide) that achieves or is intended to achieve the relevant result. [98] Teachings of the present disclosure relate to payload nucleic acids that are not intended for use with viral vectors. In some embodiments, a payload nucleic acid does not comprise ITR sequences. [99] In some embodiments, a payload nucleic acid may be delivered to at least one cell type or tissue within a subject or system of interest. In some embodiments, a payload nucleic acid expresses or is intended to express an expression product within the cell type or tissue in which it was delivered. In some embodiments, a payload nucleic acid expresses or is intended to express an expression product which is subsequently secreted and/or released from the cell type or tissue in which it was delivered. [100] In some embodiments, a payload nucleic acid is therapeutic to a subject or system of interest in which the payload nucleic acid was administered. In some embodiments, a payload nucleic acid is therapeutic to one or more cell types or tissues in which the payload nucleic acid was delivered. In some embodiments, a payload nucleic acid is therapeutic to one or more cell types or tissues other than in which the payload nucleic acid was delivered. [101] In some embodiments, a payload nucleic acid is or comprises DNA that encodes an expression product. [102] In some embodiments, a payload nucleic acid that is or comprises DNA has a maximum size of 30,000 kb. A payload nucleic acid that is or comprises DNA may have a size of about 30,000, 25,000, 20,000, 15,000, 10,000, 9,000, 8,000, 7,000, 6,000, 5,000, 4,000, 3,000, 2,000, 1,000 or less kb. [103] In some embodiments, a payload nucleic acid is or comprises RNA that encodes an expression an expression product. [104] In some embodiments, a payload nucleic acid that is or comprises RNA has a maximum size of 2,000 kb. A payload nucleic acid that is or comprises RNA may have a size of about 2,000, 1,500, 1,000, 900, 800, 700, 600, 500, 400, 300, 200, 100 or less kb. [105] In some embodiments, a payload nucleic acid is or comprises a DNA plasmid, an RNA plasmid, a circular DNA, a linear double-stranded DNA, a DNA minicircle, a dumbbell-shaped DNA minimal vector, a doggy bone vector, a closed-end linear DNA vector, a nicked linear DNA vector, an RNA minicircle, a small interfering RNA (siRNA), a messenger RNA (mRNA), a guide RNA (gRNA), a prime editing guide RNA (peg RNA), a CRISPR RNA (crRNA), a trans-activating CRISPR RNA (tracrRNA), a circular RNA, a microRNA (miRNA), a primary miRNA (pri-miRNA), a precursor miRNA (pre-miRNA), a piwi-interacting RNA (piRNA), a transfer RNA (tRNA), a long noncoding RNA (lncRNA), an antisense oligonucleotide (ASO), a short hairpin RNA (shRNA), a small activating RNA (saRNA), a small nucleolar RNAs (snoRNA), a gapmer, a locked nucleic acid (LNA), a peptide nucleic acid (PNA), or an expression vector. [106] In some embodiments, a payload nucleic acid is or comprises a minicircle. Minicircles are circular replicons around 4 kbp. In some embodiments, a minicircle is or comprises DNA. In some embodiments, a minicircle is or comprises RNA. In some embodiments, a minicircle is double-stranded or comprises double-stranded regions. In some embodiments, a minicircle is synthetically derived. In some embodiments, a minicircle does not comprise an origin of replication and therefore does not replicate within a cell. In some embodiments, a minicircle is or comprises a reporter gene. Minicircles are known to those of ordinary skill in the art (e.g. see Gaspar et al., Expert Opin Biol Ther 15(3), 2015 incorporated by reference in its entirety herein). [107] In some embodiments, a payload nucleic acid is or comprises a dumbbell-shaped DNA minimal vector. A dumbbell-shaped DNA minimal vector is or comprises a DNA oligonucleotide with a secondary structure comprising one or more hairpins. Dumbbell- shaped DNA minimal vectors are described, for example, in Yu et al (Nucleic Acids Research 2015: 43(18): e120), Jiang et al (Molecular Therapy 2016: 24(9): 1581-1591) and Zanta et al (PNAS 1999: 96: 91-96), each incorporated herein by reference in its entirety. [108] In some embodiments, a payload nucleic acid is or comprises a doggy bone vector. In some embodiments, a payload nucleic acid is or comprises a closed-end linear DNA vector. In some embodiments, a payload nucleic acid is or comprises a nicked linear DNA vector. [109] In some embodiments, a payload nucleic acid is or comprises a plasmid. In some embodiments, a plasmid is able to replicate independently in a cell. In some embodiments, a plasmid comprises an origin of replication sequence. In some embodiments, a plasmid is a nanoplasmid. [110] In some embodiments, a payload nucleic acid is or comprises RNA. In some embodiments, a payload nucleic acid is or comprises therapeutic RNA. In some embodiments, a payload nucleic acid is or comprises RNA that encodes an expression product (e.g., one or more polypeptides or antigen-binding molecules). In some embodiments, a payload nucleic acid is or comprises RNA that comprises a sequence complementary to a nucleic acid sequence endogenous to a cell in which the payload nucleic acid is delivered. In some embodiments, a payload nucleic acid is or comprises RNA that is useful in methods of gene silencing or downregulating gene expression. [111] In some embodiments, a payload nucleic acid is antisense to an endogenous nucleic acid sequence within a cell. In some embodiments, an antisense nucleic acid is single or double-stranded. In some embodiments, an antisense nucleic acid comprises double- stranded RNA (dsRNA) or partially double-stranded RNA that is complementary to a target nucleic acid sequence. In some embodiments, a double-stranded RNA molecule is formed by the complementary pairing between a first RNA portion and a second RNA portion within an antisense nucleic acid. The length of an RNA sequence (i.e. one portion) may be less than 30 nucleotides in length (e.g., 29, 28, 27, 26, 25, 24, 23, 22, 21, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10 or fewer nucleotides). In some embodiments, the length of an RNA sequence is within a range of about 18-24 nucleotides. [112] In some embodiments, a complementary first RNA portion and a second RNA portion form a “stem” of a hairpin structure. The two portions can be joined by a linking sequence, which may form the “loop” in the hairpin structure. The linking sequence can vary in length and may be, for example, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or more nucleotides in length. Suitable linking sequences are known in the art. [113] In some embodiments, an antisense nucleic acid hybridizes to a corresponding DNA sequence within a cell. An antisense nucleic acid may hybridize to a corresponding mRNA within a cell, forming a double-stranded molecule. An antisense nucleic acid may interfere or otherwise disrupt translation of a complementary mRNA, as translation of double- stranded mRNA does not occur. Antisense inhibition of translation is known in the art (see, e.g., Marcus-Sakura, Anal. Biochem.1988, 172:289). [114] In some embodiments, an antisense nucleic acid hybridizes to a corresponding micro RNA (miRNA). In some embodiments, an antisense nucleic acid inhibits the function of a miRNA and/or prevents the miRNA from post-transcriptionally regulating gene expression. In some embodiments, an antisense nucleic acid functions to upregulate expression of one or more genes that are otherwise downregulated by a miRNA. In some embodiments, an antisense nucleic acid functions to downregulate expression of target genes. [115] Examples of an antisense nucleic acid include, but are not limited to, small interfering RNA (siRNA; including derivatives or pre-cursors, such as nucleotide analogs), short hairpin RNA (shRNA), micro RNA (miRNA), saRNA (small activating RNA), small nucleolar RNA (snoRNA) or derivatives or pre-cursors, long non-coding RNA (lncRNA), or single stranded molecules such as chimeric ASO or gapmers. In some embodiments, an antisense nucleic acid stimulates RNA interference (RNAi) or other cellular degradation mechanisms (e.g., RNase degradation). [116] In some embodiments, a payload nucleic acid is or comprises a siRNA. A "siRNA," "small interfering RNA," "small RNA," or "RNAi" as provided herein, refers to a nucleic acid that forms a double-stranded RNA, which double-stranded RNA has the ability to reduce or inhibit expression of a gene or target gene when expressed in the same cell as the gene or target gene. Complementary portions of RNA that hybridize to form double- stranded RNA may have substantially or completely complementary sequences. In some embodiments, a siRNA has a sequence that is substantially or completely complementary to a target gene sequence. In some embodiments, a siRNA has a length within a range of about 15-50 nucleotides (e.g., each complementary sequence of double-stranded siRNA is about 15-50 nucleotides in length and the double-stranded siRNA is about 15-50 base pairs in length). A siRNA may have a length within a range of 20-30 nucleotides, 20-25 nucleotides, or 24-29 nucleotides (e.g., 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 nucleotides in length). RNAi and siRNA are described in, for example, Dana et al., Int J Biomed Sci.2017; 13(2): 48–57, herein incorporated by reference in its entirety. [117] Suitable siRNA molecules for use in the methods of the present invention may be designed by schemes known in the art (see, for example, Elbashire et al., Nature, 2001 411:494-8; Amarzguioui et al., Biochem. Biophys. Res. Commun.2004316(4):1050-8; and Reynolds et al., Nat. Biotech.2004, 22(3):326-30). In some embodiments, siRNA molecules are designed and/or found from commercial vendors. (e.g., Ambion, Dharmacon, GenScript, Invitrogen OligoEngine, etc.). A potential siRNA candidate may be checked for possible complementation and/or interaction with other nucleic acid sequences or polymorphisms using a BLAST alignment program (see, for example, the National Library of Medicine website). In some embodiments, a number of siRNAs are generated and screened to obtain a potential candidate (see, for example, U.S. Pat. No.7,078,196). In some embodiments, a siRNA is expressed from a vector and/or produced chemically or synthetically. Synthetic RNAi may be obtained from commercial sources, for example, Invitrogen (Carlsbad, California). RNAi vectors may be obtained from commercial sources, for example, Invitrogen. [118] In some embodiments, a payload nucleic acid is or comprises a miRNA. The term "miRNA" is used in accordance with its ordinary meaning and refers to a small non-coding RNA molecule capable of post-transcriptionally regulating gene expression. In some embodiments, a miRNA is a nucleic acid that has substantial or complete identity to a target gene. In some embodiments, a miRNA inhibits gene expression by interacting with a complementary cellular mRNA thereby interfering with the expression of the complementary mRNA. In some embodiments, a miRNA has a length within a range of about 15-50 nucleotides. (e.g., each complementary sequence of miRNA is about 15-50 nucleotides in length and double-stranded miRNA is about 15-50 base pairs in length). In some embodiments, a miRNA comprises a stem-loop and/or hairpin structure. In some embodiments, a miRNA is synthetic or recombinant. In some embodiments, a miRNA is associated with cancer. In some embodiments, a miRNA is miR-125b. [119] In some embodiments, a payload nucleic acid is or comprises an expression vector or expression cassette sequence. The terms expression vector or expression cassette sequence refer to a nucleic acid molecule used to express exogenous nucleic acid within a cell. Suitable expression vectors and expression cassettes are known in the art. Expression vectors may comprise elements that facilitate the expression of one or more nucleic acid sequences in a target system (e.g. cell, tissue, organism, etc.). [120] In some embodiments, an expression vector comprises a promoter sequence operably linked to the nucleotide sequence encoding the nucleic acid sequence to be expressed. In some embodiments, an expression vector comprises a termination codon. In some embodiments, an expression vector comprises expression enhancers. Suitable promoters, termination codons, and enhancers may be used and are known in the art. [121] In some embodiments, a payload nucleic acid is or comprises a plurality of expression vectors encoding for different peptides or proteins. The different peptides or proteins may be interrelated, such as subunits or components of the same molecule, or molecules that have an interlinked operation, such as components of the same biological pathways, or exhibit a ligand:receptor binding relationship. [122] In some embodiments, a payload nucleic acid is or comprises a first expression vector encoding a first protein of a protein complex and a further expression vector encoding a further protein of the protein complex. The further protein may be non-identical to the first protein. In some embodiments, a payload nucleic acid is or comprises a first expression vector encoding a first domain of a protein and a further expression vector encoding a further domain of the protein. In some embodiments, a payload nucleic acid is or comprises a first expression vector encoding a first segment of a protein and a further expression vector encoding a further segment of the protein. [123] In some embodiments, a payload nucleic acid expresses or is intended to express an expression product that is endogenous to the subject or system of interest in which the payload nucleic acid is administered. In some embodiments, a payload nucleic expresses or is intended to express a functional gene, or fragment thereof, to replace and/or supplement a gene that is otherwise not fully functional. [124] In some embodiments, a payload nucleic acid expresses or is intended to express an expression product that is useful in treating a neurological disease, disorder or condition. In some embodiments, a payload nucleic acid expresses or is intended to express an expression product that is useful in treating an inflammatory disease, disorder or condition. [125] In some embodiments, a neurological disease, disorder or condition is or comprises Alzheimer’s Disease. In some embodiments, a neurological disease, disorder or condition is or comprises Parkinson’s Disease. [126] In some embodiments, a payload nucleic acid expresses or is intended to express an expression product that is exogenous to the subject or system of interest in which the payload nucleic acid is administered. In some embodiments, a payload nucleic acid is or comprises a transgene. [127] In some embodiments, a payload nucleic acid encodes and/or expresses (or is the complement of a nucleic acid that encodes or expresses) an antibody, an antibody gene therapy system, and/or an antigen-binding molecule. [128] An antibody gene therapy system refers to a system in which nucleic acids encoding an antibody of interest is delivered to cells wherein said cells produce and secrete the encoded antibody. In some embodiments, a payload nucleic acid encodes and/or expresses (or is the complement of a nucleic acid that encodes or expresses) one or more components of an antibody gene therapy system. In some embodiments, an antibody gene therapy system is encoded by the same nucleic acid molecule or separate nucleic acid molecules. In some embodiments, an antibody gene therapy system is encoded by one or more DNA molecules. In some embodiments, an antibody gene therapy system is encoded by one or more plasmids. In some embodiments, an antibody gene therapy system is encoded by one or more expression vectors. In some embodiments, an antibody gene therapy system is encoded by one or more mRNA molecules. In some embodiments, an antibody gene therapy system is encoded by one or more minicircles. In some embodiments, an antibody gene therapy system is encoded by one or more dumbbell-shaped DNA minimal vectors. [129] An antigen-binding molecule refers to a molecule which is capable of binding to a target antigen. An antigen-binding molecule may be a monoclonal antibody, a polyclonal antibody, a monospecific antibody, a multispecific antibody (e.g., a bispecific antibody), or an antibody fragment (e.g., Fv, scFv, Fab, scFab, F(ab’)2, Fab2, diabody, triabody, scFv-Fc, minibody, single domain antibody (e.g., VhH), etc.), as long as it displays binding to the relevant target molecule(s). [130] In some embodiments, an antibody, or fragment thereof, or antigen-binding molecule is human, humanized, murine, camelid, chimeric, or from another suitable source. In some embodiments, an antibody, or fragment thereof, or antigen-binding molecule is humanized. Methods of humanizing antibodies may involve the fusing of variable domains of rodent origin to constant domains of human origin such that the resultant antibody retains the antigenic specificity of the rodent parented antibody, for example, as described in Morrison et al (1984) Proc. Natl. Acad. Sd. USA 81, 6851-6855. [131] Monoclonal antibodies (mAbs) refer to a homogenous population of antibodies that specifically bind a single epitope on an antigen. Suitable monoclonal antibodies to selected antigens may be prepared by known techniques, for example, those disclosed in Köhler, G.; Milstein, C. (1975) "Continuous cultures of fused cells secreting antibody of predefined specificity". Nature 256 (5517): 495; Siegel DL (2002). "Recombinant monoclonal antibody technology";. Schmitz U, Versmold A, Kaufmann P, Frank HG (2000) "Phage display: a molecular tool for the generation of antibodies--a review". Placenta.21 Suppl A: S106–12; Helen E. Chadd and Steven M. Chamow; “Therapeutic antibody expression technology,” Current Opinion in Biotechnology 12, no.2 (April 1, 2001): 188-194; McCafferty, J.; Griffiths, A.; Winter, G.; Chiswell, D. (1990) "Phage antibodies: filamentous phage displaying antibody variable domains" Nature 348 (6301): 552–554; "Monoclonal Antibodies: A manual of techniques "; H Zola (CRC Press, 1988); and "Monoclonal Hybridoma Antibodies: Techniques and Applications ", J G R Hurrell (CRC Press, 1982). Chimaeric antibodies are discussed by Neuberger et al (1988, 8th International Biotechnology Symposium Part 2, 792-799)). [132] Polyclonal antibodies (pAbs) refer to a heterologous population of antibodies that bind different epitopes on a single antigen. In some embodiments, polyclonal antibodies are monospecific. Suitable polyclonal antibodies can be prepared using methods known in the art. [133] In some embodiments, a payload nucleic acid encodes and/or expresses (or is the complement of a nucleic acid that encodes or expresses) a heavy chain or light chain of an antibody. In some embodiments, a payload nucleic acid encodes and/or expresses (or is the complement of a nucleic acid that encodes or expresses) a heavy chain of an antibody, and a further payload nucleic acid encodes and/or expresses (or is the complement of a nucleic acid that encodes or expresses) a light chain of an antibody, and when the at least two payloads are delivered in the same cell, cell type, or tissue an antibody is formed. [134] An antibody fragment refers to a fragment or shortened sequence of an antibody which retains binding to relevant target molecule(s). Antigenic specificity is conferred by variable domains and is independent of constant domains. Molecules that possess antigen- binding properties include, but are not limited to, Fab-like molecules (Better et al. (1988) Science 240, 1041); Fv molecules (Skerra et al. (1988) Science 240, 1038); single-chain Fv (ScFv) molecules where the VH and VL partner domains are linked via a flexible oligopeptide (Bird et al. (1988) Science 242, 423; Huston et al. (1988) Proc. Natl. Acad. Sd. USA 85, 5879) and single domain antibodies (dAbs) comprising isolated V domains (Ward et al. (1989) Nature 341, 544). A general review of the techniques involved in synthesizing antibody fragments which retain antigenic specificity can be found in Winter & Milstein (1991) Nature 349, 293- 299. [135] A single-chain variable fragment (scFv) refers to molecules wherein the heavy chain variable domain (VH) and light chain variable domain (VL) are covalently linked (e.g., by a peptide or a flexible oligopeptide). A single domain antibody (sdAb) refers to molecules comprising one, two, or more single monomeric variable antibody domains. A single chain antibody (scAb) refers to molecules comprising covalently linked VH and VL partner domains (e.g., by a peptide or a flexible oligopeptide). [136] A payload nucleic acid may encode and/or express (or is the complement of a nucleic acid that encodes or expresses) 3F8, 8H9, Abagovomab, Abciximab (ReoPro), Abituzumab, Abrezekimab, Abrilumab, Actoxumab, Adalimumab (Humira), Adecatumumab, Aducanumab, Afasevikumab, Afelimomab, Alacizumab pegol, Alemtuzumab (Lemtrada), Alirocumab (Praluent), Altumomab pentetate (Hybri-ceaker), Amatuximab, Amivantamab, Anatumomab mafenatox, Andecaliximab, Anetumab ravtansine, Anifrolumab, Ansuvimab (Ebanga), Anrukinzumab (= IMA-638), Apolizumab, Aprutumab ixadotin, Arcitumomab (CEA-Scan), Ascrinvacumab, Aselizumab, Atezolizumab (Tecentriq), Atidortoxumab, Atinumab, Atoltivimab, Atoltivimab/maftivimab/odesivimab (Inmazeb), Atorolimumab, Avelumab (Bavencio), Azintuxizumab vedotin, Balstilimab, Bamlanivimab, Bapineuzumab, Basiliximab (Simulect), Bavituximab, BCD-100, Bectumomab (LymphoScan), Begelomab, Belantamab mafodotin (Blenrep), Belimumab (Benlysta), Bemarituzumab, Benralizumab (Fasenra), Berlimatoxumab, Bermekimab (Xilonix), Bersanlimab, Bertilimumab, Besilesomab (Scintimun), Bevacizumab (Avastin), Bezlotoxumab (Zinplava), Biciromab (FibriScint), Bimagrumab, Bimekizumab, Birtamimab, Bivatuzumab, Bleselumab, Blinatumomab (Blincyto), Blontuvetmab (Blontress), Blosozumab, Bococizumab, Brazikumab, Brentuximab vedotin (Adcentris), Briakinumab, Brodalumab (Siliq), Brolucizumab (Beovu), Brontictuzumab, Burosumab (Crysvita), Cabiralizumab, Camidanlumab tesirine, Camrelizumab, Canakinumab (Ilaris), Cantuzumab mertansine, Cantuzumab ravtansine, Caplacizumab (Cablivi), Casirivimab, Capromab (Prostascint), Carlumab, Carotuximab, Catumaxomab (Removab), cBR96-doxorubicin immunoconjugate, Cedelizumab, Cemiplimab (Libtayo), Cergutuzumab amunaleukin, Certolizumab pegol (Cimzia), Cetrelimab, Cetuximab (Erbitux), Cibisatamab, Cirmtuzumab, Citatuzumab bogatox, Cixutumumab, Clazakizumab, Clenoliximab, Clivatuzumab tetraxetan (hPAM4-Cide), Codrituzumab, Cofetuzumab pelidotin, Coltuximab ravtansine, Conatumumab, Concizumab, Cosfroviximab (ZMapp), Crenezumab, Crizanlizumab (Adakveo), Crotedumab, CR6261, Cusatuzumab, Dacetuzumab, Daclizumab (Zenapax), Dalotuzumab, Dapirolizumab pegol, Daratumumab (Darzalex), Dectrekumab, Demcizumab, Denintuzumab mafodotin, Denosumab (Prolia), Depatuxizumab mafodotin, Derlotuximab biotin, Detumomab, Dezamizumab, Dinutuximab (Unituxin), Dinutuximab beta (Qarziba), Diridavumab, Domagrozumab, Dorlimomab aritox, Dostarlimab, Drozitumab, DS-8201, Duligotuzumab, Dupilumab (Dupixent), Durvalumab (Imfinzi), Dusigitumab, Duvortuxizumab, Ecromeximab, Eculizumab (Soliris), Edobacomab, Edrecolomab (Panorex), Efalizumab (Raptiva), Efungumab (Mycograb), Eldelumab, Elezanumab, Elgemtumab, Elotuzumab (Empliciti), Elsilimomab, Emactuzumab, Emapalumab (Gamifant), Emibetuzumab, Emicizumab (Hemlibra), Enapotamab vedotin, Enavatuzumab, Enfortumab vedotin (Padcev), Enlimomab pegol, Enoblituzumab, Enokizumab, Enoticumab, Ensituximab, Epcoritamab, Epitumomab cituxetan, Epratuzumab, Eptinezumab (Vyepti), Erenumab (Aimovig), Erlizumab, Ertumaxomab (Rexomun), Etaracizumab (Abegrin), Etesevimab, Etigilimab, Etrolizumab, Evinacumab (Evkeeza), Evolocumab (Repatha), Exbivirumab, Fanolesomab (NeutroSpec), Faralimomab, Faricimab, Farletuzumab, Fasinumab, FBTA05 (Lymphomun), Felvizumab, Fezakinumab, Fibatuzumab, Ficlatuzumab, Figitumumab, Firivumab, Flanvotumab, Fletikumab, Flotetuzumab, Fontolizumab (HuZAF), Foralumab, Foravirumab, Fremanezumab (Ajovy), Fresolimumab, Frovocimab, Frunevetmab, Fulranumab, Futuximab, Galcanezumab (Emgality), Galiximab, Gancotamab, Ganitumab, Gantenerumab, Gatipotuzumab, Gavilimomab, Gedivumab, Gemtuzumab ozogamicin (Mylotarg), Gevokizumab, Gilvetmab, Gimsilumab, Girentuximab (Rencarex), Glembatumumab vedotin, Golimumab (Simponi), Gomiliximab, Gosuranemab, Guselkumab (Tremfya), Ianalumab, Ibalizumab (Trogarzo), IBI308, Ibritumomab tiuxetan (Zevalin), Icrucumab, Idarucizumab (Praxbind), Ifabotuzumab, Igovomab (Indimacis-125), Iladatuzumab vedotin, IMAB362, Imalumab, Imaprelimab, Imciromab (Myoscint), Imdevimab, Imgatuzumab, Inclacumab, Indatuximab ravtansine, Indusatumab vedotin, Inebilizumab (Uplizna), Infliximab (Remicade), Intetumumab, Inolimomab, Inotuzumab ozogamicin (Besponsa), Ipilimumab (Yervoy), Iomab-B, Iratumumab, Isatuximab (Sarclisa), Iscalimab, Istiratumab, Itolizumab (Alzumab), Ixekizumab (Taltz), Keliximab, Labetuzumab (CEA-Cide), Lacnotuzumab, Ladiratuzumab vedotin, Lampalizumab, Lanadelumab (Takhzyro), Landogrozumab, Laprituximab emtansine, Larcaviximab, Lebrikizumab, Lemalesomab, Lendalizumab, Lenvervimab, Lenzilumab, Lerdelimumab, Leronlimab, Lesofavumab, Letolizumab, Lexatumumab, Libivirumab, Lifastuzumab vedotin, Ligelizumab, Loncastuximab tesirine, Losatuxizumab vedotin, Lilotomab satetraxetan, Lintuzumab, Lirilumab, Lodelcizumab, Lokivetmab (Cytopoint), Lorvotuzumab mertansine, Lucatumumab, Lulizumab pegol, Lumiliximab, Lumretuzumab, Lupartumab, Lupartumab amadotin, Lutikizumab, Maftivimab, Mapatumumab, Margetuximab (Margenza), Marstacimab, Maslimomab, Mavrilimumab, Matuzumab, Mepolizumab (Bosatria), Metelimumab, Milatuzumab, Minretumomab, Mirikizumab, Mirvetuximab soravtansine, Mitumomab, Modotuximab, Mogamulizumab (Poteligeo), Monalizumab, Morolimumab, Mosunetuzumab, Motavizumab (Numax), Moxetumomab pasudotox (Lumoxiti), Muromonab-CD3 (Orthoclone OKT3), Nacolomab tafenatox, Namilumab, Naptumomab estafenatox, Naratuximab emtansine, Narnatumab, Narsoplimab, Natalizumab (Tysabri), Navicixizumab, Navivumab, Naxitamab (Danyelza), Nebacumab, Necitumumab (Portrazza), Nemolizumab, NEOD001, Nerelimomab, Nesvacumab, Netakimab (Efleira), Nimotuzumab (BioMab-EGFR, Theracim, Theraloc), Nirsevimab, Nivolumab (Opdivo), Nofetumomab merpentan (Verluma), Obiltoxaximab (Anthim), Obinutuzumab (Gazyva), Ocaratuzumab, Ocrelizumab (Ocrevus), Odesivimab, Odulimomab, Ofatumumab (Arzerra, Kesimpta), Olaratumab (Lartruvo), Oleclumab, Olendalizumab, Olokizumab, Omalizumab (Xolair), Omburtamab, OMS721, Onartuzumab, Ontuxizumab, Onvatilimab, Opicinumab, Oportuzumab monatox (Vicinium), Oregovomab (OvaRex), Orticumab, Otelixizumab, Otilimab, Otlertuzumab, Oxelumab, Ozanezumab, Ozoralizumab, Pagibaximab, Palivizumab (Synagis, Abbosynagis), Pamrevlumab, Panitumumab (Vectibix), Pankomab, Panobacumab, Parsatuzumab, Pascolizumab, Pasotuxizumab, Pateclizumab, Patritumab, PDR001, Pembrolizumab (Keytruda), Pemtumomab (Theragyn), Perakizumab, Pertuzumab (Perjeta), Pexelizumab, Pidilizumab, Pinatuzumab vedotin, Pintumomab, Placulumab, Prezalumab, Plozalizumab, Pogalizumab, Polatuzumab vedotin (Polivy), Ponezumab, Porgaviximab, Prasinezumab, Prezalizumab, Priliximab, Pritoxaximab, Pritumumab, PRO 140, Quilizumab, Racotumomab (Vaxira), Radretumab, Rafivirumab, Ralpancizumab, Ramucirumab (Cyramza), Ranevetmab, Ranibizumab (Lucentis), Raxibacumab, Ravagalimab, Ravulizumab (Ultomiris), Refanezumab, Regavirumab, Regdanvimab, REGN-EB3, Relatlimab, Remtolumab, Reslizumab (Cinqair), Retifanlimab, Rilotumumab, Rinucumab, Risankizumab (Skyrizi), Rituximab (MabThera, Rituxan), Rivabazumab pegol, Robatumumab, Rmab (RabiShield), Roledumab, Romilkimab, Romosozumab (Evenity), Rontalizumab, Rosmantuzumab, Rovalpituzumab tesirine, Rovelizumab (LeukArrest), Rozanolixizumab, Ruplizumab (Antova), SA237, Sacituzumab govitecan (Trodelvy), Samalizumab, Samrotamab vedotin, Sarilumab (Kevzara), Satralizumab (Enspryng), Satumomab pendetide, Secukinumab (Cosentyx), Selicrelumab, Seribantumab, Setoxaximab, Setrusumab, Sevirumab, Sibrotuzumab, SGN-CD19A, SHP647, Sifalimumab, Siltuximab (Sylvant), Simtuzumab, Siplizumab, Sirtratumab vedotin, Sirukumab, Sofituzumab vedotin, Solanezumab, Solitomab, Sonepcizumab, Sontuzumab, Spartalizumab, Stamulumab, Sulesomab (LeukoScan), Suptavumab, Sutimlimab, Suvizumab, Suvratoxumab, Tabalumab, Tacatuzumab tetraxetan (AFP-Cide), Tadocizumab, Tafasitamab (Monjuvi), Talacotuzumab, Talizumab, Talquetamab, Tamtuvetmab (Tactress), Tanezumab, Taplitumomab paptox, Tarextumab, Tavolimab, Teclistamab, Tefibazumab (Aurexis), Telimomab aritox, Telisotuzumab, Telisotuzumab vedotin, Tenatumomab, Teneliximab, Teplizumab, Tepoditamab, Teprotumumab (Tepezza), Tesidolumab, Tetulomab, Tezepelumab, TGN1412, Tibulizumab, Tildrakizumab (Ilumya), Tigatuzumab, Timigutuzumab, Timolumab, Tiragolumab, Tiragotumab, Tislelizumab, Tisotumab vedotin, TNX-650, Tocilizumab (Actemra, RoActemra), Tomuzotuximab, Toralizumab, Toripalimab (Tuoyi), Tosatoxumab, Tositumomab (Bexxar), Tovetumab, Tralokinumab, Trastuzumab (Herceptin), [fam]-trastuzumab deruxtecan (Enhertu), Trastuzumab duocarmazine (Kadcyla), Trastuzumab emtansine (Kadcyla), TRBS07 (Ektomab), Tregalizumab, Tremelimumab, Trevogrumab, Tucotuzumab celmoleukin, Tuvirumab, Ublituximab, Ulocuplumab, Urelumab, Urtoxazumab, Ustekinumab (Stelara), Utomilumab, Vadastuximab talirine, Vanalimab, Vandortuzumab vedotin, Vantictumab, Vanucizumab, Vapaliximab, Varisacumab, Varlilumab, Vatelizumab, Vedolizumab (Entyvio), Veltuzumab, Vepalimomab, Vesencumab, Visilizumab (Nuvion), Vobarilizumab, Volociximab, Vonlerolizumab, Vopratelimab, Vorsetuzumab mafodotin, Votumumab (HumaSPECT), Vunakizumab, Xentuzumab, XMAB-5574, Zalutumumab, Zanolimumab, Zatuximab, Zenocutuzumab, Ziralimumab, Zolbetuximab (IMAB362, Claudiximab), or Zolimomab aritox. An antigen-binding molecule may be a derivative of any of the abovementioned antibodies. [137] In some embodiments, a payload nucleic acid encodes and/or expresses (or is the complement of a nucleic acid that encodes or expresses) one or more components of a gene editing system. [138] CRISPR is an abbreviation of Clustered Regularly Interspaced Short Palindromic Repeats. CRISPR comprises segments of DNA containing short, repetitive base sequences in a palindromic repeat (wherein the sequence of nucleotides is the same in both directions). Each repetition is followed by short segments of spacer DNA from previous integration of foreign DNA from a virus or plasmid. Small clusters of Cas (CRISPR-associated) genes are located next to CRISPR sequences. RNA harboring the spacer sequence helps Cas (CRISPR-associated) proteins recognize and cut foreign pathogenic DNA. Other RNA- guided Cas proteins cut foreign RNA. An embodiment of the CRISPR/Cas system, CRISPR/Cas9, has been modified to edit genomes. By delivering the Cas9 nuclease and a synthetic guide RNA (gRNA) into a cell, the cell's genome can be cut at a desired location, allowing existing genes to be removed and/or new ones added. CRISPR/Cas systems fall into two classes. Class 1 systems use a complex of multiple Cas proteins to degrade foreign nucleic acids. Class 2 systems use a single large Cas protein for the same purpose. Class 1 is divided into types I, III, and IV; class 2 is divided into types II, V, and VI. CRISPR genome editing uses a type II CRISPR system. [139] In some embodiments, a payload nucleic acid encodes and/or expresses (or is the complement of a nucleic acid that encodes or expresses) one or more components of a CRISPR/Cas gene editing system. In some embodiments, a payload nucleic acid recognizes a particular target sequence. In some embodiments, a payload nucleic acid is or comprises a guide RNA (gRNA). In some embodiments, a guide RNA comprises a CRISPR RNA (crRNA) and a trans-activating CRISPR RNA (tracrRNA). crRNA may comprise a sequence that binds and/or identifies a host DNA sequence and a region that binds to tracrRNA to form an active complex. In some embodiments, a gRNA combines both crRNA and tracrRNA thereby encoding an active complex. In some embodiments, a gRNA may comprises multiple crRNAs and/or multiple tracrRNAs. In some embodiments, a gRNA is designed to bind and/or otherwise identify a sequence or gene of interest. In some embodiments, a gRNA targets a sequence or gene of interest for cleavage. In some embodiments, a template DNA sequence is included. In some embodiments, a template DNA sequence is utilized in either non-homologous end joining (NHEJ) or homology directed repair (HDR). [140] In some embodiments, a payload nucleic acid encodes and/or expresses (or is the complement of a nucleic acid that encodes or expresses) a nuclease. In some embodiments, a payload nucleic acid encodes and/or expresses (or is the complement of a nucleic acid that encodes or expresses) a Cas nuclease. One of ordinary skill in the art will appreciate that Cas nuclease may refer to any Cas protein (e.g., Cas 9, Cas12, etc.). One of ordinary skill in the art will appreciate that a nuclease may refer to any protein that functions to modify nucleic acid (e.g., single strand nicking, double strand breaking, DNA binding, etc.). A nuclease recognizes a DNA site and allows for site-specific DNA editing. In some embodiments, a nuclease is modified. In some embodiments, a nuclease is fused to a reverse transcriptase. In some embodiments, a nuclease is catalytically inactive. In some embodiments, a nuclease is fused to a transcription factor. A modified nuclease may be useful, for example, in a prime editing system or in systems to regulate transcription. [141] In some embodiments, a payload nucleic acid encodes and/or expresses (or is the complement of a nucleic acid that encodes or expresses) at least a gRNA and a nuclease. In some embodiments, a payload nucleic acid encodes and/or expresses (or is the complement of a nucleic acid that encodes or expresses) at least a gRNA and a nuclease on a plasmid. In some embodiments, a gRNA and a nuclease are encoded on a single plasmid. In some embodiments, a gRNA and a nuclease are encoded on separate plasmids. [142] In some embodiments, a payload nucleic acid is or comprises a DNA repair template. In some embodiments, a DNA repair template is or comprises a linear double-stranded DNA. In some embodiments, a DNA repair template is a plasmid. In some embodiments, a DNA repair template is present on the same nucleic acid which encodes a gRNA and/or nuclease. In some embodiments, a DNA repair template is present on a separate nucleic acid from the nucleic acid which encodes a gRNA and/or a nuclease. [143] CRISPR/Cas9 and related systems (e.g., CRISPR/Cpf1, CRISPR/C2c1, CRISPR/C2c2 and CRISPR/C2c3) are reviewed, for example, in Nakade et al., Bioengineered (2017) 8(3):265-273, which is hereby incorporated by reference in its entirety. These systems comprise an endonuclease (e.g., Cas9, Cpf1, etc.) and a single- guide RNA (sgRNA) molecule. A sgRNA can be engineered to target endonuclease activity to nucleic acid sequences of interest. [144] In some embodiments, a payload nucleic acid encodes and/or expresses (or is the complement of a nucleic acid that encodes or expresses) one or more components of a gene editing system other than a CRISPR/Cas gene editing system (e.g., zinc finger nucleases (ZFNs) or transcription activator-like effector nucleases (TALENs)). [145] In some embodiments, a gene editing system specifically targets a miRNA. In some embodiments, a gene editing system specifically targets miR-125b. [146] In some embodiments, a gene editing system employs targeted gene editing using a site-specific nuclease (SSN). Gene editing with SSNs is reviewed, for example, in Eid and Mahfouz, Exp Mol Med.2016 Oct; 48(10): e265, which is hereby incorporated by reference in its entirety. Enzymes capable of creating site-specific double strand breaks (DSBs) may be engineered to introduce DSBs to target nucleic acid sequence(s) of interest. DSBs may be repaired by error-prone non-homologous end-joining (NHEJ), in which the two ends of the break are rejoined, often with insertion or deletion of nucleotides. Alternatively, DSBs may be repaired by homology-directed repair (HDR), in which a DNA template with ends homologous to the break site is supplied and introduced at the site of the DSB. [147] SSNs capable of being engineered to generate target nucleic acid sequence-specific DSBs include ZFNs, TALENs and clustered regularly interspaced palindromic repeats/CRISPR-associated-9 (CRISPR/Cas9) systems. [148] ZFN systems are reviewed, for example, in Umov et al., Nat Rev Genet. (2010) 11(9):636-46, which is hereby incorporated by reference in its entirety. ZFNs comprise a programmable Zinc Finger DNA-binding domain and a DNA-cleaving domain (e.g. a FokI endonuclease domain). The DNA-binding domain may be identified by screening a Zinc Finger array capable of binding to the target nucleic acid sequence. [149] ZFNs work in pairs as the endonuclease (e.g., FokI) functions as a dimer. A ZFN system comprises two monomers with unique DNA recognition sites in the target genome with proper orientation (i.e. on opposite DNA strands) and spacing to allow the endonuclease to function. [150] In some embodiments, a payload nucleic acid encodes and/or expresses (or is the complement of a nucleic acid that encodes or expresses) one or more components of a ZFN gene editing system. In some embodiments, a ZFN gene editing system comprises a ZFN pair having two polypeptide monomers. In some embodiments, a ZFN gene editing system is encoded by the same nucleic acid molecule or separate nucleic acid molecules. In some embodiments, a ZFN gene editing system is encoded by one or more DNA molecules. In some embodiments, a ZFN gene editing system is encoded by one or more plasmids. In some embodiments, a ZFN gene editing system is encoded by one or more expression vectors. In some embodiments, a ZFN gene editing system is encoded by one or more mRNA molecules. In some embodiments, a ZFN gene editing system is encoded by one or more minicircles. In some embodiments, a ZFN gene editing system is encoded by one or more dumbbell-shaped DNA minimal vectors. [151] In some embodiments, two payload nucleic acids comprise a first nucleic acid molecule that encodes first monomer of a ZFN pair and a further nucleic acid molecule that encodes a second monomer of a ZFN pair. The nucleic acids may comprise an expression cassette such that the ZFN monomers are expressed within a target cell. The expressed ZFN monomers may bind to their respective DNA recognition sites and allow dimerization of endonuclease. The endonuclease may function to introduce a DSB into the DNA. [152] TALEN systems are reviewed, for example, in Mahfouz et al., Plant Biotechnol J. (2014) 12(8):1006-14, which is hereby incorporated by reference in its entirety. TALENs comprise a programmable DNA-binding TALE domain and a DNA-cleaving domain (e.g., a FokI endonuclease domain). TALEs comprise repeat domains consisting of repeats of 33-39 amino acids, which are identical except for two residues at positions 12 and 13 of each repeat which are repeat variable di-residues (RVDs). Each RVD determines binding of the repeat to a nucleotide in the target DNA sequence according to the following relationship: “HD” binds to C, “NI” binds to A, “NG” binds to T and “NN” or “NK” binds to G (see, for example, Moscou and Bogdanove, Science (2009) 326(5959):1501 which is hereby incorporated by reference in its entirety). [153] TALENs work in pairs as the endonuclease (e.g., FokI) functions as a dimer. A TALEN system comprises two monomers with unique DNA recognition sites in the target genome with proper orientation (i.e., on opposite DNA strands) and spacing to allow the endonuclease to function. [154] In some embodiments, a payload nucleic acid encodes and/or expresses (or is the complement of a nucleic acid that encodes or expresses) one or more components of a TALEN gene editing system. In some embodiments, a TALEN gene editing system comprises a TALEN pair having two polypeptide monomers. In some embodiments, a TALEN gene editing system is encoded by the same nucleic acid molecule or separate nucleic acid molecules. In some embodiments, a TALEN gene editing system is encoded by one or more DNA molecules. In some embodiments, a TALEN gene editing system is encoded by one or more plasmids. In some embodiments, a TALEN gene editing system is encoded by one or more expression vectors. In some embodiments, a TALEN gene editing system is encoded by one or more mRNA molecules. In some embodiments, a TALEN gene editing system is encoded by one or more minicircles. In some embodiments, a TALEN gene editing system is encoded by one or more dumbbell-shaped DNA minimal vectors. [155] In some embodiments, two payload nucleic acids comprise a first nucleic acid molecule that encodes first monomer of a TALEN pair and a further nucleic acid molecule that encodes a second monomer of a TALEN pair. The nucleic acids may comprise an expression cassette such that the TALEN monomers are expressed within a target cell. The expressed ZFN monomers may bind to their respective DNA recognition sites and allow dimerization of endonuclease. The endonuclease may function to introduce a DSB into the DNA. [156] In some embodiments, a payload nucleic acid encodes and/or expresses (or is the complement of a nucleic acid that encodes or expresses) a vaccine. In some embodiments, a payload nucleic acid encodes and/or expresses (or is the complement of a nucleic acid that encodes or expresses) an epitope sequence. [157] In some embodiments, a payload nucleic acid encodes and/or expresses (or is the complement of a nucleic acid that encodes or expresses) a vaccine to cancer. Cancer vaccines involve displaying a tumor-specific antigen or a tumor-associated antigen to a subject’s immune system such that the immune system is able to more effectively recognize cancerous cells. Cancer vaccines are reviewed, for example, in Vergati, Matteo, et al. "Strategies for cancer vaccine development." Journal of Biomedicine and Biotechnology (2010), which is hereby incorporated by reference. One of ordinary skill in the art will be able to select a tumor-specific antigen or tumor-associated antigen for any particular cancer type using methods known in the art. In some embodiments, a payload nucleic acid encodes and/or expresses (or is the complement of a nucleic acid that encodes or expresses) a tumor- specific antigen. In some embodiments, a payload nucleic acid encodes and/or expresses (or is the complement of a nucleic acid that encodes or expresses) a tumor-associated antigen. [158] In some embodiments, a cancer vaccine is encoded by one or more DNA molecules. In some embodiments, a cancer vaccine is encoded by one or more plasmids. In some embodiments, a cancer vaccine is encoded by one or more expression vectors. In some embodiments, a cancer vaccine is encoded by one or more mRNA molecules. In some embodiments, a cancer vaccine is encoded by one or more minicircles. In some embodiments, a cancer vaccine is encoded by one or more dumbbell-shaped DNA minimal vectors. [159] In some embodiments, a payload nucleic acid encodes and/or expresses (or is the complement of a nucleic acid that encodes or expresses) a vaccine to a pathogen. In some embodiments, a payload nucleic acid encodes and/or expresses (or is the complement of a nucleic acid that encodes or expresses) a vaccine to a bacteria. In some embodiments, a payload nucleic acid encodes and/or expresses (or is the complement of a nucleic acid that encodes or expresses) a vaccine to a virus. Pathogen vaccines involve displaying a pathogen-specific antigen to a subject’s immune system such that the immune system is able to more effectively recognize foreign pathogens. One of ordinary skill in the art will be able to select a pathogen-specific antigen for any particular pathogen using methods known in the art. [160] In some embodiments, a pathogen vaccine is encoded by one or more DNA molecules. In some embodiments, a pathogen vaccine is encoded by one or more plasmids. In some embodiments, a pathogen vaccine is encoded by one or more expression vectors. In some embodiments, a pathogen vaccine is encoded by one or more mRNA molecules. In some embodiments, a pathogen vaccine is encoded by one or more minicircles. In some embodiments, a pathogen vaccine is encoded by one or more dumbbell-shaped DNA minimal vectors. [161] In some embodiments, a payload nucleic acid is diagnostic. In some embodiments, a payload nucleic acid encodes and/or expresses (or is the complement of a nucleic acid that encodes or expresses) a reporter gene and/or a molecule that is detectable. Promoting Oligonucleotide [162] As described herein, a promoting oligonucleotide is a nucleic acid whose presence is associated with (a) increased level and/or activity of an expression product of a payload; and/or (b) decreased inflammatory and/or otherwise undesirable effect or response (e.g., immune effect or response) associated with administration or delivery of a payload nucleic acid. [163] In some embodiments, a promoting oligonucleotide is or comprises double-stranded DNA (dsDNA). In some embodiments a dsDNA promoting oligonucleotide is or comprises two DNA strands. In some embodiments, a dsDNA promoting oligonucleotide has a length within a range of 5-200 base pairs. In some embodiments, a dsDNA promoting oligonucleotide has a length of 5, 10, 15, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 120, 140, 160, 180, or 200 base pairs. In some embodiments, a dsDNA promoting oligonucleotide has a length of at least 5 base pairs. In some embodiments, a dsDNA promoting oligonucleotide has a length of at most 40 base pairs. [164] In some embodiments, a promoting oligonucleotide is or comprises single-stranded DNA (ssDNA). An ssDNA promoting oligonucleotide may or may not comprise self- complementary regions. In some embodiments, an ssDNA promoting oligonucleotide comprises one or more stem-loop structures. In some embodiments, an ssDNA promoting oligonucleotide comprises two stem-loop structures (e.g., a ribbon shaped promoting oligonucleotide). In some embodiments, an ssDNA promoting oligonucleotide has a length within a range of 5-100 nucleotides. In some embodiments, an ssDNA promoting oligonucleotide has a length of 5, 10, 15, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 120, 140, 160, 180, or 200 nucleotides. In some embodiments, an ssDNA promoting oligonucleotide has a length of at least 5 nucleotides. In some embodiments, an ssDNA promoting oligonucleotide has a length of at most 40 nucleotides. [165] In some embodiments, a promoting oligonucleotide is or comprises a single RNA strand. An RNA promoting oligonucleotide may or may not comprise self-complementary regions. In some embodiments, an RNA promoting oligonucleotide has a length within a range of 5-100 nucleotides. In some embodiments, an RNA promoting oligonucleotide has a length of 5, 10, 15, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 120, 140, 160, 180, or 200 nucleotides. In some embodiments, an RNA promoting oligonucleotide has a length of at least 5 nucleotides. In some embodiments, an RNA promoting oligonucleotide has a length of at most 40 nucleotides. [166] In some embodiments, a promoting oligonucleotide comprises chemically modified nucleic acid. Chemical modifications may relate to, for example, a nucleotide, a sugar, a base, or a bond of or within a promoting oligonucleotide. In some embodiments, a promoting oligonucleotide comprises at least one phosphorothioate-modified bond. In some embodiments, every nucleotide bond of a promoting oligonucleotide is a phosphorothioate- modified bond. In some embodiments, at most 50% of the nucleotide bonds of the promoting oligonucleotide are phosphorothioate-bonds. In some embodiments, the nucleotide bonds that are phosphorothioate-bonds of the promoting oligonucleotide are at the 5’ and 3’ ends of the nucleic acid sequence. [167] In some embodiments, phosphorothioate-modified bonds are incorporated into a promoting oligonucleotide to control the oligonucleotide’s in vivo half-life (e.g., rate of degradation in a cell, tissue, organism, etc.). In some embodiments, the ratio of phosphorothioate-modified bonds to unmodified bonds in a promoting oligonucleotide is used to control the in vivo half-life. By modifying a promoting oligonucleotide’s in vivo half-life, the duration of the oligonucleotide’s effects may be controlled. In some embodiments, a promoting oligonucleotide’s in vivo half-life is decreased. In some embodiments, a promoting oligonucleotide’s in vivo half-life is decreased to minimize constitutive inhibition (e.g., of NF-κB). In some embodiments, a promoting oligonucleotide’s in vivo half-life is increased. In some embodiments, a promoting oligonucleotide’s in vivo half-life is increased to lessen the quantity of oligonucleotide that is required to achieve a biologic effect. [168] In some embodiments, a promoting oligonucleotide comprises one or more spacer molecules. In some embodiments, a spacer molecule comprises a linker used to cap the ends of dsDNA and DNA duplexes, such as, for example, hexaethylene glycol. [169] In many of the embodiments of the present disclosure, a promoting oligonucleotide does not encode for an expression product. The present disclosure surprisingly demonstrates that administration of a promoting oligonucleotide can avoid and/or limit one or more challenges associated with nucleic acid delivery (e.g., a payload nucleic acid). [170] In some embodiments, a promoting oligonucleotide increases the amount of nucleic acid loaded into a delivery vehicle, especially when the promoting oligonucleotide is co- loaded with a payload nucleic acid in an RBCEV. [171] In some embodiments, a promoting oligonucleotide can increase the level, expression or activity of a delivered nucleic acid (e.g., or of a product it encodes). In some embodiments, a promoting oligonucleotide increases the number of copies of payload nucleic acid delivered to a system (e.g., a cell, tissue, or organism). In some embodiments, a promoting oligonucleotide increases the number of cells that receive delivery of a payload nucleic acid. In some embodiments, a promoting oligonucleotide increases the amount of expression product expressed per copy of payload nucleic acid. In some embodiments, a promoting oligonucleotide decreases the amount of payload nucleic acid (e.g., or of a product it encodes) degraded upon delivery to a system. [172] In some embodiments, a promoting oligonucleotide can decrease inflammatory and/or otherwise undesirable effect or response (e.g., immune effect or response) associated with administration or delivery of a payload nucleic acid. In some embodiments, administration of a promoting oligonucleotide decreases expression and/or release of indicative marker(s) of inflammatory and/or otherwise undesirable effect or response (e.g., immune effect or response) associated with administration or delivery of a payload nucleic acid. In some embodiments, administration of a promoting oligonucleotide decreases cytokine expression and/or release associated with administration or delivery of a payload nucleic acid. In some embodiments, administration of a promoting oligonucleotide decreases type I IFN (e.g., IFNa, IFNb, etc.), IL6, CXCL10, and/or CCL2 expression and/or release associated with administration or delivery of a payload nucleic acid. [173] In some embodiments, a promoting oligonucleotide interacts with a factor endogenous to a cell in which the promoting oligonucleotide has been delivered in order to effect decreased inflammatory and/or otherwise undesirable effect or response (e.g., immune effect or response) associated with administration or delivery of a payload nucleic acid. In some embodiments, a promoting oligonucleotide interacts with a factor endogenous to a cell that typically functions to bind nucleic acid. In some embodiments, a promoting oligonucleotide interacts with a transcription factor. In some embodiments, a promoting oligonucleotide interacts with an RNA-binding protein. In some embodiments, a promoting oligonucleotide interacts with any factor that can be bound by an aptamer. [174] In some embodiments, a promoting oligonucleotide prevents and/or inhibits an endogenous factor of a cell from interacting with a payload nucleic acid. This prevention and/or inhibition of interaction between an endogenous factor of a cell and a payload nucleic acid by a promoting oligonucleotide may be through direct means (e.g., a promoting oligonucleotide interacting with a factor such that it is unable to interact with a payload nucleic acid) or through indirect means (e.g., a promoting oligonucleotide interacting with a factor that regulates the function or activity of a further factor which might otherwise interact with a payload nucleic acid). [175] In some embodiments, a promoting oligonucleotide acts as a decoy, lure, trap, bait, mimic, squelch, and/or sink to a factor endogenous to a cell in which the promoting oligonucleotide has been delivered (i.e., acts to absorb and/or neutralize the biologic effects of an endogenous factor such that its endogenous functions are lessened). For example, a promoting oligonucleotide may be or comprise a decoy to a transcription factor; such a decoy could interact with a target transcription factor upon delivery to a cell and decrease the transcription factor’s binding to target DNA sequences within the cell’s nucleus. In some embodiments, a promoting oligonucleotide is or comprises a decoy to an effector of a nucleic acid sensing pathway. In some embodiments, a promoting oligonucleotide is or comprises a decoy to an effector of the cGAS-STING signaling axis. In some embodiments, a promoting oligonucleotide is or comprises a decoy to an effector of the TLR9 signaling axis. In some embodiments, a promoting oligonucleotide is or comprises a decoy to an effector of an inflammatory and/or innate immune pathway. In some embodiments, a promoting oligonucleotide is or comprises an NF-κB decoy. In some embodiments, a promoting oligonucleotide is or comprises a decoy to DNA-dependent protein kinase (DNA- PK) and/or poly (ADP-ribose) polymerase (PARP). In some embodiments, a promoting oligonucleotide is or comprises a RIG-I decoy. IV. Compositions and Methods of EV Loading [176] As described herein, loading of an EV (e.g., an RBCEV) with a cargo nucleic acid refers to associating the EV and the cargo nucleic acid in stable or semi-stable form such that the EV is useful as a carrier of the cargo nucleic acid (e.g., allowing its delivery to cells). In some embodiments, cargo nucleic acids are loaded such that they are present in the lumen of the EV. In some embodiments, cargo nucleic acids are attached to, adhered to, inserted through, or complexed with the external surface (e.g., the membrane) of the EV. In some embodiments, cargo nucleic acids are loaded such that there are nucleic acids present in the lumen of the EV and there are nucleic acids attached to, adhered to, inserted through, or complexed with the external surface (e.g., the membrane) of the EV. [177] In some embodiments, at least one copy of a single cargo nucleic acid is loaded into EVs. In some embodiments, at least one copy each of two different cargo nucleic acids are loaded into EVs. In some embodiments, EVs are loaded with a first cargo nucleic acid, followed by loading of a second cargo nucleic acid. In some embodiments, EVs are loaded first with a payload nucleic acid followed by loading of a promoting oligonucleotide. In some embodiments, EVs are loaded first with a promoting oligonucleotide followed by loading of a payload nucleic acid. In some embodiments, EVs are loaded with two cargo nucleic acids simultaneously. In some embodiments, EVs are loaded simultaneously with a promoting oligonucleotide and a payload nucleic acid. [178] In some embodiments, methods of EV loading comprise contacting cargo nucleic acid with transfection reagent. In some embodiments, cargo nucleic acid and transfection reagent are brought together under suitable conditions and for suitable time to allow for EV loading to occur. In some embodiments, transfection reagents comprise cationic reagents such as cationic lipid reagents. Transfection reagents may be Lipofectamine ^TM 3000 ^TM (ThermoFisher), Turbofect ^TM (ThermoFisher), Lipofectamine ^TM MessengerMAX ^TM (ThermoFisher), Exofect ^TM (System Biosciences), Linear Polyethylenimine Hydrochlorides (e.g., having an average molecular weight of 25,000 Da or 40,000Da, such as PEIMax ^TM (Polysciences, Inc.) and jetPEI® (Polyplus transfection)), polybrene or protamine sulfate (see, for example, Delville et al. "A nontoxic transduction enhancer enables highly efficient lentiviral transduction of primary murine T cells and hematopoietic stem cells." Molecular Therapy-Methods & Clinical Development 10 (2018)). [179] In some embodiments, loading of cargo nucleic acids into EVs does not comprise viral delivery methods. In some embodiments, loading of cargo nucleic acids into EVs does not comprise a viral vector (e.g., an adenoviral vector, adeno-associated vector, lentiviral vector, retroviral vector, etc.). Preparing Cargo Nucleic Acids for Loading [180] In some embodiments, methods of EV loading comprise a step of preparing the cargo nucleic acid to be loaded. In some embodiments, the preparation step comprises contacting the nucleic acid to be loaded into EVs with transfection reagent under conditions suitable for the formation of a complex between the transfection reagent and the nucleic acid. The nucleic acid and transfection reagent may form a complex (e.g., DNA:PEIMax complex). In some embodiments, the preparation step comprises concentration or dilution of the nucleic acid. In some embodiments, the preparation step comprises addition of buffers or other reagents or media (e.g., Opti-MEM reduced serum media (Gibco)). In some embodiments, the nucleic acid and transfection reagent are contacted for at least 1 minute, at least 2 minutes, at least 3 minutes, at least 4 minutes, at least 5 minutes, at least 6 minutes, at least 7 minutes, at least 8 minutes, at least 9 minutes, at least 10 minutes, at least 11 minutes, at least 12 minutes, at least 13 minutes, at least 14 minutes, at least 15 minutes, at least 16 minutes, at least 17 minutes, at least 18 minutes, at least 19 minutes, at least 20 minutes, or more than 20 minutes. In some embodiments, the preparation step comprises combining a nucleic acid:transfection reagent complex with a further nucleic acid:transfection reagent complex wherein the nucleic acids are non-identical. [181] In some embodiments, nucleic acid:transfection reagent complexes contain identical nucleic acids. In some embodiments, nucleic acid:transfection reagent complexes contain non-identical nucleic acids in particular ratios. In some embodiments, two non-identical nucleic acid:transfection reagent complexes are combined. The transfection reagent of multiple complexes may or may not be identical. Non-identical nucleic acids may be present in complexes at equimolar amounts (i.e., at an equimolar ratio). Non-identical nucleic acids may not be present in complexes at equimolar amounts (i.e., at an equimolar ratio). The ratio may refer to the amount of a first nucleic acid in relation a further nucleic acid present in a mixture, wherein the first nucleic acid and further nucleic acid are to be contacted with EVs simultaneously. The ratio may refer to the amount of a first nucleic acid in relation a further nucleic acid present in a mixture, wherein the first nucleic acid and further nucleic acid are to be contacted with EVs in separate steps. [182] The first nucleic acid to be loaded and the further nucleic acid to be loaded may be present at a ratio of about 400:1, 300:1, 250:1, 200:1, 150:1, 100:1, 75:1, 50:1, 25:1, 20:1, 15:1, 10:1, 9:1, 8:1, 7:1, 6:1, 5:1, 4:1, 3:1, 2:1, 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:15, 1:20, 1:25, 1:50, 1:75, 1:100, 1:150, 1:200, 1:250, 1:300, 1:400, or 1:500. The first nucleic acid to be loaded and the further nucleic acid to be loaded may be present at a ratio of about 100:1, 75:1, 50:1, 25:1, 20:1, 15:1, 10:1, 9:1, 8:1, 7:1, 6:1, 5:1, 4:1, 3:1, 2:1, 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:15, 1:20, 1:25, 1:50, 1:75, 1:100, 1:150, 1:200, 1:250, 1:300, 1:400, or 1:500. The first nucleic acid to be loaded and the further nucleic acid to be loaded may be present at a ratio of about 25:1, 20:1, 15:1, 10:1, 9:1, 8:1, 7:1, 6:1, 5:1, 4:1, 3:1, 2:1, 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:15, 1:20, or 1:25. The first nucleic acid to be loaded and the further nucleic acid to be loaded may be present at a ratio of 1:1. [183] The first nucleic acid to be loaded and the further nucleic acid to be loaded may be present at a ratio of between 100:1-1:100, 75:1-1:75, 50:1-1:50, 25:1-1:25, 20:1-1:20, 15:1- 1:15, 10:1-1:10, 9:1-1:9, 8:1-1:8, 7:1-1:7, 6:1-1:6, 5:1-1:5, 4:1-1:4, 3:1-1:3, 2:1-1:2, or about 1:1. [184] In some embodiments where three non-identical nucleic acids are to be loaded into EVs, the first, second and third nucleic acids may be present in a ratio of about 1:1:2, 1:1:3, 1:1:4, 1:1:5, 1:1:6, 1:1:7, 1:1:8, 1:1:9, 1:1:10, 1:2:1, 1:3:1, 1:4:1, 1:5:1, 1:6:1, 1:7:1, 1:8:1, 1:9:1, 1:10:1, 2:1:1, 3:1:1, 4:1:1, 5:1:1, 6:1:1, 7:1:1, 8:1:1, 9:1:1, 10:1:1, 1:2:2, 1:3:3.1:4:4, 1:5:5, 1:6:6, 1:7:7.1:8:8: 1:9:9, 1:10:10, 1:2:3, 1:2:4, 1:3:6, 1:4:8, 1:5:10, 2:4:6, 2:8:4 or other ratio. [185] In some embodiments, the length of a nucleic acid to be loaded will influence the ratio. In some embodiments, a nucleic acid with longer length will be loaded at a greater ratio than a nucleic acid with less length. In some embodiments, the relative structure of a nucleic acid to be loaded will influence the ratio. In some embodiments, a more compact nucleic acid structure (e.g., a DNA plasmid) will be loaded at a lower ratio than a less compact nucleic acid structure (e.g., a linear DNA). In some embodiments, the strandedness (e.g. single or double) of a nucleic acid will influence the ratio. In some embodiments, a single-stranded nucleic acid will be loaded at a greater ratio than a double-stranded nucleic acid. In some embodiments, a single-stranded nucleic acid will be loaded at a doubled ratio than a double-stranded nucleic acid. The ratio maybe adjusted from 1:1 to 2:1 where the first nucleic acid is a single-stranded nucleic acid and the further nucleic acid is a double- stranded nucleic acid. Loading EVs with Cargo Nucleic Acids [186] In some embodiments, methods of EV loading comprise a step of loading the EVs with cargo nucleic acid. In some embodiments, prepared nucleic acid:transfection reagent complexes are contacted with the EVs that are to be loaded. In some embodiments, contacting with the EVs is performed subsequently to the contacting of the nucleic acid to be loaded with the transfection reagent. In some embodiments, the nucleic acid:transfection reagent complexes are contacted with a composition comprising a plurality of EVs. In some embodiments, the nucleic acid:transfection reagent complexes and EVs to be loaded are incubated for sufficient time and under appropriate conditions to allow the EV to be loaded with the one or more nucleic acid:transfection reagent complexes. In some embodiments, the nucleic acid:transfection reagent complexes are internalized into the EV. In some embodiments, the nucleic acid:transfection reagent complexes are loaded onto the surface of the EVs (e.g., onto the membranes of the EVs). [187] In some embodiments, EVs are isolated, washed, and/or concentrated after the step of loading with cargo nucleic acid. In some embodiments, loaded EVs are washed with phosphate buffered saline (PBS). In some embodiments, the washing step is repeated 1, 2, 3, 4, 5, 6, or more times. [188] In some embodiments, methods of EV loading comprise a temporary or semi- permanent increase in permeability of the membrane of the EVs. Suitable methods to temporarily or semi-permanently increase permeability of the EV membranes are, for example, electroporation, sonication, ultrasound, lipofection or hypotonic dialysis as described in PCT/SG2018/050596 which is herein incorporated by reference in its entirety. In some embodiments, loaded EVs are treated to increase the permeability of the membranes of the EVs. In some embodiments, the loaded EVs are chilled prior to treatment to increase the permeability of the membranes of the EVs. In some embodiments, treatment of the EVs to increase the permeability of the membranes of the EVs further involves one or more buffers (e.g., PBS). [189] In some embodiments, loading of EVs may be repeated. In some embodiments, EVs are further contacted with nucleic acid:transfection reagent complexes after previous contact with nucleic acid:transfection reagent complexes. In some embodiments, the further nucleic acid:transfection reagent complexes comprise a nucleic acid which is non-identical to the nucleic acid loaded in the previous loading step. In some embodiments, the further loading step is conducted under the same or different time and the same or different conditions as used in the previous loading step. A washing step may be performed after a first loading step and/or subsequent loading steps following the first loading step. Treatment to increase the permeability of the membranes of the EVs may be performed after a first loading step and/or subsequent loading steps following the first loading step. [190] In some embodiments, EVs are loaded with cargo nucleic acid by electroporation. Electroporation, or electropermeabilization, is a microbiology technique in which an electrical field is applied to cells in order to increase the permeability of the cell membrane, allowing, for example, chemicals, drugs or DNA to be introduced into the cell. In some embodiments, EVs are induced to encapsulate cargo nucleic acids by electroporation. In some embodiments, electroporation involves passing thousands of volts across a distance of one to two millimeters of suspended cells in an electroporation cuvette (1.0-1.5 kV, 250- 750V/cm). [191] In some embodiments, electroporation is a multi-step process with distinct phases. In some embodiments, a first phase comprises application of a short electrical pulse. In some embodiments, voltage settings for a fist phase would be within the range of 300-400 mV for less than 1 millisecond across the membrane. Application of the potential may charge the membrane like a capacitor through the migration of ions from the surrounding solution. There may be a rapid localized rearrangement in lipid morphology once the critical field is achieved. The resulting structure may not be electrically conductive but may lead to the rapid creation of a conductive pore. The conductive pores may heal by resealing the bilayer or expand and eventually rupture. In some embodiments, EVs are subjected to electroporation at between about 25 and 300 V or between about 50 and 250 V. [192] In some embodiments, EVs are loaded with cargo nucleic acid by sonication. Sonication is the act of applying sound energy to agitate particles in a sample. Ultrasonic frequencies (>20 kHz) may be used, leading to the process also being known as ultrasonification or ultra-sonification. Sonication may be applied using an ultrasonic bath or an ultrasonic probe, also known as a sonicator. [193] In some embodiments, EVs are loaded with cargo nucleic acid by ultrasound. Ultrasound is known to disrupt cell membranes and thereby load cells with molecules. Sound waves with frequencies from 20 kHz up to several gigahertz may be applied to EVs. [194] In some embodiments, EVs are loaded with cargo nucleic acid by lipofection. Lipofection, or liposome transfection, is a technique used to deliver nucleic acid into a cell by means of liposomes. Liposomes are vesicles that readily merge with phospholipid bilayers as liposomes are made of phospholipid bilayer. [195] In some embodiments, nucleic acids are loaded at an equimolar ratio when they are of similar size. In some embodiments, nucleic acids are loaded at an equimolar ratio when they are plasmids. In some embodiments, methods of EV loading comprise removing nucleic acid not contained within the lumen of EVs. In some embodiments, EVs are contacted with DNAse to remove nucleic acid not contained within the lumen of EVs. In some embodiments, EVs are contacted with heparin to dissociate nucleic acid or nucleic acid:transfection reagent complexes. V. Formulation and Administration [196] The present disclosure surprisingly demonstrates that EV populations (e.g., RBCEV populations) can be formulated for delivery to CNS sites, and can successfully be delivered to such sites. [197] In some embodiments, EV populations (e.g., RBCEV populations) are formulated for intrathecal administration (e.g., in a liquid that is compatible with cerebrospinal fluid). In some embodiments, intrathecal administration of an EV population (e.g., an RBCEV population) results in expression of a payload nucleic acid in CNS tissues. In some embodiments, intrathecal administration of an EV population (e.g., an RBCEV population) results in sustained expression of a payload nucleic acid in CNS tissues (e.g., for 1, 2, 3, 4, 5, 6, 7, or more days). In some embodiments, intrathecal administration of an EV population (e.g., an RBCEV population) results in expression of a payload nucleic acid in particular organs and/or regions of CNS tissues (e.g., cerebellum, spinal cord, etc.). In some embodiments, intrathecal administration of an EV population (e.g., an RBCEV population) results in expression of a payload nucleic acid in particular cell types of CNS tissues (e.g., neuronal cells, Purkinje cells, etc.). In some embodiments, intrathecal administration of an EV population (e.g., an RBCEV population) results in secretion of a product encoded by a payload nucleic acid from CNS tissues. In some embodiments, intrathecal administration of an EV population (e.g., an RBCEV population) does not result in toxicity. EXEMPLIFICATION Example 1: CNS Delivery [198] The present Example documents effective delivery of nucleic acid cargo from extracellular vesicles (specifically, RBCEVs) to the CNS. Materials and Methods Animals Male [199] C57BL/6 mice weighted about 20-25 g (Invivos, Singapore) were used in this study. Animals were housed in groups of three to five per cage and maintained in a 12 h light/dark cycle in a temperature-controlled and humidity-controlled facility. Standard chow and water were provided ad libitum. The experimental procedures were approved by the Institutional Animal Care and Use Committee (IACUC) at the National University of Singapore. Intrathecal Drug Administration [200] RBCEVs were dissolved in PBS (10 µg/µL).10 µl RBCEVs were intrathecally injected into the L5-L6 intervertebral space of the mice (4-6 weeks). The control group did not receive intrathecal injection. Buprenorphine (0.3 mg/mL) were injected subcutaneously into the mice at 0.1 mL/kg right before intrathecal injection and once every 12 h if required. Determination of EV uptake and biodistribution in vivo [201] 100 µg DiR-CFSE-labelled EVs (10 µg/µ; DiR 1,1'-Dioctadecyl-3,3,3',3'- Tetramethylindotricarbocyanine Iodide; CFSE Carboxyfluorescein succinimidyl ester) were intrathecally injected into the mice. The mice were sacrificed 24 h post injection and organs were collected for DiR fluorescence imaging using the IVIS® Lumina III system. Then, the organs were fixed in 10 % formalin, immersed in 15 % and 30 % sucrose solutions, and embedded in OCT using dry ice. Tissues were stored in -80°C until required. Determination of luciferase expression of CMV-Luc-loaded EVs in vivo [202] 100 µg CMV-Luc-loaded EVs (10 µg/µL) were intrathecally injected in the mice. After 48 h, D-luciferin (150 mg/kg) were injected intraperitoneally to detect luciferase activity using IVIS® Lumina III system for six consecutive days. On Day 9, the brains and spinal cords of mice were collected, and immersed in D-luciferin solution (150 µg/mL final concentration) for at least 5 min before fluorescence imaging using IVIS® Lumina III system. Then the organs were fixed in 10 % formalin, immersed in 15 % and 30 % sucrose solutions, and embedded in OCT using dry ice. Tissues were stored in -80°C until required. Determination of GFP expression of GFAP-GFP-loaded EVs in vivo [203] 100 µg GFAP-GFP-loaded EVs (10 µg/µL) were intrathecally injected in the mice. The mice were sacrificed 48 h post injection and organs were collected for fluorescence imaging using IVIS® Lumina III system. Then, the organs were fixed in 10 % formalin, immersed in 15 % and 30 % sucrose solutions, and embedded in OCT using dry ice. Tissues were stored in -80°C until required. Immunohistochemistry [204] The embedded tissues were cut to a 6-µm thickness, and collected on Superfrost slides. The slides were then washed in PBS, blocked with 2.5 % BSA, 0.1 % Triton X-100 for 1 h, incubated with the primary antibodies in blocking buffer at 4°C overnight, washed in PBS, incubated with appropriate secondary antibodies in blocking buffer at room temperature for 1 h, counterstained with Hoechst33342 for 5 min, and mounted in anti-fade solution. Images were captured with Olympus FV3000 confocal microscope. Isolation of primary astrocytes [205] Pre-frontal cortexes from P1 pups were collected, and meninges were removed under a dissecting microscope. The tissues were digested in a trypsin/DNase solution (25 mg/mL trypsin and 0.15mg/mL DNase) for 30 min in the incubator (37°C, 5 % CO ₂ ). Digested cells were spun at 500 xg for 5 min in a swinging-bucket centrifuge. The cells were resuspended in DMEM supplemented with 10 % FBS, 1 % pen/strep and 1 % L-glutamine and passed through a 70 µm and 40 µm filters consecutively. The cells were seeded in 10-cm tissue culture treated flask coated with collagen in DMEM supplemented with 10 % FBS, 1 % pen/strep and 1 % L-glutamine. The media was changed once every 2-3 days. Once confluent, microglial cells were removed by gently shaking the flask at 180 rpm on an orbital shaker for 30 min, aspiration and removal of the media. Then, oligodendrocyte progenitor cells are removed by shaking the flask at 240 rpm for 5-6 h. Determination of tdTomato expression of CMV-tdTomato-loaded EVs ex vivo [206] Primary astrocytes were seeded at 5 x 10 ⁵ cells per well in 24-well plate the day before treatment.20 µg CMV-tdTomato-loaded EVs were added to the cells for 48 h, washed with PBS, and resuspended in FACS buffer (1 % FBS in PBS) before flow cytometric analysis. Results [207] EVs, labelled with DiR and/or CFSE, were delivered to the central nervous system (CNS) via intrathecal injection (Figure 1A). After 24 h, the mice were sacrificed and organs were collected to measure the DiR signal using an in vivo imaging system (IVIS). The data show that EVs were localized to the brain and spinal cord 24 h post intrathecal injection (Figure 1B-C). Furthermore, some EVs localization to the spleen and liver was observed for the mice receiving DiR-CFSE-labelled EVs. Immune-histology results revealed that EVs were localized to neurons, activated astrocytes, and activated microglia cells (Figure 1D). [208] EVs were loaded with CMV-luciferase plasmids and injected into C57BL/6 mice (Figure 2A). As compared to untreated mice, CMV-Luc-EVs mice displayed bioluminescence signal along the brain and spinal cord two days post intrathecal injection (Figure 2B). The bioluminescence signal at the spinal cord peaked at around four to five days after the injection. Immuno-histology analysis revealed that luciferase was still expressed in cells location in the spinal cord, frontal lobe, cingulate gyrus, and hind brain nine days post injection (Figure 2C-F). [209] EVs were loaded with a GFAP-GFP-plasmid and injected into C57BL/6 mice (Figure 3A). The mice were sacrificed 48 h post injection and the brains were collected for fluorescence imaging. As compared to brain of the untreated mice, GFAP-GFP-EVs mice displayed fluorescence signal in the brain (Figure 3B). Immuno-histology analysis also revealed that GFP was indeed expressed in the brain (Figure 3C-D). The in vivo data were validated using primary astrocytes as GFAP is an astrocyte-specific promoter in the brain. Primary astrocytes were collected from P1 pups and cultured for up to seven days before incubation with CMV-tdTomato plasmid-loaded EVs (Figure 3E). Flow cytometric analysis revealed that tdTomato was indeed expressed in these primary astrocytes 48 h post incubation. Summary [210] Therapeutic RNA oligonucleotides are being used to treat many diseases which were once considered undruggable (Chery, 2016; Dammes & Peer, 2020; Sehgal et al., 2013). However, these treatments are restricted by the inefficient delivery of these molecules to target cells (Dammes & Peer, 2020). Fortunately, RBCEVs have been demonstrated to be effective carriers of RNA oligonucleotides and, for example, to deliver antisense oligonucleotides and achieve efficient knock down of miR-125b, resulting in inhibition of tumour growth in human breast cancer and acute myeloid leukaemia xenograft mouse models via intra-tumoral and systemic administration respectively (Usman et al., 2018). No toxicity associated with RBCEV treatments was observed in those studies. [211] The present Example describes effective delivery to CNS sites of plasmids carrying markers which can be detected with fluorescence microscopy by RBCEVs that were delivered using intrathecal injection (i.e., a direct injection of therapeutic materials into the cerebrospinal fluid that bypasses the blood brain barrier). The present Example documents that such intrathecal injection can be used to deliver RBCEVs into the CNS, and furthermore demonstrates uptake up by various CNS cell types. [212] The present Example also demonstrates that plasmids delivered by RBCEVs can be expressed by cells for up to seven days, and cargo (specifically, in this example, luciferase) expression can be found in various parts of the CNS. [213] The present Example further demonstrates that plasmids can be delivered to astrocytes in vivo (using a cell-specific promoter) and ex vivo. Example 2: CNS Delivery [214] The present Example documents effective delivery of nucleic acid cargo from extracellular vesicles (specifically, RBCEVs) to the CNS. [215] Fluorescently labeled RBCEVs were injected intrathecally to investigate if intrathecal delivery could enhance the uptake of RBCEVs by cells in the central nervous system (CNS; Figure 4A). At 24 hours after intrathecal delivery of DiR-CFSE-labeled RBCEVs, ex vivo imaging analysis revealed a distinct DiR signal in the vertebral column, brain, liver, and spleen, in order of decreasing intensity (Figure 4B). Furthermore, CFSE- labeled RBCEVs were identified in neurons, astrocytes, and microglia through immunostaining using cell-specific markers (Figure 5). These findings demonstrate that intrathecal delivery can facilitate the localization of RBCEVs in the CNS and enable their uptake by major cell types within the CNS. [216] After demonstrating the potential of an RBCEV platform (e.g., as described herein) for delivering plasmids into the CNS, a luciferase-based plasmid reporter system was utilized to evaluate its functional delivery capacity. First, RBCEVs loaded with a CMV- luciferase nano-plasmid were administered into C57BL/6 mice through intrathecal injection (Figure 6A). Increased bioluminescence signals were observed from day 2 to day 5 in treated mice compared to untreated mice (Figure 6B). However, the signal began to decline from day 5 after the treatment. An ex vivo luciferase assay was conducted seven days post- treatment and observed a substantial luciferase activity in the brains and spinal cords of the treated mice but not in the untreated mice (Figure 6C). Finally, we collected CNS tissue samples for immunostaining with an anti-luciferase antibody. Microscopy of the stained sections confirmed the luciferase protein expression in the cerebellum, cerebral cortex, and cingulate gyrus of the treated mice (Figure 7). These findings confirm that RBCEVs can effectively deliver plasmids for gene expression in the CNS of immunocompetent mice. [217] Furthermore, luciferase plasmids with different promoters (CMV and CAG) were compared and bioluminescence was observed for 2 weeks (Figure 8A). Bodyweight was used as an assessment for general toxicity, and liver tissues were also collected at the end of the treatment to evaluate toxicity. Consistent with previous experiments, mice treated with CMV-Luc-plasmid-loaded EVs showed increased bioluminescence signals from day 3 to 5 (Figure 8B-C). Compared to the CMV-Luc-EV-treated mice, CAG-Luc-EV-treated mice had a lower average bioluminescent signal even though the trend was the same. Furthermore, weight change did not fluctuate much throughout the treatment duration (Figure 8D). These data demonstrate that RBCEVs can deliver plasmids with CMV and CAG promoters for gene expression in the CNS of C57BL/6 mice. [218] An eGFP-based plasmid reporter system was used to further evaluate the capacity of the RBCEV-delivery platform in mediating GFP expression. First, CAG-eGFP nano- plasmid-loaded RBCEVs were administered into C57BL/6 mice via intrathecal injection (Figure 9A). Subsequently, CNS tissue samples were collected for immunostaining with several cell-specific markers. Remarkably, clear GFP protein expression was observed in Calbindin-positive Purkinje cells in the cerebellum and NeuN-positive neuronal cells in the spinal cord of the treated mice, as shown by the colocalization of GFP with Calbindin and NeuN (Figure 9B-C). By contrast, little colocalization of GFP with GFAP was observed, GFAP being a marker for astrocytes. These findings demonstrate that RBCEVs can effectively deliver plasmids for gene expression in neurons and Purkinje cells of C57BL/6 mice. [219] Finally, a Nanoluc-based plasmid reporter system was utilized to assess the potential for transgene products to be secreted after administration of CAG-tdtomato Nanoluc nano- plasmid-loaded RBCEVs into C57BL/6 mice through intrathecal injection (Figure 10A). Cerebrospinal fluid (CSF), serum, brain, and spinal samples were collected for an analysis of the secreted luciferase protein three days post-treatment. A significant increase in luciferase signals was observed in both serum and CSF samples from Nanoluc-RBCEV treated mice (Figure 10B-C). Additionally, a substantial rise in luciferase signal was detected in the lysate of the lumbar and thoracic regions of the spinal cord (Figure 10D). A marked increase in luciferase signal was also found in the cervical region of the spinal cord and the brain (Figure 10D-E). These results show that intrathecally-injected RBCEVs can efficiently transport plasmids, leading to protein expression and secretion in C57BL/6 mice. [220] To assess the potential of RBCEVs to deliver anti-sense oligonucleotide (ASO) to CNS site(s), several ASOs were designed and validated for GAPDH knockdown in vitro and then ASO-loaded RBCEVs were administered to C57BL/6 mice through intrathecal injection (Figure 11A). The spinal cord and brain samples were collected for molecular analysis of mRNA knock down two days post-treatment. Using qPCR, a significant knock down of GAPDH was observed in both the spinal cord and brain (Figure 11B-C). These results show that RBCEVs can efficiently transport ASO to CNS site(s), leading to gene silencing in C57BL/6 mice. REFERENCES CITED Chery, J.2016. RNA therapeutics: RNAi and antisense mechanisms and clinical applications. Postdoc J.2016 Jul;4(7):35-50. doi: 10.14304/surya.jpr.v4n7.5. PMID: 27570789; PMCID: PMC4995773. Dammes N, Peer D. Paving the Road for RNA Therapeutics. Trends Pharmacol Sci.2020 Oct;41(10):755-775. doi: 10.1016/j.tips.2020.08.004. Epub 2020 Sep 3. PMID: 32893005; PMCID: PMC7470715. Usman, W.M., Pham, T.C., Kwok, Y.Y. et al. Efficient RNA drug delivery using red blood cell extracellular vesicles. Nat Commun 9, 2359 (2018). https://doi.org/10.1038/s41467-018-04791-8.

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 invention described herein. It is to be understood that the invention encompasses all variations, combinations, and permutations in which one or more limitations, elements, clauses, descriptive terms, etc., from one or more of the listed claims is introduced into another claim dependent on the same base claim (or, as relevant, any other claim) unless otherwise indicated or unless it would be evident to one of ordinary skill in the art that a contradiction or inconsistency would arise. Further, it should also be understood that any embodiment or aspect of the invention can be explicitly excluded from the claims, regardless of whether the specific exclusion is recited in the specification. The scope of the present invention is not intended to be limited to the above Description, but rather is as set forth in the claims that follow. It must be noted that, as used in the specification and the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise. Ranges may be expressed herein as from “about” one particular value, and/or to “about” another particular value. When such a range is expressed, another embodiment includes from the one particular value and/or to the other particular value. Similarly, when values are expressed as approximations, by the use of the antecedent “about,” it will be understood that the particular value forms another embodiment. The term “about” in relation to a numerical value is optional and means for example +/- 10%.