WO2023039175A2 - Predictors of achromatopsia treatment efficacy - Google Patents

Abstract

The present invention provides methods for treating or selecting a subject for treatment of a retinal disease or disorder, including, without limitation, achromatopsia (ACHM), based on an analysis of the subject's retinal structure and/or function.

Description

PREDICTORS OF ACHROMATOPSIA TREATMENT EFFICACY RELATED APPLICATIONS This application claims the benefit of priority to U.S. Provisional Application No. 63/242,448, filed on September 9, 2021, the entire contents of which are incorporated herein by reference. FIELD OF THE INVENTION The present invention relates to methods for treating or selecting a subject for treatment of a retinal disease or disorder, including, without limitation, achromatopsia (ACHM), based on an analysis of the subject’s retinal structure and/or function. BACKGROUND Achromatopsia (ACHM) is a color vision disorder, which is typically a congenital autosomal recessive disorder. It may be partial or complete. See Pang et al. Advances in Experimental Medicine and Biology, 664(6): 639-646 (2010) (hereinafter “Pang et al.”). Symptoms of achromatopsia include, for example, reduced visual acuity, achromatopia (lack of color perception), hemeralopia (reduced visual capacity in bright light accompanied by photoaversion, meaning a dislike or avoidance of bright light), nystagmus (uncontrolled oscillatory movement of the eyes), iris operating abnormalities, and impaired stereovision (inability to perceive three-dimensional aspects of a scene). Electroretinograms reveal that in achromatopsia, the function of retinal rod photoreceptors remains intact, whereas retinal cone photoreceptors are not functional. The rod and cone photoreceptors serve functionally different roles in vision. Pang et al. Cone photoreceptors are primarily responsible for central, fine resolution and color vision while operating in low to very bright light. They are concentrated in the central macula of the retina and comprise nearly 100% of the fovea. Rod photoreceptors are responsible for peripheral, low light, and night vision; they are found primarily outside the macula in the peripheral retina. Approximately 1 in 30,000 individuals suffers from complete achromatopsia. In complete achromatopsia, there is total color vision loss, central vision loss, and visual acuity of 20/200 or worse. Thus, most individuals with achromatopsia are legally blind. The current standard of care consists of limiting retinal light exposure with tinted contact lenses and providing magnification to boost central vision. However, there is no treatment available that corrects cone function in achromatopsia. Pang et al. There are various genetic causes of congenital achromatopsia. Mutations in the cyclic nucleotide-gated ion channel beta 3 (CNGB3) gene or in the cyclic nucleotide-gated ion channel alpha 3 (CNGA3) gene, are exemplary genetic causes of achromatopsia. Mutations in CNGB3 account for approximately 50% of patients, while mutations in CNGA3 account for approximately 25% of patients. However, few reliable predictors of efficacy are available to guide the selection of particular agents for the optimal treatment of individual subjects. The present invention addresses the need for an effective achromatopsia treatment. SUMMARY In one aspect, the instant invention provides a method of treating a subject, comprising: (a) selecting the subject if a predetermined pattern of fundus autofluorescence (FAF) is present in an eye of the subject at baseline; and (b) administering to the subject an effective amount of a therapy suitable for treating achromatopsia (ACHM). In one aspect, the instant invention provides a method of selecting and treating a subject predisposed to achromatopsia (ACHM), comprising: (a) selecting the subject if a predetermined pattern of fundus autofluorescence (FAF) is present in an eye of the subject at baseline; and (b) administering to the subject an effective amount of a therapy suitable for treating achromatopsia (ACHM). In one aspect, the instant invention provides a method of selecting and treating a subject having achromatopsia (ACHM) that is likely to be a visual field responder, comprising: (a) selecting the subject if a predetermined pattern of fundus autofluorescence (FAF) is present in an eye of the subject at baseline; and (b) administering to the subject an effective amount of a therapy suitable for treating achromatopsia (ACHM). In one aspect, the instant invention provides a method of reducing, inhibiting and/or preventing one or more symptoms of achromatopsia (ACHM) in a subject, comprising: (a) selecting the subject if a predetermined pattern of fundus autofluorescence (FAF) is present in an eye of the subject at baseline; and (b) administering to the subject an effective amount of a therapy suitable for treating achromatopsia (ACHM). In certain embodiments of any one of the preceding aspects, the method further comprising classifying the pattern of fundus autofluorescence (FAF) in the eye of the subject as comprising central hypoautofluorescence (grade 0), normal autofluorescence (grade 1), or mild or strong hyperautofluorescence (grade 2). In certain embodiments of any one of the preceding aspects, wherein: (a) a pattern of FAF comprising central hypoautofluorescence (grade 0) identifies a subject that is less likely to be a visual field responder; (b) a pattern of FAF comprising normal autofluorescence (grade 1) identifies a subject that is less likely to be a visual field responder; and/or (c) a pattern of FAF comprising mild or strong hyperautofluorescence (grade 2) identifies a subject that is more likely to be a visual field responder. In certain embodiments of any one of the preceding aspects, wherein the predetermined pattern of fundus autofluorescence (FAF) is mild or strong hyperautofluorescence (grade 2). In certain embodiments of any one of the preceding aspects, wherein the predetermined pattern of fundus autofluorescence (FAF) in the eye of the subject is obtained prior to or at the time of administration of the therapy suitable for treating achromatopsia (ACHM). In certain embodiments of any one of the preceding aspects, further comprising monitoring the pattern of fundus autofluorescence (FAF) in the eye of the subject for a period of time after administration of the therapy suitable for treating achromatopsia (ACHM). In one aspect, the instant invention provides a method of treating a subject, comprising: (a) selecting the subject if a predetermined optical coherence tomography (OCT) central outer retina morphology is present in an eye of the subject at baseline; and (b) administering to the subject an effective amount of a therapy suitable for treating achromatopsia (ACHM). In one aspect, the instant invention provides a method of selecting and treating a subject predisposed to achromatopsia (ACHM), comprising: (a) selecting the subject if a predetermined optical coherence tomography (OCT) central outer retina morphology is present in an eye of the subject at baseline; and (b) administering to the subject an effective amount of a therapy suitable for treating achromatopsia (ACHM). In one aspect, the instant invention provides a method of selecting and treating a subject having achromatopsia (ACHM) that is more likely to be a visual field responder, comprising: (a) selecting the subject if a predetermined optical coherence tomography (OCT) central outer retina morphology is present in an eye of the subject at baseline; and (b) administering to the subject an effective amount of a therapy suitable for treating achromatopsia (ACHM). In one aspect, the instant invention provides a method of reducing, inhibiting and/or preventing one or more symptoms of achromatopsia (ACHM) in a subject, comprising: (a) selecting the subject if a predetermined optical coherence tomography (OCT) central outer retina morphology is present in an eye of the subject at baseline; and (b) administering to the subject an effective amount of a therapy suitable for treating achromatopsia (ACHM). In certain embodiments of any one of the preceding aspects, further comprising classifying the optical coherence tomography (OCT) central outer retina morphology in the eye of the subject as comprising central absence of ellipsoid zone (EZ) line disturbance (grade 0), the presence of EZ line disturbance (grade 1), or the presence of empty optical space (grade 2). In certain embodiments of any one of the preceding aspects, wherein: (a) an OCT central outer retina morphology comprising the central absence of ellipsoid zone (EZ) line disturbance (grade 0) identifies a subject that is more likely to be a visual field responder; (b) an OCT central outer retina morphology comprising the presence of EZ line disturbance (grade 1) identifies a subject that is more likely to be a visual field responder; and/or (c) an OCT central outer retina morphology comprising the presence of empty optical space (grade 2) identifies a subject that is less likely to be a visual field responder. In certain embodiments of any one of the preceding aspects, wherein the predetermined optical coherence tomography (OCT) central outer retina morphology is central absence of ellipsoid zone (EZ) line disturbance (grade 0) or presence of EZ line disturbance (grade 1). In certain embodiments of any one of the preceding aspects, wherein the predetermined optical coherence tomography (OCT) central outer retina morphology in the eye of the subject is obtained prior to or at the time of administration of the therapy suitable for treating achromatopsia (ACHM). In certain embodiments of any one of the preceding aspects, further comprising monitoring the optical coherence tomography (OCT) central outer retina morphology in the eye of the subject for a period of time after administration of the therapy suitable for treating achromatopsia (ACHM). In certain embodiments of any one of the preceding aspects, further comprising testing the subject for a visual field response. In certain embodiments of any one of the preceding aspects, wherein the subject is a visual field responder. In certain embodiments of any one of the preceding aspects, wherein the subject is suffering from achromatopsia (ACHM). In certain embodiments of any one of the preceding aspects, wherein the subject has at least one mutation in an achromatopsia (ACHM)-associated gene selected from the group consisting of ATF6, CNGA3, CNGB3, GNAT2, PDE6C, and PDE6H. In certain embodiments of any one of the preceding aspects, which results in the amelioration of one or more symptoms of achromatopsia (ACHM). In certain embodiments of any one of the preceding aspects, which results in a decrease in central hyperautofluorescence, optionally, as compared to a baseline measurement. In certain embodiments of any one of the preceding aspects, wherein the one or more symptoms of a d achromatopsia (ACHM) is selected from the group consisting of a reduced visual acuity, a pendular nystagmus, an increased sensitivity to light (photophobia), a small central scotoma, and/or a reduced or complete loss of color discrimination. In certain embodiments of any one of the preceding aspects, which results in an improvement in visual sensitivity measured by static perimetry, optionally, as compared to a baseline measurement. In certain embodiments of any one of the preceding aspects, which results in an improvement in light discomfort thresholds measured using an ocular photosensitivity analyzer (OPA), optionally, as compared to a baseline measurement. In certain embodiments of any one of the preceding aspects, which results in an improvement in electrical signaling in the retina as measured by multi-focal electroretinography (mfERG), optionally, as compared to a baseline measurement. In certain embodiments of any one of the preceding aspects, wherein the improvement in visual sensitivity, light discomfort thresholds, and/or electrical signaling in the retina is maintained over a period of time comprising at least about 1 month or more. In certain embodiments of any one of the preceding aspects, wherein the improvement in visual sensitivity, light discomfort thresholds, and/or electrical signaling in the retina is maintained for the lifetime of the subject. In certain embodiments of any one of the preceding aspects, wherein the therapy suitable for treating achromatopsia (ACHM) comprises a gene therapy. In certain embodiments of any one of the preceding aspects, wherein the gene therapy comprises a nucleic acid sequence encoding an achromatopsia (ACHM)-associated gene. In certain embodiments of any one of the preceding aspects, wherein the achromatopsia (ACHM)-associated gene is selected from the group consisting of ATF6, CNGA3, CNGB3, GNAT2, PDE6C, and PDE6H. In certain embodiments of any one of the preceding aspects, wherein the nucleic acid sequence is codon optimized for mammalian expression. In certain embodiments of any one of the preceding aspects, wherein: (i) the nucleic acid sequence comprises SEQ ID NO: 1, or a sequence at least 85% identical to SEQ ID NO: 1; or (i) the nucleic acid sequence comprises SEQ ID NO: 150, or a sequence at least 85% identical to SEQ ID NO: 150. In certain embodiments of any one of the preceding aspects, wherein the nucleic acid sequence is a cDNA sequence. In certain embodiments of any one of the preceding aspects, wherein the nucleic acid sequence is operably linked to a promoter. In certain embodiments of any one of the preceding aspects, wherein the promoter comprises a PR1.7 promoter (SEQ ID NO: 2). In certain embodiments of any one of the preceding aspects, wherein the nucleic acid sequence further comprises an operably linked minimal regulatory element. In certain embodiments of any one of the preceding aspects, wherein the minimal regulatory element comprises a polyadenylation site, splicing signal sequences, and/or AAV inverted terminal repeats. In certain embodiments of any one of the preceding aspects, wherein the nucleic acid sequence further comprises an operably linked polyadenylation signal (pA), optionally, a SV(40) polyA. In certain embodiments of any one of the preceding aspects, wherein the gene therapy comprises a vector. In certain embodiments of any one of the preceding aspects, wherein the vector is an adeno-associated viral (AAV) vector. In certain embodiments of any one of the preceding aspects, wherein the serotype of the capsid sequence and the serotype of the ITRs of said AAV vector are independently selected from the group consisting of AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10, AAV11, and AAV12. In certain embodiments of any one of the preceding aspects, wherein the capsid sequence is a mutant capsid sequence. In certain embodiments of any one of the preceding aspects, wherein the vector comprises a recombinant adeno-associated (rAAV) expression vector. In certain embodiments of any one of the preceding aspects, wherein the vector comprises a transgene expression cassette comprising a promoter; an achromatopsia (ACHM)- associated gene nucleic acid; and minimal regulatory elements. In certain embodiments of any one of the preceding aspects, wherein the minimal regulatory elements comprise a polyadenylation site, splicing signal sequences, and/or AAV inverted terminal repeats. In certain embodiments of any one of the preceding aspects, wherein the minimal regulatory elements comprise a poly adenylation (SV40 poly A) signal and flanking AAV inverted terminal repeats (ITR). In certain embodiments of any one of the preceding aspects, wherein the serotype of the capsid sequence and the serotype of the ITRs of said AAV vector are independently selected from the group consisting of AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10, AAV11, and AAV12. In certain embodiments of any one of the preceding aspects, wherein the serotype of the capsid sequence is AAV2. In certain embodiments of any one of the preceding aspects, wherein the capsid sequence is a mutant capsid sequence. In certain embodiments of any one of the preceding aspects, wherein the vector is administered to the subject subretinally. BRIEF DESCRIPTION OF THE DRAWINGS FIG.1 shows images of representative study eyes that were classified into central hypoautofluorescence (grade 0), normal autofluorescence (grade 1), and mild or strong hyperautofluorescence (grade 2). FIG.2 show images of representative study eyes from Subject 4029, which presented stippled central hyperautofluorescence at baseline which gradually decreased after study treatment only in the study eye. FIG.3 show images of representative fellow eye from Subject 4029. FIG.4 show images of representative study eyes that were classified into central absence of EZ line disturbance (grade 0), presence of EZ line disturbance (grade 1), or presence of empty optical space (grade 2). FIG.5 shows a table summarizing the results of an analysis of OCT outer retina grading as compared to Octopus visual field response, which suggests a different distribution of OCT outer retina categories between studies. In the ACHM B3 study, more than two thirds of study eyes were classified as grade 0. In the ACHM A3 study, less than a third presented the same grading. DETAILED DESCRIPTION I. Definitions This disclosure is not limited to the particular methodology, protocols, cell lines, vectors, or reagents described herein because they may vary. Further, the terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the scope of the present disclosure. Unless defined otherwise, all technical and scientific terms and any acronyms used herein have the same meanings as commonly understood by one of ordinary skill in the art in the field of the invention. Although any methods and materials similar or equivalent to those described herein can be used in the practice of the present disclosure, the exemplary methods, devices, and materials are described herein. Unless defined otherwise, all technical and scientific terms used herein have the meaning commonly understood by a person skilled in the art to which this disclosure belongs. The following references provide one of skill with a general definition of many of the terms used in this disclosure: Singleton et al., Dictionary of Microbiology and Molecular Biology (2nd ed. 1994); The Cambridge Dictionary of Science and Technology (Walker ed., 1988); The Glossary of Genetics, 5th Ed., R. Rieger et al. (eds.), Springer Verlag (1991); and Hale & Marham, The Harper Collins Dictionary of Biology (1991). As used herein, the following terms have the meanings ascribed to them below, unless specified otherwise. The articles “a” and “an” are used herein to refer to one or to more than one (i.e. to at least one) of the grammatical object of the article. By way of example, “an element” means one element or more than one element. As used in this specification and the appended claims, the singular forms “a,” “an,” and “the” include plural references unless the context clearly dictates otherwise. Thus, for example, references to “the method” includes one or more methods, and/or steps of the type described herein and/or which will become apparent to those persons skilled in the art upon reading this disclosure and so forth. Similarly, the word “or” is intended to include "and" unless the context clearly indicates otherwise. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of this disclosure, suitable methods and materials are described below. The abbreviation, “e.g.” is derived from the Latin exempli gratia, and is used herein to indicate a non-limiting example. Thus, the abbreviation “e.g.” is synonymous with the term “for example.” Groupings of alternative elements or embodiments of the invention disclosed herein are not to be construed as limitations. Each group member can be referred to and claimed individually or in any combination with other members of the group or other elements found herein. One or more members of a group can be included in, or deleted from, a group for reasons of convenience and/or patentability. When any such inclusion or deletion occurs, the specification is herein deemed to contain the group as modified thus fulfilling the written description of all Markush groups used in the appended claims. The term “including” is used herein to mean, and is used interchangeably with, the phrase “including but not limited to”. The term “or” is used herein to mean, and is used interchangeably with, the term “and/or,” unless context clearly indicates otherwise. The term “such as” is used herein to mean, and is used interchangeably, with the phrase “such as but not limited to”. As used herein, the terms “administer,” “administering,” “administration,” and the like, are meant to refer to methods that are used to enable delivery of therapeutics or pharmaceutical compositions to the desired site of biological action. According to certain embodiments, these methods include subretinal injection, suprachoroidal injection or intravitreal injection to an eye. As used herein, the term “AAV virion” is meant to refer broadly to a complete virus particle, such as for example a wild type AAV virion particle, which comprises single stranded genome DNA packaged into AAV capsid proteins. The single stranded nucleic acid molecule is either sense strand or antisense strand, as both strands are equally infectious. The term “rAAV viral particle” refers to a recombinant AAV virus particle, i.e., a particle that is infectious but replication defective. A rAAV viral particle comprises single stranded genome DNA packaged into AAV capsid proteins. “Achromatopsia” is a color vision disorder. Symptoms of achromatopsia include achromatopia (lack of color perception), amblyopia (reduced visual acuity), hemeralopia (reduced visual capacity in bright light accompanied by photoaversion, meaning a dislike or avoidance of bright light), nystagmus (uncontrolled oscillatory movement of the eyes), iris operating abnormalities, and impaired stereovision (inability to perceive three-dimensional aspects of a scene). As used herein, the term “achromatopsia” refers to a form of achromatopsia caused by genetic mutations, substitutions, or deletions. As used herein, the term “carrier” is meant to include any and all solvents, dispersion media, vehicles, coatings, diluents, antibacterial and antifungal agents, isotonic and absorption delaying agents, buffers, carrier solutions, suspensions, colloids, and the like. The use of such media and agents for pharmaceutically active substances is well known in the art. Supplementary active ingredients can also be incorporated into the compositions. The phrase “pharmaceutically-acceptable” refers to molecular entities and compositions that do not produce a toxic, an allergic, or similar untoward reaction when administered to a host. As used herein, the terms “expression vector”, “vector” or “plasmid” can include any type of genetic construct, including AAV or rAAV vectors, containing a nucleic acid or polynucleotide coding for a gene product in which part or all of the nucleic acid encoding sequence is capable of being transcribed and is adapted for gene therapy. The transcript can be translated into a protein. In some instances, it may be partially translated or not translated. In certain embodiments, expression includes both transcription of a gene and translation of mRNA into a gene product. In other embodiments, expression only includes transcription of the nucleic acid encoding genes of interest. An expression vector can also comprise control elements operatively linked to the encoding region to facilitate expression of the protein in target cells. The combination of control elements and a gene or genes to which they are operably linked for expression can sometimes be referred to as an “expression cassette.” As used herein, the term “flanking” refers to a relative position of one nucleic acid sequence with respect to another nucleic acid sequence. Generally, in the sequence ABC, B is flanked by A and C. The same is true for the arrangement AxBxC. Thus, a flanking sequence precedes or follows a flanked sequence but need not be contiguous with, or immediately adjacent to the flanked sequence. As used herein, the term “gene delivery” means a process by which foreign DNA is transferred to host cells for applications of gene therapy. As used herein, the term “heterologous” means derived from a genotypically distinct entity from that of the rest of the entity to which it is compared or into which it is introduced or incorporated. For example, a polynucleotide introduced by genetic engineering techniques into a different cell type is a heterologous polynucleotide (and, when expressed, can encode a heterologous polypeptide). Similarly, a cellular sequence (e.g., a gene or portion thereof) that is incorporated into a viral vector is a heterologous nucleotide sequence with respect to the vector. As used herein, the term “increase,” “enhance,” “raise” (and like terms) generally refers to the act of increasing, either directly or indirectly, a concentration, level, function, activity, or behavior relative to the natural, expected, or average, or relative to a control condition. As used herein, the term “inverted terminal repeat” or “ITR” sequence is meant to refer to relatively short sequences found at the termini of viral genomes which are in opposite orientation. An “AAV inverted terminal repeat (ITR)” sequence, a term well-understood in the art, is an approximately 145-nucleotide sequence that is present at both termini of the native single-stranded AAV genome. The outermost 145 nucleotides of the ITR can be present in either of two alternative orientations, leading to heterogeneity between different AAV genomes and between the two ends of a single AAV genome. The outermost 145 nucleotides also contain several shorter regions of self-complementarity (designated A, A', B, B', C, C' and D regions), allowing intrastrand base-pairing to occur within this portion of the ITR. A “wild-type ITR” ,“WT-ITR” or “ITR” refers to the sequence of a naturally occurring ITR sequence in an AAV or other Dependovirus that retains, e.g., Rep binding activity and Rep nicking ability. The nucleotide sequence of a WT-ITR from any AAV serotype may slightly vary from the canonical naturally occurring sequence due to degeneracy of the genetic code or drift, and therefore WT-ITR sequences encompassed for use herein include WT-ITR sequences as result of naturally occurring changes taking place during the production process (e.g., a replication error). As used herein, the term “terminal repeat” or “TR” includes any viral terminal repeat or synthetic sequence that comprises at least one minimal required origin of replication and a region comprising a palindrome hairpin structure. A Rep-binding sequence (“RBS”) (also referred to as RBE (Rep-binding element)) and a terminal resolution site (“TRS”) together constitute a “minimal required origin of replication” and thus the TR comprises at least one RBS and at least one TRS. TRs that are the inverse complement of one another within a given stretch of polynucleotide sequence are typically each referred to as an “inverted terminal repeat” or “ITR”. In the context of a virus, ITRs mediate replication, virus packaging, integration and provirus rescue. The term “in vivo” refers to assays or processes that occur in or within an organism, such as a multicellular animal. In some of the aspects described herein, a method or use can be said to occur “in vivo” when a unicellular organism, such as a bacterium, is used. The term "ex vivo" refers to methods and uses that are performed using a living cell with an intact membrane that is outside of the body of a multicellular animal or plant, e.g., explants, cultured cells, including primary cells and cell lines, transformed cell lines, and extracted tissue or cells, including blood cells, among others. The term “in vitro” refers to assays and methods that do not require the presence of a cell with an intact membrane, such as cellular extracts, and can refer to the introducing of a programmable synthetic biological circuit in a non-cellular system, such as a medium not comprising cells or cellular systems, such as cellular extracts. As used herein, an "isolated" molecule (e.g., nucleic acid or protein) or cell means it has been identified and separated and/or recovered from a component of its natural environment. An "isolated" nucleic acid molecule (such as, for example, an isolated promoter) is one which is separated from other nucleic acid molecules which are present in the natural source of the nucleic acid. For example, with regard to genomic DNA, the term "isolated" includes nucleic acid molecules which are separated from the chromosome with which the genomic DNA is naturally associated. Preferably, an "isolated" nucleic acid molecule is free of sequences which naturally flank the nucleic acid molecule in the genomic DNA of the organism from which the nucleic acid molecule is derived. As used herein, the term “minimal regulatory elements” is meant to refer to regulatory elements that are necessary for effective expression of a gene in a target cell and thus should be included in a transgene expression cassette. Such sequences could include, for example, promoter or enhancer sequences, a polylinker sequence facilitating the insertion of a DNA fragment within a plasmid vector, and sequences responsible for intron splicing and polyadenylation of mRNA transcripts. In a recent example of a gene therapy treatment for achromatopsia, the expression cassette included the minimal regulatory elements of a polyadenylation site, splicing signal sequences, and AAV inverted terminal repeats. See, e.g., Komaromy et al. (Hum Mol Genet.2010 Jul 1; 19(13): 2581–2593). As used herein, the term “minimize”, “reduce”, “decrease,” and/or “inhibit” (and like terms) generally refers to the act of reducing, either directly or indirectly, a concentration, level, function, activity, or behavior relative to the natural, expected, or average, or relative to a control condition. In certain embodiments, a “mutated gene” or “mutation” refers to an allelic form of a gene, which is capable of altering the phenotype of a subject having the mutated gene relative to a subject which does not have the mutated gene. The altered phenotype caused by a mutation can be corrected or compensated for by a gene therapy described herein. In certain embodiments, if a subject must be homozygous for this mutation to have an altered phenotype, the mutation is said to be recessive. In certain embodiments, if one copy of the mutated gene is sufficient to alter the phenotype of the subject, the mutation is said to be dominant. In certain embodiments, if a subject has one copy of the mutated gene and has a phenotype that is intermediate between that of a homozygous and that of a heterozygous subject (for that gene), the mutation is said to be co- dominant. In certain embodiments, the subject is heterozygous for the mutation. In certain embodiments, the subject is homozygous for the mutation. In some embodiments, “deficiency” of a gene, such as an achromatopsia (ACHM)- associated gene, means that the functional gene product (e.g., a protein in the case of a protein- encoding gene) is not substantially expressed. In some embodiments, gene deficiency includes a null phenotype for the gene. In some embodiments, a gene deficiency includes, without limitation, instances in which the gene has been deleted, instances in which the gene is not transcribed due to mutations in the transcription initiation sequence or the like, instances in the functional protein is not produced due to frameshift or codon mutations or the like, instances in which the activity of the expressed protein has been substantially eliminated due to amino acid mutations or the like, and instances in which protein translation is eliminated or substantially reduced. As used herein, a “nucleic acid” or a “nucleic acid molecule” is meant to refer to a molecule composed of chains of monomeric nucleotides, such as, for example, DNA molecules (e.g., cDNA or genomic DNA). In some embodiments, a nucleic acid may encode a nucleic acid sequence encoding an achromatopsia (ACHM)-associated gene, for example, a ATF6, CNGA3, CNGB3, GNAT2, PDE6C, and/or PDE6H gene. For example, a nucleic acid may encode, for example, a promoter, an achromatopsia (ACHM)-associated gene or portion thereof, or regulatory elements. An “achromatopsia (ACHM)-associated nucleic acid” refers to a nucleic acid that comprises the an achromatopsia (ACHM)-associated gene or a portion thereof, or a functional variant of the an achromatopsia (ACHM)-associated gene or a portion thereof. In some embodiments, a nucleic acid may encode, for example, a promoter, a cyclic nucleotide- gated channel beta 3 (CNGB3) gene or portion thereof, or regulatory elements. A nucleic acid molecule can be single-stranded or double-stranded. A “CNGB3 nucleic acid” refers to a nucleic acid that comprises the CNGB3 gene or a portion thereof, or a functional variant of the CNGB3 gene or a portion thereof. In some embodiments, a nucleic acid may encode, for example, a promoter, a cyclic nucleotide-gated channel alpha 3 (CNGA3) gene or portion thereof, or regulatory elements. A nucleic acid molecule can be single-stranded or double- stranded. A “CNGA3 nucleic acid” refers to a nucleic acid that comprises the CNGA3 gene or a portion thereof, or a functional variant of the CNGA3 gene or a portion thereof. A functional variant of a gene includes a variant of the gene with minor variations such as, for example, silent mutations, single nucleotide polymorphisms, missense mutations, and other mutations or deletions that do not significantly alter gene function. The asymmetric ends of DNA and RNA strands are called the 5′ (five prime) and 3′ (three prime) ends, with the 5' end having a terminal phosphate group and the 3' end a terminal hydroxyl group. The five prime (5’) end has the fifth carbon in the sugar-ring of the deoxyribose or ribose at its terminus. Nucleic acids are synthesized in vivo in the 5'- to 3'-direction, because the polymerase used to assemble new strands attaches each new nucleotide to the 3'-hydroxyl (- OH) group via a phosphodiester bond. The term “nucleic acid construct” as used herein refers to a nucleic acid molecule, either single- or double-stranded, which is isolated from a naturally occurring gene or which is modified to contain segments of nucleic acids in a manner that would not otherwise exist in nature or which is synthetic. The term nucleic acid construct is synonymous with the term “expression cassette” when the nucleic acid construct contains the control sequences required for expression of a coding sequence of the present disclosure. A DNA sequence that “encodes” a particular protein (including fragments and portions thereof) is a nucleic acid sequence that is transcribed into the particular RNA and/or protein. A DNA polynucleotide may encode an RNA (mRNA) that is translated into protein, or a DNA polynucleotide may encode an RNA that is not translated into protein (e.g., tRNA, rRNA, or a DNA-targeting RNA; also called "non-coding" RNA or "ncRNA"). As used herein, the terms “operatively linked” or “operably linked” or “coupled” can refer to a juxtaposition of genetic elements, wherein the elements are in a relationship permitting them to operate in an expected manner. For instance, a promoter can be operatively linked to a coding region if the promoter helps initiate transcription of the coding sequence. There may be intervening residues between the promoter and coding region so long as this functional relationship is maintained. As used herein, a “percent (%) sequence identity” with respect to a reference polypeptide or nucleic acid sequence is defined as the percentage of amino acid residues or nucleotides in a candidate sequence that are identical with the amino acid residues or nucleotides in the reference polypeptide or nucleic acid sequence, after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent sequence identity, and not considering any conservative substitutions as part of the sequence identity. Alignment for purposes of determining percent amino acid or nucleic acid sequence identity can be achieved in various ways that are within the skill in the art, for instance, using publicly available computer software programs, for example, those described in Current Protocols in Molecular Biology (Ausubel et al., eds., 1987), Supp.30, section 7.7.18, Table 7.7.1, and including BLAST, BLAST-2, ALIGN or Megalign (DNASTAR) software. An example of an alignment program is ALIGN Plus (Scientific and Educational Software, Pennsylvania). Those skilled in the art can determine appropriate parameters for measuring alignment, including any algorithms needed to achieve maximal alignment over the full length of the sequences being compared. For purposes herein, the % amino acid sequence identity of a given amino acid sequence A to, with, or against a given amino acid sequence B (which can alternatively be phrased as a given amino acid sequence A that has or comprises a certain % amino acid sequence identity to, with, or against a given amino acid sequence B) is calculated as follows: 100 times the fraction X/Y, where X is the number of amino acid residues scored as identical matches by the sequence alignment program in that program's alignment of A and B, and where Y is the total number of amino acid residues in B. It will be appreciated that where the length of amino acid sequence A is not equal to the length of amino acid sequence B, the % amino acid sequence identity of A to B will not equal the % amino acid sequence identity of B to A. For purposes herein, the % nucleic acid sequence identity of a given nucleic acid sequence C to, with, or against a given nucleic acid sequence D (which can alternatively be phrased as a given nucleic acid sequence C that has or comprises a certain % nucleic acid sequence identity to, with, or against a given nucleic acid sequence D) is calculated as follows: 100 times the fraction W/Z, where W is the number of nucleotides scored as identical matches by the sequence alignment program in that program's alignment of C and D, and where Z is the total number of nucleotides in D. It will be appreciated that where the length of nucleic acid sequence C is not equal to the length of nucleic acid sequence D, the % nucleic acid sequence identity of C to D will not equal the % nucleic acid sequence identity of D to C. As used herein, the term “pharmaceutical composition” or “composition” is meant to refer to a composition or agent described herein (e.g. a recombinant adeno-associated (rAAV) expression vector) , optionally mixed with at least one pharmaceutically acceptable chemical component, such as, though not limited to carriers, stabilizers, diluents, dispersing agents, suspending agents, thickening agents, excipients and the like. As used herein, the terms “polypeptide” and “protein” are used interchangeably to refer to a polymer of amino acid residues and are not limited to a minimum length. Such polymers of amino acid residues may contain natural or non-natural amino acid residues, and include, but are not limited to, peptides, oligopeptides, dimers, trimers, and multimers of amino acid residues. Both full-length proteins and fragments thereof are encompassed by the definition. The terms also include post-expression modifications of the polypeptide, for example, glycosylation, sialylation, acetylation, phosphorylation, and the like. Furthermore, for purposes of the present disclosure, a "polypeptide" refers to a protein which includes modifications, such as deletions, additions, and substitutions (generally conservative in nature) to the native sequence, as long as the protein maintains the desired activity. These modifications may be deliberate, as through site-directed mutagenesis, or may be accidental, such as through mutations of hosts which produce the proteins or errors due to PCR amplification. The asymmetric ends of DNA and RNA strands are called the 5′ (five prime) and 3′ (three prime) ends, with the 5' end having a terminal phosphate group and the 3' end a terminal hydroxyl group The five prime (5’) end has the fifth carbon in the sugar-ring of the deoxyribose or ribose at its terminus. Nucleic acids are synthesized in vivo in the 5'- to 3'-direction, because the polymerase used to assemble new strands attaches each new nucleotide to the 3'-hydroxyl (- OH) group via a phosphodiester bond. The term “5’-NTR” refers to a region of a gene that is not transcribed into RNA. This region is sometimes also known as the 5'-flanking region, which is generally before or upstream (i.e., toward the 5’ end of the DNA) of the transcription initiation site. The 5’-NTR contains the gene promoter and may also contain enhancers or other protein binding sites. As used herein, a “promoter” is meant to refer to a region of DNA that facilitates the transcription of a particular gene. As part of the process of transcription, the enzyme that synthesizes RNA, known as RNA polymerase, attaches to the DNA near a gene. Promoters contain specific DNA sequences and response elements that provide an initial binding site for RNA polymerase and for transcription factors that recruit RNA polymerase. The term “enhancer” as used herein refers to a cis-acting regulatory sequence (e.g., 50- 1,500 base pairs) that binds one or more proteins (e.g., activator proteins, or transcription factor) to increase transcriptional activation of a nucleic acid sequence. Enhancers can be positioned up to 1,000,000 base pars upstream of the gene start site or downstream of the gene start site that they regulate. A promoter can be said to drive expression or drive transcription of the nucleic acid sequence that it regulates. The phrases “operably linked,” “operatively positioned,” “operatively linked,” “under control,” and “under transcriptional control” indicate that a promoter is in a correct functional location and/or orientation in relation to a nucleic acid sequence it regulates to control transcriptional initiation and/or expression of that sequence. An “inverted promoter,” as used herein, refers to a promoter in which the nucleic acid sequence is in the reverse orientation, such that what was the coding strand is now the non-coding strand, and vice versa. Inverted promoter sequences can be used in various embodiments to regulate the state of a switch. In addition, in various embodiments, a promoter can be used in conjunction with an enhancer. A promoter can be one naturally associated with a gene or sequence, as can be obtained by isolating the 5' non-coding sequences located upstream of the coding segment and/or exon of a given gene or sequence. Such a promoter can be referred to as “endogenous.” Similarly, in some embodiments, an enhancer can be one naturally associated with a nucleic acid sequence, located either downstream or upstream of that sequence. In some embodiments, a coding nucleic acid segment is positioned under the control of a “recombinant promoter” or “heterologous promoter,” both of which refer to a promoter that is not normally associated with the encoded nucleic acid sequence it is operably linked to in its natural environment. A recombinant or heterologous enhancer refers to an enhancer not normally associated with a given nucleic acid sequence in its natural environment. Such promoters or enhancers can include promoters or enhancers of other genes; promoters or enhancers isolated from any other prokaryotic, viral, or eukaryotic cell; and synthetic promoters or enhancers that are not “naturally occurring,” i.e., comprise different elements of different transcriptional regulatory regions, and/or mutations that alter expression through methods of genetic engineering that are known in the art. As used herein, the term “recombinant” can refer to a biomolecule, e.g., a gene or protein, that (1) has been removed from its naturally occurring environment, (2) is not associated with all or a portion of a polynucleotide in which the gene is found in nature, (3) is operatively linked to a polynucleotide which it is not linked to in nature, or (4) does not occur in nature. The term “recombinant” can be used in reference to cloned DNA isolates, chemically synthesized polynucleotide analogs, or polynucleotide analogs that are biologically synthesized by heterologous systems, as well as proteins and/or mRNAs encoded by such nucleic acids. As used herein, a “subject” or “patient” or “individual” to be treated by the method of the invention is meant to refer to either a human or non-human animal. A “nonhuman animal” includes any vertebrate or invertebrate organism. The term “non-human animal” includes all vertebrates, e.g., mammals and non-mammals, such as non-human primates, mice, rabbits, sheep, dog, cat, horse, cow, chickens, amphibians, and reptiles. In a preferred embodiment, the subject is a human. A human subject can be of any age, gender, race or ethnic group, e.g., Caucasian (white), Asian, African, black, African American, African European, Hispanic, Middle eastern, etc. In some embodiments, the subject can be a patient or other subject in a clinical setting. In some embodiments, the subject is already undergoing treatment. In some embodiments, the subject is a neonate, infant, child, adolescent, or adult. As used herein the term “therapeutic effect” refers to a consequence of treatment, the results of which are judged to be desirable and beneficial. A therapeutic effect can include, directly or indirectly, the arrest, reduction, or elimination of a disease manifestation. A therapeutic effect can also include, directly or indirectly, the arrest reduction or elimination of the progression of a disease manifestation. For any therapeutic agent described herein therapeutically effective amount may be initially determined from preliminary in vitro studies and/or animal models. A therapeutically effective dose may also be determined from human data. The applied dose may be adjusted based on the relative bioavailability and potency of the administered compound. Adjusting the dose to achieve maximal efficacy based on the methods described above and other well-known methods is within the capabilities of the ordinarily skilled artisan. General principles for determining therapeutic effectiveness, which may be found in Chapter 1 of Goodman and Gilman’s The Pharmacological Basis of Therapeutics, 10th Edition, McGraw-Hill (New York) (2001), incorporated herein by reference, are summarized below. As used herein, the term “central retina”" refers to the outer macula and/or inner macula and/or the fovea. The term "central retina cell types" as used herein refers to cell types of the central retina, such as, for example, retinal pigment epithelium (RPE) and photoreceptor cells. The retina contains three kinds of photoreceptors: rod cells, cone cells, and photoreceptive ganglion cells. Cone cells are of three types: S-cone cells, M-cone cells, and L- cone cells. S-cone cells respond most strongly to short wavelength light (peak near 420-440 nm) and are also known as blue cones. M-cone cells respond most strongly to medium wavelength light (peak near 534-545 nm) and are also known as green cones. L-cone cells respond most strongly to light of long wavelengths (peak near 564–580 nm) and are also known as red cones. The difference in the signals received from the three cone types allows the brain to perceive all possible colors. As used herein, the term “macula” refers to a region of the central retina in primates that contains a higher relative concentration of photoreceptor cells, specifically rods and cones, compared to the peripheral retina. The term "outer macula" as used herein may also be referred to as the "peripheral macula". The term "inner macula" as used herein may also be referred to as the "central macula". As used herein, the term “fovea” is meant to refer to a small region in the central retina of primates of approximately equal to or less than 1.5 mm in diameter that contains a higher relative concentration of photoreceptor cells, specifically cones, when compared to the peripheral retina and the macula. As used herein, the term “subretinal space” refers to the location in the retina between the photoreceptor cells and the retinal pigment epithelium cells. The subretinal space may be a potential space, such as prior to any subretinal injection of fluid. The subretinal space may also contain a fluid that is injected into the potential space. In this case, the fluid is “in contact with the subretinal space.” Cells that are “in contact with the subretinal space” include the cells that border the subretinal space, such as RPE and photoreceptor cells. As used herein, the term “transgene” is meant to refer to a polynucleotide that is introduced into a cell and is capable of being transcribed into RNA and optionally, translated and/or expressed under appropriate conditions. In aspects, it confers a desired property to a cell into which it was introduced, or otherwise leads to a desired therapeutic or diagnostic outcome. A “transgene expression cassette” or “expression cassette” are used interchangeably and refer to a linear stretch of nucleic acids that includes a transgene that is operably linked to one or more promoters or other regulatory sequences sufficient to direct transcription of the transgene, but which does not comprise capsid-encoding sequences, other vector sequences or inverted terminal repeat regions. An expression cassette may additionally comprise one or more cis- acting sequences (e.g., promoters, enhancers, or repressors), one or more introns, and one or more post-transcriptional regulatory elements. A transgene expression cassette comprises the gene sequences that a nucleic acid vector is to deliver to target cells. These sequences include the gene of interest (e.g., achromatopsia (ACHM)-associated nucleic acids or variants thereof), one or more promoters, and minimal regulatory elements. As used herein, the term “treatment” or “treating” a disease or disorder (such as, for example, achromatopsia (ACHM)) is meant to refer to alleviation of one or more signs or symptoms of the disease or disorder, diminishment of extent of disease or disorder, stabilized (e.g., not worsening) state of disease or disorder, preventing spread of disease or disorder, delay or slowing of disease or disorder progression, amelioration or palliation of the disease or disorder state, and remission (whether partial or total), whether detectable or undetectable. “Treatment” can also refer to prolonging survival as compared to expected survival if not receiving treatment. “Treating” a disease (such as, for example, achromatopsia) may also refer to alleviating, preventing, or delaying the occurrence of at least one sign or symptom of the disease. As used herein, the term “vector” refers to a recombinant plasmid or virus that comprises a nucleic acid to be delivered into a host cell, either in vitro or in vivo. As used herein, the term “expression vector” refers to a vector that directs expression of an RNA or polypeptide from sequences linked to transcriptional regulatory sequences on the vector. The sequences expressed will often, but not necessarily, be heterologous to the cell. An expression vector may comprise additional elements, for example, the expression vector may have two replication systems, thus allowing it to be maintained in two organisms, for example in human cells for expression and in a prokaryotic host for cloning and amplification. The term "expression" refers to the cellular processes involved in producing RNA and proteins and as appropriate, secreting proteins, including where applicable, but not limited to, for example, transcription, transcript processing, translation and protein folding, modification and processing. “Expression products” include RNA transcribed from a gene, and polypeptides obtained by translation of mRNA transcribed from a gene. The term “gene” means the nucleic acid sequence which is transcribed (DNA) to RNA in vitro or in vivo when operably linked to appropriate regulatory sequences. The gene may or may not include regions preceding and following the coding region, e.g., 5’ untranslated (5’UTR) or "leader" sequences and 3’ UTR or “trailer” sequences, as well as intervening sequences (introns) between individual coding segments (exons). As used herein, a “recombinant viral vector” refers to a recombinant polynucleotide vector comprising one or more heterologous sequences (i.e., nucleic acid sequence not of viral origin). In the case of recombinant AAV vectors, the recombinant nucleic acid is flanked by at least one inverted terminal repeat sequence (ITR). In some embodiments, the recombinant nucleic acid is flanked by two ITRs. As used herein, a “recombinant AAV vector (rAAV vector)” refers to a polynucleotide vector comprising one or more heterologous sequences (i.e., nucleic acid sequence not of AAV origin) that are flanked by at least one AAV inverted terminal repeat sequence (ITR). Such rAAV vectors can be replicated and packaged into infectious viral particles when present in a host cell that has been infected with a suitable helper virus (or that is expressing suitable helper functions) and that is expressing AAV rep and cap gene products (i.e. AAV Rep and Cap proteins). When a rAAV vector is incorporated into a larger polynucleotide (e.g., in a chromosome or in another vector such as a plasmid used for cloning or transfection), then the rAAV vector may be referred to as a "pro-vector" which can be "rescued" by replication and encapsidation in the presence of AAV packaging functions and suitable helper functions. A rAAV vector can be in any of a number of forms, including, but not limited to, plasmids, linear artificial chromosomes, complexed with lipids, encapsulated within liposomes, and encapsidated in a viral particle, e.g., an AAV particle. A rAAV vector can be packaged into an AAV virus capsid to generate a "recombinant adeno-associated viral particle (rAAV particle)". As used herein, a “rAAV virus” or “rAAV viral particle” refers to a viral particle composed of at least one AAV capsid protein and an encapsidated rAAV vector genome. As used herein the term “comprising” or “comprises” is used in reference to compositions, methods, and respective component(s) thereof, that are essential to the method or composition, yet open to the inclusion of unspecified elements, whether essential or not. As used herein the term “consisting essentially of” refers to those elements required for a given embodiment. The term permits the presence of elements that do not materially affect the basic and novel or functional characteristic(s) of that embodiment. The use of “comprising” indicates inclusion rather than limitation. The term “consisting of” refers to compositions, methods, and respective components thereof as described herein, which are exclusive of any element not recited in that description of the embodiment. As used herein the term “consisting essentially of” refers to those elements required for a given embodiment. The term permits the presence of additional elements that do not materially affect the basic and novel or functional characteristic(s) of that embodiment of the invention. As used herein, the terms “identify” or “select” refer to a choice in preference to another. In other words, to identify a subject or select a subject is to perform the active step of picking out that particular subject from a group and confirming the identity of the subject by name or other distinguishing feature With respect to the instant invention it is understood that in certain embodiments, identifying a subject or selecting a subject based on an analysis of the subject’s retinal structure and/or function, can include any of a number of acts including, but not limited to, performing a test and observing a result that is indicative of a subject having a retinal structure and/or function; reviewing a test result of a subject and identifying the subject as having a specific retinal structure and/or function; reviewing documentation on a subject stating that the subject has a specific retinal structure and/or function and identifying the subject as the one discussed in the documentation by confirming the identity of the subject e.g., by an identification card, hospital bracelet, asking the subject for his/her name and/ or other personal information to confirm the subjects identity. In certain embodiments, identifying a subject or selecting a subject may comprise selecting the subject if a predetermined pattern of fundus autofluorescence (FAF) is present in an eye of the subject at baseline. In certain embodiments, identifying a subject or selecting a subject may comprise classifying the pattern of fundus autofluorescence (FAF) in the eye of the subject as comprising central hypoautofluorescence (grade 0), normal autofluorescence (grade 1), or mild or strong hyperautofluorescence (grade 2). In certain embodiments, (a) a pattern of FAF comprising central hypoautofluorescence (grade 0) identifies a subject that is less likely to be a visual field responder; (b) a pattern of FAF comprising normal autofluorescence (grade 1) identifies a subject that is less likely to be a visual field responder; and/or (c) a pattern of FAF comprising mild or strong hyperautofluorescence (grade 2) identifies a subject that is more likely to be a visual field responder. In certain embodiments, the predetermined pattern of fundus autofluorescence (FAF) may be mild or strong hyperautofluorescence (grade 2). In certain embodiments, the predetermined pattern of fundus autofluorescence (FAF) in the eye of the subject is obtained prior to or at the time of administration of the therapy suitable for treating achromatopsia (ACHM). In certain embodiments, identifying a subject or selecting a subject may comprise monitoring the pattern of fundus autofluorescence (FAF) in the eye of the subject for a period of time after administration of the therapy suitable for treating achromatopsia (ACHM). In certain embodiments, identifying a subject or selecting a subject may comprise selecting the subject if a predetermined optical coherence tomography (OCT) central outer retina morphology is present in an eye of the subject at baseline. In certain embodiments, identifying a subject or selecting a subject may comprise classifying the optical coherence tomography (OCT) central outer retina morphology in the eye of the subject as comprising central absence of ellipsoid zone (EZ) line disturbance (grade 0), the presence of EZ line disturbance (grade 1), or the presence of empty optical space (grade 2). In certain embodiments, (a) an OCT central outer retina morphology comprising the central absence of ellipsoid zone (EZ) line disturbance (grade 0) identifies a subject that is more likely to be a visual field responder; (b) an OCT central outer retina morphology comprising the presence of EZ line disturbance (grade 1) identifies a subject that is more likely to be a visual field responder; and/or (c) an OCT central outer retina morphology comprising the presence of empty optical space (grade 2) identifies a subject that is less likely to be a visual field responder. In certain embodiments, the predetermined optical coherence tomography (OCT) central outer retina morphology is central absence of ellipsoid zone (EZ) line disturbance (grade 0) or presence of EZ line disturbance (grade 1). With respect to the instant invention, it is understood that, in certain embodiments, identifying a subject or selecting a subject as having one or more alterations or mutations in one or more genes of interest, having a wild-type gene, or having a change in the expression level of a protein, can include any of a number of acts including, but not limited to, performing a test and observing a result that is indicative of a subject having a specific mutation; reviewing a test result of a subject and identifying the subject as having a specific mutation; reviewing documentation on a subject stating that the subject has a specific mutation and identifying the subject as the one discussed in the documentation by confirming the identity of the subject e.g., by an identification card, hospital bracelet, asking the subject for his/her name and/ or other personal information to confirm the subjects identity. As used herein, “likelihood” and “likely” is a measurement of how probable an event is to occur. It may be used interchangeably with “probability”. Likelihood refers to a probability that is more than speculation, but less than certainty. Thus, an event is likely if a reasonable person using common sense, training or experience concludes that, given the circumstances, an event is probable. In some embodiments, once likelihood has been ascertained, the subject may be treated (or treatment continued, or treatment proceed with a dosage increase) or the subject may not be treated (or treatment discontinued, or treatment proceed with a lowered dose). The term “expression” is used herein to mean the process by which a polypeptide is produced from DNA. The process involves the transcription of the gene into mRNA and the translation of this mRNA into a polypeptide. Depending on the context in which used, “expression” may refer to the production of RNA, or protein, or both. The terms “level of expression of a gene” or “gene expression level” refer to the level of mRNA, as well as pre-mRNA nascent transcript(s), transcript processing intermediates, mature mRNA(s) and degradation products, or the level of protein, encoded by the gene in the cell. As used herein, “level of activity” is understood as the amount of protein activity as determined by a quantitative, semi-quantitative, or qualitative assay. Mutations, alterations and protein expression levels are preferably detected in a subject sample. The term “sample” as used herein refers to a collection of similar fluids, cells, or tissues isolated from a subject. The term “sample” includes any body fluid (e.g., urine, serum, blood fluids, lymph, gynecological fluids, cystic fluid, ascetic fluid, ocular fluids, and fluids collected by bronchial lavage and/or peritoneal rinsing), ascites, tissue samples or a cell from a subject. Other subject samples include tear drops, serum, cerebrospinal fluid, feces, sputum, and cell extracts. In an embodiment, the sample is removed from the subject. In a particular embodiment, the sample is blood fluids. In a particular embodiment, the sample is urine or serum. In a particular embodiment, the sample is ocular fluids. In an embodiment, the sample comprises cells. In another embodiment, the sample does not comprise cells. II. Nucleic Acids The present disclosure provides promoters, expression cassettes, vectors, kits, and methods that can be used in the treatment of diseases and disorders associated with a deficiency of an achromatopsia (ACHM)-associated gene. In particular, the disclosure provides nucleic acids that can be used in the treatment of retinal diseases or disorders, including, without limitation, achromatopsia (ACHM). In certain embodiments, the promoters, achromatopsia (ACHM)-associated nucleic acids (e.g., CNGB3 and/or CNGA3 nucleic acids), regulatory elements, and expression cassettes, and vectors of the disclosure may be used according to any of the methods describes herein, e.g., for treating or selecting a subject for treatment of a retinal disease or disorder, including, without limitation, achromatopsia (ACHM), based on an analysis of the subject’s retinal structure and/or function. Certain aspects of the disclosure relate to selecting a subject for treatment with a gene therapy suitable for treating achromatopsia (ACHM), for example, based on an analysis of the subject’s retinal structure and/or function. Certain aspects of the disclosure relate to selecting a subject having a mutation in an achromatopsia (ACHM)-associated gene selected from the group consisting of ATF6, CNGA3, CNGB3, GNAT2, PDE6C, and PDE6H gene for treatment with a gene therapy suitable for treating achromatopsia (ACHM), for example, based on an analysis of the subject’s retinal structure and/or function. Certain aspects of the disclosure relate to selecting a subject having a mutation in a cyclic nucleotide-gated channel beta 3 (CNGB3) gene for treatment with a gene therapy comprising a nucleic acid sequence encoding CNGB3, for example, based on an analysis of the subject’s retinal structure and/or function. Certain aspects of the disclosure relate to selecting a subject having a mutation in a cyclic nucleotide-gated channel alpha 3 (CNGA3) gene for treatment with a gene therapy comprising a nucleic acid sequence encoding CNGA3, for example, based on an analysis of the subject’s retinal structure and/or function. According to some aspects, the disclosure relates to delivering a heterologous nucleic acid to a subject comprising administering a gene therapy to the subject. Certain aspects of the disclosure relate to delivering a heterologous nucleic acid to an eye of a subject comprising administering a gene therapy comprising a nucleic acid sequence encoding CNGB3 and/or CNGA3 to the eye of the subject. Certain aspects of the disclosure relate to delivering a heterologous nucleic acid to an eye of a subject comprising administering a recombinant adeno-associated virus (rAAV) vector to the eye of the subject. According to some aspects, the disclosure provides methods of treating a disease or disorder associated with a deficiency of a CNGB3 and/or CNGA3 gene comprising delivery of a composition comprising rAAV vectors described herein to the subject, wherein the rAAV vector comprises a heterologous nucleic acid (e.g., a nucleic acid encoding CNGB3) and further comprising two AAV terminal repeats. According to some embodiments, the heterologous nucleic acid is operably linked to a promoter. A “CNGB3 nucleic acid” refers to a nucleic acid that comprises the CNGB3 gene or a portion thereof, or a functional variant of the CNGB3 gene or a portion thereof. A functional variant of a gene includes a variant of the gene with minor variations such as, for example, silent mutations, single nucleotide polymorphisms, missense mutations, and other mutations or deletions that do not significantly alter gene function. According to some embodiments, a nucleic acid of the present invention encodes a CNGB3 protein. According to some embodiments, the expressed CNGB3 protein is functional for the treatment of a disease or disorder associated with a deficiency of a cyclic nucleotide- gated channel beta 3 (CNGB3) gene. In some embodiments, the expressed CNGB3 protein is functional for the treatment of a retinal disease or disorder, for example, without limitation, achromatopsia (ACHM). In some embodiments, expressed CNGB3 protein does not cause an immune system reaction. According to some embodiments, the CNGB3 nucleic acid comprises the sequence of hCNGB3co (SEQ ID NO: 1), or a portion thereof. SEQ ID NO: 1

According to some embodiments, the CNGB3 nucleic acid comprises the nucleic acid sequence of SEQ ID NO: 1. According to some embodiments, the CNGB3 nucleic acid consists of the nucleic acid sequence of SEQ ID NO: 1. According to some embodiments, the nucleic acid is at least 85% identical to SEQ ID NO: 1. According to some embodiments, the nucleic acid is at least 90% identical to SEQ ID NO: 1 According to some embodiments, the nucleic acid is at least 95% identical to SEQ ID NO: 1. According to some embodiments, the nucleic acid is at least 99% identical to SEQ ID NO: 1. According to some embodiments, the CNGB3 nucleic acid is codon optimized for mammalian expression. According to some embodiments, the CNGA3 nucleic acid comprises the sequence of hCNGA3co (SEQ ID NO: 150), or a portion thereof. SEQ ID NO: 150

According to some embodiments, the CNGA3 nucleic acid comprises the nucleic acid sequence of SEQ ID NO: 150. According to some embodiments, the CNGA3 nucleic acid consists of the nucleic acid sequence of SEQ ID NO: 150. According to some embodiments, the nucleic acid is at least 85% identical to SEQ ID NO: 150. According to some embodiments, the nucleic acid is at least 90% identical to SEQ ID NO: 150 According to some embodiments, the nucleic acid is at least 95% identical to SEQ ID NO: 150. According to some embodiments, the nucleic acid is at least 99% identical to SEQ ID NO: 150. According to some embodiments, the CNGA3 nucleic acid is codon optimized for mammalian expression. Making the nucleic acids of the invention A nucleic acid molecule (including, for example, an achromatopsia (ACHM)-associated nucleic acid, such as a CNGB3 and/or CNGA3 nucleic acids) of the present invention can be isolated using standard molecular biology techniques. Using all or a portion of a nucleic acid sequence of interest as a hybridization probe, nucleic acid molecules can be isolated using standard hybridization and cloning techniques (e.g., as described in Sambrook, J., Fritsh, E. F., and Maniatis, T. Molecular Cloning. A Laboratory Manual.2nd, ed., Cold Spring Harbor Laboratory, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1989). A nucleic acid molecule for use in the methods of the invention can also be isolated by the polymerase chain reaction (PCR) using synthetic oligonucleotide primers designed based upon the sequence of a nucleic acid molecule of interest. A nucleic acid molecule used in the methods of the invention can be amplified using cDNA, mRNA or, alternatively, genomic DNA as a template and appropriate oligonucleotide primers according to standard PCR amplification techniques. Furthermore, oligonucleotides corresponding to nucleotide sequences of interest can also be chemically synthesized using standard techniques. Numerous methods of chemically synthesizing polydeoxynucleotides are known, including solid-phase synthesis which has been automated in commercially available DNA synthesizers (See e.g., Itakura et al. U.S. Patent No. 4,598,049; Caruthers et al. U.S. Patent No.4,458,066; and Itakura U.S. Patent Nos.4,401,796 and 4,373,071, incorporated by reference herein). Automated methods for designing synthetic oligonucleotides are available. See e.g., Hoover, D.M. & Lubowski, 2002. J. Nucleic Acids Research, 30(10): e43. Many embodiments of the invention involve an achromatopsia (ACHM)-associated nucleic acid. Some aspects and embodiments of the invention involve other nucleic acids, such as isolated promoters or regulatory elements. A nucleic acid may be, for example, a cDNA or a chemically synthesized nucleic acid. A cDNA can be obtained, for example, by amplification using the polymerase chain reaction (PCR) or by screening an appropriate cDNA library. Alternatively, a nucleic acid may be chemically synthesized. III. PROMOTERS, EXPRESSION CASSETTES AND VECTORS The promoters, achromatopsia (ACHM)-associated nucleic acids (e.g., CNGB3 and/or CNGA3 nucleic acids), regulatory elements, and expression cassettes, and vectors of the disclosure may be produced using methods known in the art. The methods described below are provided as non-limiting examples of such methods. Furthermore, the promoters, achromatopsia (ACHM)-associated nucleic acids (e.g., CNGB3 and/or CNGA3 nucleic acids), regulatory elements, and expression cassettes, and vectors of the disclosure may be used according to any of the methods describes herein, e.g., for treating or selecting a subject for treatment of a retinal disease or disorder, including, without limitation, achromatopsia (ACHM), for example, based on an analysis of the subject’s retinal structure and/or function. Promoters Exemplary promoters include, but are not limited to, the cytomegalovirus (CMV) immediate early promoter, the RSV LTR, the MoMLV LTR, the phosphoglycerate kinase-1 (PGK) promoter, a simian virus 40 (SV40) promoter and a CK6 promoter, a transthyretin promoter (TTR), a TK promoter, a tetracycline responsive promoter (TRE), an HBV promoter, an hAAT promoter, a LSP promoter, chimeric liver-specific promoters (LSPs), the E2F promoter, the telomerase (hTERT) promoter; the chicken beta-actin promoter, the small version of the hybrid CMV-chicken beta-actin promoter (smCBA) (Pang et al., Invest Ophthalmol Vis Sci.2008 Oct; 49(10):4278-83); the a cytomegalovirus enhancer linked to a chicken beta-actin (CBA) promoter; the cytomegalovirus enhancer/chicken beta-actin/Rabbit beta-globin promoter (CAG promoter; Niwa et al., Gene, 1991, 108(2):193-9) and the elongation factor 1-alpha promoter (EF1-alpha) promoter (Kim et al., Gene, 1990, 91(2):217-23 and Guo et al., Gene Ther., 1996, 3(9):802-10). In some embodiments, the promoter comprises the chicken beta-actin promoter. According to some embodiments, the promoter comprises the small version of the hybrid CMV-chicken beta-actin promoter (smCBA) The promoter can be a constitutive inducible or repressible promoter. In some embodiments, the promoter is capable of expressing the heterologous nucleic acid in a cell of the eye. In some embodiments, the promoter is capable of expressing the heterologous nucleic acid in photoreceptor cells or RPE. In some embodiments, the promoter is capable of expressing the heterologous nucleic acid in a multitude of retinal cells. In other embodiments, the promoter may comprise segments of a achromatopsia (ACHM)-associated gene, for example, a human achromatopsia (ACHM)- associated gene. In other embodiments, the achromatopsia (ACHM)-associated gene is a achromatopsia (ACHM)-associated gene from a non-human animal. In other embodiments, the promoter may comprise segments of a CNGB3 gene, for example, a human CNGB3 (hCNGB3) gene. In other embodiments, the CNGB3 gene is a CNGB3 gene from a non-human animal. In other embodiments, the promoter may comprise segments of a CNGA3 gene, for example, a human CNGA3 (hCNGA3) gene. In other embodiments, the CNGA3 gene is a CNGA3 gene from a non-human animal. In some embodiments, the promoter is capable of promoting expression of a transgene in S-cone, M-cone, and L-cone cells. A “transgene” refers to a segment of DNA containing a gene sequence that has been isolated from one organism and is introduced into a different organism. For example, to treat an individual who has achromatopsia caused by a mutation of an achromatopsia (ACHM)-associated gene, a wild-type (i.e., non-mutated, or functional variant) achromatopsia (ACHM)-associated gene may be administered using an appropriate vector. The wild-type gene is referred to as a “transgene.” In preferred embodiments, the transgene is a wild-type version of a gene that encodes a protein that is normally expressed in cone cells of the retina. In one such embodiment, the transgene is derived from a human gene. In a first specific embodiment, the promoter is capable of promoting expression of an achromatopsia (ACHM)- associated nucleic acid in S-cone, M-cone, and/or L-cone cells. For example, to treat an individual who has achromatopsia caused by a mutation of the human CNGB3 gene, a wild-type (i.e., non-mutated, or functional variant) human CNGB3 gene may be administered using an appropriate vector. The wild-type gene is referred to as a “transgene.” In preferred embodiments, the transgene is a wild-type version of a gene that encodes a protein that is normally expressed in cone cells of the retina. In one such embodiment, the transgene is derived from a human gene. In a first specific embodiment, the promoter is capable of promoting expression of a CNGB3 nucleic acid in S-cone, M-cone, and/or L-cone cells. In these specific embodiments, the CNGB3, is preferably human CNGB3. (See, e.g., WO2014186160, incorporated by reference herein). For example, to treat an individual who has achromatopsia caused by a mutation of the human CNGA3 gene, a wild-type (i.e., non-mutated, or functional variant) human CNGA3 gene may be administered using an appropriate vector. The wild-type gene is referred to as a “transgene.” In preferred embodiments, the transgene is a wild-type version of a gene that encodes a protein that is normally expressed in cone cells of the retina. In one such embodiment, the transgene is derived from a human gene. In a first specific embodiment, the promoter is capable of promoting expression of a CNGA3 nucleic acid in S-cone, M-cone, and/or L-cone cells. In these specific embodiments, the CNGA3, is preferably human CNGA3. (See, e.g., WO2014186160, incorporated by reference herein). In another aspect, the present invention provides promoters that are shortened versions of the PR2.1 promoter (See, e.g., WO2014186160, incorporated by reference herein), which may optionally include additional enhancer sequences. Such promoters have the advantage that they fit better within the packaging capacity of AAV vectors and therefore provide advantages such as, for example, improved yields, a lower empty-to-full particle ratio, and higher infectivity of the vector. In some embodiments, these promoters are created by truncating the 5’-end of PR2.1 while leaving the 500bp core promoter and the 600bp locus control region (LCR) intact. In some such embodiments, the lengths of the truncations are selected from the group consisting of approximately 300bp, 500bp, and 1,100 bp (see, e.g., PR1.7, PR1.5, and PR1.1, respectively, as described in Example 1 of WO2014186160). In one particular embodiment, the present invention provides a PR1.7 promoter (SEQ ID NO: 2). SEQ ID NO: 2

Expression Cassettes In another aspect, the present invention provides a transgene expression cassette that includes (a) a promoter; (b) a nucleic acid comprising a CNGB3 nucleic acid as described herein; and (c) minimal regulatory elements. A promoter of the invention includes the promoters discussed supra. According to some embodiments, the promoter a PR1.7 promoter (SEQ ID NO: 2). According to some embodiments, a nucleic acid of the present invention encodes an achromatopsia (ACHM)-associated gene. According to some embodiments, a nucleic acid of the present invention encodes a CNGB3 gene. According to some embodiments, a nucleic acid of the present invention encodes a CNGA3 gene. A “CNGB3 nucleic acid” refers to a nucleic acid that comprises the CNGB3 gene or a portion thereof, or a functional variant of the CNGB3 gene or a portion thereof. Similarly, a “CNGA3 nucleic acid” refers to a nucleic acid that comprises the CNGA3 gene or a portion thereof, or a functional variant of the CNGA3 gene or a portion thereof. A functional variant of a gene includes a variant of the gene with minor variations such as, for example, silent mutations, single nucleotide polymorphisms, missense mutations, and other mutations or deletions that do not significantly alter gene function. In certain embodiments, the nucleic acid is a human nucleic acid (i.e., a nucleic acid that is derived from a human CNGB3 gene). In other embodiments, the nucleic acid is a non- human nucleic acid (i.e., a nucleic acid that is derived from a non-human CNGB3 gene). According to some embodiments, the CNGB3 nucleic acid comprises the sequence of hCNGB3co (SEQ ID NO: 1), or a portion thereof. In some embodiments, the nucleic acid consists of SEQ ID NO: 1. According to some embodiments, the nucleic acid is at least 85% identical to SEQ ID NO: 1. According to some embodiments, the nucleic acid is at least 90% identical to SEQ ID NO: 1. According to some embodiments, the nucleic acid is at least 95% identical to SEQ ID NO: 1. According to some embodiments, the nucleic acid is at least 99% identical to SEQ ID NO: 1. In certain embodiments, the nucleic acid is a human nucleic acid (i.e., a nucleic acid that is derived from a human CNGA3 gene). In other embodiments, the nucleic acid is a non- human nucleic acid (i.e., a nucleic acid that is derived from a non-human CNGA3 gene). According to some embodiments, the CNGA3 nucleic acid comprises the sequence of hCNGA3co (SEQ ID NO: 150), or a portion thereof. In some embodiments, the nucleic acid consists of SEQ ID NO: 150. According to some embodiments, the nucleic acid is at least 85% identical to SEQ ID NO: 150. According to some embodiments, the nucleic acid is at least 90% identical to SEQ ID NO: 150. According to some embodiments, the nucleic acid is at least 95% identical to SEQ ID NO: 150. According to some embodiments, the nucleic acid is at least 99% identical to SEQ ID NO: 150. According to some embodiments, the recombinant nucleic acid is flanked by at least two ITRs. According to some embodiments, the ITRs comprises the sequences of SEQ ID NO: 3 and SEQ ID NO: 4. SEQ ID NO: 3

According to some embodiments, the construct comprises a CNGB3 nucleic acid comprising the sequence of hCNGB3co (SEQ ID NO: 1), or a portion thereof, and inverted terminal repeats (TR-PR1.7-hCNGB3co-TR). According to some embodiments, TR-PR1.7-hCNGB3co-TR comprises the nucleic acid sequence of SEQ ID NO: 100. SEQ ID NO: 100

According to some embodiments, TR-PR1.7-hCNGB3co-TR consists of the nucleic acid sequence of SEQ ID NO: 100. According to some embodiments, the nucleic acid is at least 85% identical to SEQ ID NO: 100. According to some embodiments, the nucleic acid is at least 90% identical to SEQ ID NO: 100. According to some embodiments, the nucleic acid is at least 95% identical to SEQ ID NO: 100. According to some embodiments, the nucleic acid is at least 99% identical to SEQ ID NO: 100. According to some embodiments, the construct comprises a CNGA3 nucleic acid comprising the sequence of hCNGA3co (SEQ ID NO: 150), or a portion thereof, and inverted terminal repeats (TR-PR1.7-hCNGA3co-TR). According to some embodiments, TR-PR1.7-hCNGA3co-TR comprises the nucleic acid sequence of SEQ ID NO: 200. SEQ ID NO: 200

According to some embodiments, TR-PR1.7-hCNGA3co-TR consists of the nucleic acid sequence of SEQ ID NO: 200. According to some embodiments, the nucleic acid is at least 85% identical to SEQ ID NO: 200. According to some embodiments, the nucleic acid is at least 90% identical to SEQ ID NO: 200. According to some embodiments, the nucleic acid is at least 95% identical to SEQ ID NO: 200. According to some embodiments, the nucleic acid is at least 99% identical to SEQ ID NO: 200. “Minimal regulatory elements” are regulatory elements that are necessary for effective expression of a gene in a target cell Such regulatory elements could include for example promoter or enhancer sequences, a polylinker sequence facilitating the insertion of a DNA fragment within a plasmid vector, and sequences responsible for intron splicing and polyadenylation of mRNA transcripts. In a recent example of a gene therapy treatment for achromatopsia, the expression cassette included the minimal regulatory elements of a polyadenylation site, splicing signal sequences, and AAV inverted terminal repeats. See, e.g., Komaromy et al.. The expression cassettes of the invention may also optionally include additional regulatory elements that are not necessary for effective incorporation of a gene into a target cell. According to some embodiments, the construct comprises a SV(40) polyA. Vectors The present invention also provides vectors that include any one of the expression cassettes discussed in the preceding section. In some embodiments, the vector is an oligonucleotide that comprises the sequences of the expression cassette. In specific embodiments, delivery of the oligonucleotide may be accomplished by in vivo electroporation (see, e.g., Chalberg, TW, et al. Investigative Ophthalmology &Visual Science, 46, 2140–2146 (2005) (hereinafter Chalberg et al., 2005)) or electron avalanche transfection (see, e.g., Chalberg, TW, et al. Investigative Ophthalmology &Visual Science, 47, 4083–4090 (2006) (hereinafter Chalberg et al., 2006)). In further embodiments, the vector is a DNA-compacting peptide (see, e.g., Farjo, R, et al. PLoS ONE, 1, e38 (2006) (hereinafter Farjo et al., 2006), where CK30, a peptide containing a cysteine residue coupled to polyethylene glycol followed by 30 lysines, was used for gene transfer to photoreceptors), a peptide with cell penetrating properties (see Johnson, LN, et al., Cell-penetrating peptide for enhanced delivery of nucleic acids and drugs to ocular tissues including retina and cornea. Molecular Therapy, 16(1), 107–114 (2007) (hereinafter Johnson et al., 2007), Barnett, EM, et al. Investigative Ophthalmology & Visual Science, 47, 2589–2595 (2006) (hereinafter Barnett et al., 2006), Cashman, SM, et al. Molecular Therapy, 8, 130–142 (2003) (hereinafter Cashman et al., 2003), Schorderet, DF, et al. Clinical and Experimental Ophthalmology, 33, 628–635 (2005) (hereinafter Schorderet et al., 2005), Kretz, A, et al.. Molecular Therapy, 7, 659–669 (2003) (hereinafter Kretz et al.2003) for examples of peptide delivery to ocular cells), or a DNA-encapsulating lipoplex, polyplex, liposome, or immunoliposome (see e.g., Zhang, Y, et al. Molecular Vision, 9, 465–472 (2003) (hereinafter Zhang et al.2003), Zhu, C, et al. Investigative Ophthalmology & Visual Science, 43, 3075–3080 (2002) (hereinafter Zhu et al.2002), Zhu, C., et al. Journal of Gene Medicine, 6, 906–912. (2004) (hereinafter Zhu et al.2004)). In preferred embodiments, the vector is a viral vector, such as a vector derived from an adeno-associated virus, an adenovirus, a retrovirus, a lentivirus, a vaccinia/poxvirus, or a herpesvirus (e.g., herpes simplex virus (HSV)). See e.g., Howarth, JL et al., Using viral vectors as gene transfer tools. Cell Biol Toxicol 26:1-10 (2010). In the most preferred embodiments, the vector is an adeno-associated viral (AAV) vector. Multiple serotypes of adeno-associated virus (AAV), including 12 human serotypes (AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10, AAV11, and AAV12) and more than 100 serotypes from nonhuman primates have now been identified. Howarth JL et al., 2010. In embodiments of the present invention wherein the vector is an AAV vector, the serotype of the inverted terminal repeats (ITRs) of the AAV vector may be selected from any known human or nonhuman AAV serotype. In preferred embodiments, the serotype of the AAV ITRs of the AAV vector is selected from the group consisting of AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10, AAV11, and AAV12. Moreover, in embodiments of the present invention wherein the vector is an AAV vector, the serotype of the capsid sequence of the AAV vector may be selected from any known human or animal AAV serotype. In some embodiments, the serotype of the capsid sequence of the AAV vector is selected from the group consisting of AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10, AAV11, and AAV12. In preferred embodiments, the serotype of the capsid sequence is AAV2. In some embodiments wherein the vector is an AAV vector, a pseudotyping approach is employed, wherein the genome of one ITR serotype is packaged into a different serotype capsid. See e.g., Zolutuhkin S. et al. Methods 28(2): 158-67 (2002). In preferred embodiments, the serotype of the AAV ITRs of the AAV vector and the serotype of the capsid sequence of the AAV vector are independently selected from the group consisting of AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10, AAV11, and AAV12. In some embodiments of the present invention wherein the vector is a rAAV vector, a mutant capsid sequence is employed. Mutant capsid sequences, as well as other techniques such as rational mutagenesis, engineering of targeting peptides, generation of chimeric particles, library and directed evolution approaches, and immune evasion modifications, may be employed in the present invention to optimize AAV vectors, for purposes such as achieving immune evasion and enhanced therapeutic output. See e.g., Mitchell A.M. et al. AAV’s anatomy: Roadmap for optimizing vectors for translational success. Curr Gene Ther.10(5): 319-340. AAV vectors can mediate long term gene expression in the retina and elicit minimal immune responses making these vectors an attractive choice for gene delivery to the eye. IV. METHODS OF PRODUCING VIRAL VECTORS The present disclosure also provides methods of making a recombinant adeno-associated viral (rAAV) vectors comprising inserting into an adeno-associated viral vector any one of the nucleic acids described herein. According to some embodiments, the rAAV vector further comprises one or more AAV inverted terminal repeats (ITRs). According to the methods of making an rAAV vector that are provided by the disclosure, the serotype of the capsid sequence and the serotype of the ITRs of said AAV vector are independently selected from the group consisting of AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10, AAV11, and AAV12. Thus, the disclosure encompasses vectors that use a pseudotyping approach, wherein the vector genome of one ITR serotype is packaged into a different serotype capsid. See e.g., Daya S. and Berns, K.I., Gene therapy using adeno-associated virus vectors. Clinical Microbiology Reviews, 21(4): 583-593 (2008) (hereinafter Daya et al.). Furthermore, in some embodiments, the capsid sequence is a mutant capsid sequence. AAV Vectors AAV vectors are derived from adeno-associated virus, which has its name because it was originally described as a contaminant of adenovirus preparations. AAV vectors offer numerous well-known advantages over other types of vectors: wildtype strains infect humans and nonhuman primates without evidence of disease or adverse effects; the AAV capsid displays very low immunogenicity combined with high chemical and physical stability which permits rigorous methods of virus purification and concentration; AAV vector transduction leads to sustained transgene expression in post-mitotic, nondividing cells and provides long-term gain of function; and the variety of AAV subtypes and variants offers the possibility to target selected tissues and cell types. Heilbronn R & Weger S, Viral Vectors for Gene Transfer: Current Status of Gene Therapeutics, in M. Schäfer-Korting (ed.), Drug Delivery, Handbook of Experimental Pharmacology, 197: 143-170 (2010) (hereinafter Heilbronn). A major limitation of AAV vectors is that the AAV offers only a limited transgene capacity (<4.9 kb) for a conventional vector containing single-stranded DNA. AAV is a nonenveloped, small, single-stranded DNA-containing virus encapsidated by an icosahedral, 20 nm diameter capsid. The human serotype AAV2 was used in a majority of early studies of AAV. Heilbronn (2010). It contains a 4.7 kb linear, single-stranded DNA genome with two open reading frames rep and cap (“rep” for replication and “cap” for capsid). Rep codes for four overlapping nonstructural proteins: Rep78, Rep68, Rep52, and Rep40. Rep78 and Rep69 are required for most steps of the AAV life cycle, including the initiation of AAV DNA replication at the hairpin-structured inverted terminal repeats (ITRs), which is an essential step for AAV vector production. The cap gene codes for three capsid proteins, VP1, VP2, and VP3. Rep and cap are flanked by the 145 bp ITRs. The ITRs contain the origins of DNA replication and the packaging signals, and they serve to mediate chromosomal integration. The ITRs are generally the only AAV elements maintained in AAV vector construction. To achieve replication, AAVs must be coinfected into the target cell with a helper virus. Grieger JC & Samulski RJ, Adeno-associated virus as a gene therapy vector: Vector development, production, and clinical applications. Adv Biochem Engin/Biotechnol 99:119-145 (2005). Typically, helper viruses are either adenovirus (Ad) or herpes simplex virus (HSV). In the absence of a helper virus, AAV can establish a latent infection by integrating into a site on human chromosome 19. Ad or HSV infection of cells latently infected with AAV will rescue the integrated genome and begin a productive infection. The four Ad proteins required for helper function are E1A, E1B, E4, and E2A. In addition, synthesis of Ad virus-associated (VA) RNAs is required. Herpesviruses can also serve as helper viruses for productive AAV replication. Genes encoding the helicase-primase complex (UL5, UL8, and UL52) and the DNA-binding protein (UL29) have been found sufficient to mediate the HSV helper effect. In some embodiments of the present invention that employ rAAV vectors, the helper virus is an adenovirus. In other embodiments that employ rAAV vectors, the helper virus is HSV. Making recombinant AAV (rAAV) vectors The production, purification, and characterization of the rAAV vectors of the present invention may be carried out using any of the many methods known in the art. For reviews of laboratory-scale production methods, see, e.g., Clark RK, Kidney Int.61s:9-15 (2002); Choi VW et al., Current Protocols in Molecular Biology 16.25.1-16.25.24 (2007) (hereinafter Choi et al.); Grieger JC & Samulski RJ, Adv Biochem Engin/Biotechnol 99:119-145 (2005) (hereinafter Grieger & Samulski); Heilbronn R & Weger S, in M. Schäfer-Korting (ed.), Drug Delivery, Handbook of Experimental Pharmacology, 197: 143-170 (2010) (hereinafter Heilbronn); Howarth JL et al., Cell Biol Toxicol 26:1-10 (2010) (hereinafter Howarth). The production methods described below are intended as non-limiting examples. AAV vector production may be accomplished by cotransfection of packaging plasmids. Heilbronn. The cell line supplies the deleted AAV genes rep and cap and the required helpervirus functions. The adenovirus helper genes, VA-RNA, E2A and E4 are transfected together with the AAV rep and cap genes, either on two separate plasmids or on a single helper construct. A recombinant AAV vector plasmid wherein the AAV capsid genes are replaced with a transgene expression cassette (comprising the gene of interest, e.g., an achromatopsia (ACHM)-associated gene, such as a CNGB3 nucleic acid and/or a CNGA3 nucleic acid as described herein; a promoter; and minimal regulatory elements) bracketed by ITRs, is also transfected. These packaging plasmids can be transfected into adherent or suspension cell lines. According to some embodiments, these packaging plasmids are typically transfected into HEK 293 or HEK293T cells, a human cell line that constitutively expresses the remaining required Ad helper genes, E1A and E1B. This leads to amplification and packaging of the AAV vector carrying the gene of interest. Multiple serotypes of AAV, including 12 human serotypes and more than 100 serotypes from nonhuman primates have now been identified. Howarth et al. The AAV vectors of the present invention may comprise capsid sequences derived from AAVs of any known serotype. As used herein, a “known serotype” encompasses capsid mutants that can be produced using methods known in the art. Such methods include, for example, genetic manipulation of the viral capsid sequence, domain swapping of exposed surfaces of the capsid regions of different serotypes, and generation of AAV chimeras using techniques such as marker rescue. See Bowles et al. Journal of Virology, 77(1): 423-432 (2003), as well as references cited therein. Moreover, the AAV vectors of the present invention may comprise ITRs derived from AAVs of any known serotype. Preferentially, the ITRs are derived from one of the human serotypes AAV1-AAV12. In some embodiments of the present invention, a pseudotyping approach is employed, wherein the genome of one ITR serotype is packaged into a different serotype capsid. Preferentially, the capsid sequences employed in the present invention are derived from one of the human serotypes AAV1-AAV12. Recombinant AAV vectors containing an AAV5 serotype capsid sequence have been demonstrated to target retinal cells in vivo. See, for example, Komaromy et al. Therefore, in preferred embodiments of the present invention, the serotype of the capsid sequence of the AAV vector is AAV2. In other embodiments, the serotype of the capsid sequence of the AAV vector is AAV1, AAV2, AAV3, AAV4, AAV6, AAV7, AAV8, AAV9, AAV10, AAV11, or AAV12. Even when the serotype of the capsid sequence does not naturally target retinal cells, other methods of specific tissue targeting may be employed. See Howarth et al. One possible protocol for the production, purification, and characterization of recombinant AAV (rAAV) vectors is provided in Choi et al. Generally, the following steps are involved: design a transgene expression cassette, design a capsid sequence for targeting a specific receptor, generate adenovirus-free rAAV vectors, purify and titer. These steps are summarized below and described in detail in Choi et al. The transgene expression cassette may be a single-stranded AAV (ssAAV) vector or a “dimeric” or self-complementary AAV (scAAV) vector that is packaged as a pseudo-double- stranded transgene. Choi et al.; Heilbronn; Howarth. Using a traditional ssAAV vector generally results in a slow onset of gene expression (from days to weeks until a plateau of transgene expression is reached) due to the required conversion of single-stranded AAV DNA into double-stranded DNA. In contrast, scAAV vectors show an onset of gene expression within hours that plateaus within days after transduction of quiescent cells. Heilbronn. However, the packaging capacity of scAAV vectors is approximately half that of traditional ssAAV vectors. Choi et al. Alternatively, the transgene expression cassette may be split between two AAV vectors, which allows delivery of a longer construct. See e.g., Dyka et al. Hum Gene Ther.2019 Sep 30. A ssAAV vector can be constructed by digesting an appropriate plasmid (such as, for example, a plasmid containing the achromatopsia (ACHM)-associated gene, such as the CNGB3 nucleic gene and/or the CNGA3 gene) with restriction endonucleases to remove the rep and cap fragments, and gel purifying the plasmid backbone containing the AAVwt-ITRs. Choi et al. Subsequently, the desired transgene expression cassette can be inserted between the appropriate restriction sites to construct the single-stranded rAAV vector plasmid. A scAAV vector can be constructed as described in Choi et al. Then, a large-scale plasmid preparation (at least 1 mg) of the rAAV vector and the suitable AAV helper plasmid and pXX6 Ad helper plasmid can be purified (Choi et al.). A suitable AAV helper plasmid may be selected from the pXR series, pXR1-pXR5, which respectively permit cross-packaging of AAV2 ITR genomes into capsids of AAV serotypes 1 to 12 and variants thereof. The appropriate capsid may be chosen based on the efficiency of the capsid’s targeting of the cells of interest. For example, in a preferred embodiment of the present invention, the serotype of the capsid sequence of the rAAV vector is AAV2, because this type of capsid is known to effectively target retinal cells. Known methods of varying genome (i.e., transgene expression cassette) length and AAV capsids may be employed to improve expression and/or gene transfer to specific cell types (e.g., retinal cone cells). See, e.g., Yang GS, Journal of Virology, 76(15): 7651-7660. Next, HEK293 or HEK293T cells are transfected with pXX6 helper plasmid, rAAV vector plasmid, and AAV helper plasmid. Choi et al. Subsequently the fractionated cell lysates are subjected to a multistep process of rAAV purification, followed by either CsCl gradient purification, or heparin sepharose column purification. The production and quantitation of rAAV virions may be determined using a dot-blot assay. In vitro transduction of rAAV in cell culture can be used to verify the infectivity of the virus and functionality of the expression cassette. In addition to the methods described in Choi et al., various other transfection & purification methods for production of AAV may be used in the context of the present invention. For example, transient transfection methods are available, including methods that rely on a calcium phosphate precipitation or PEI protocol. The various purification methods include iodixanol gradient purification, affinity and/or ion-exchanger column chromatography. In addition to the laboratory-scale methods for producing rAAV vectors, the present invention may utilize techniques known in the art for bioreactor-scale manufacturing of AAV vectors, including, for example, Heilbronn; Clement, N. et al. Human Gene Therapy, 20: 796- 606. According to some embodiments, the method for producing rAAV vectors is carried out as described in Chulay et al. (Hum Gene Ther.2011 Feb;22(2):155-65), incorporated by reference in its entirety herewith. V. METHODS OF SELECTION AND TREATMENT The present disclosure provides methods that can be used in the treatment of retinal diseases or disorders, including, without limitation, achromatopsia (ACHM). In particular, the present invention provides methods of treatment or methods of selecting a subject for treatment of a retinal disease or disorder, including, without limitation, achromatopsia (ACHM), for example, based on an analysis of the subject’s retinal structure and/or function. Additionally, the present invention provides methods for predicting or determining a subject’s likely response to a therapy for treating achromatopsia (ACHM), and methods for determining a subject’s suitability to a treatment regime or intervention for achromatopsia (ACHM), for example, based on an analysis of the subject’s retinal structure and/or function. In certain embodiments, an analysis of the subject’s retinal structure and/or function may comprise an analysis by central fundus autofluorescence and/or optical coherence tomography morphology. Central Fundus Autofluorescence as a Predictor for Achromatopsia Therapy Fundus autofluorescence (FAF) is a non-invasive retinal imaging modality used, for example, to provide a density map of lipofuscin, the predominant ocular fluorophore, in the retinal pigment epithelium. Multiple commercially available imaging systems may be used to obtain FAF images, including the fundus camera, the confocal scanning laser ophthalmoscope, and the ultra-widefield imaging device. With respect to the instant invention, it is understood that, in certain embodiments, identifying a subject or selecting a subject based on an analysis of the subject’s retinal structure and/or function, can include any of a number of acts including, but not limited to, performing a test and observing a result that is indicative of a subject having a specific pattern of fundus autofluorescence; reviewing a test result of a subject and identifying the subject as having a specific pattern of fundus autofluorescence; reviewing documentation on a subject stating that the subject has a specific pattern of fundus autofluorescence and identifying the subject as the one discussed in the documentation by confirming the identity of the subject e.g., by an identification card, hospital bracelet, asking the subject for his/her name and/ or other personal information to confirm the subjects identity. In certain embodiments, identifying a subject or selecting a subject may comprise selecting the subject if a predetermined pattern of fundus autofluorescence (FAF) is present in an eye of the subject at baseline. In certain embodiments, identifying a subject or selecting a subject may comprise classifying the pattern of fundus autofluorescence (FAF) in the eye of the subject as comprising central hypoautofluorescence (grade 0), normal autofluorescence (grade 1), or mild or strong hyperautofluorescence (grade 2). In certain embodiments, (a) a pattern of FAF comprising central hypoautofluorescence (grade 0) identifies a subject that is less likely to be a visual field responder; (b) a pattern of FAF comprising normal autofluorescence (grade 1) identifies a subject that is less likely to be a visual field responder; and/or (c) a pattern of FAF comprising mild or strong hyperautofluorescence (grade 2) identifies a subject that is more likely to be a visual field responder. In certain embodiments, the predetermined pattern of fundus autofluorescence (FAF) may be mild or strong hyperautofluorescence (grade 2). In certain embodiments, the predetermined pattern of fundus autofluorescence (FAF) in the eye of the subject is obtained prior to or at the time of administration of the therapy suitable for treating achromatopsia (ACHM). In certain embodiments, identifying a subject or selecting a subject may comprise monitoring the pattern of fundus autofluorescence (FAF) in the eye of the subject for a period of time after administration of the therapy suitable for treating achromatopsia (ACHM). Optical Coherence Tomography Morphology as a Predictor for Achromatopsia Therapy With respect to the instant invention, it is understood that, in certain embodiments, identifying a subject or selecting a subject based on an analysis of the subject’s retinal structure and/or function, can include any of a number of acts including, but not limited to, performing a test and observing a result that is indicative of a subject having a specific optical coherence tomography (OCT) central outer retina morphology; reviewing a test result of a subject and identifying the subject as having a specific optical coherence tomography (OCT) central outer retina morphology; reviewing documentation on a subject stating that the subject has a specific optical coherence tomography (OCT) central outer retina morphology and identifying the subject as the one discussed in the documentation by confirming the identity of the subject e.g., by an identification card, hospital bracelet, asking the subject for his/her name and/ or other personal information to confirm the subjects identity. In certain embodiments, identifying a subject or selecting a subject may comprise selecting the subject if a predetermined optical coherence tomography (OCT) central outer retina morphology is present in an eye of the subject at baseline. In certain embodiments, identifying a subject or selecting a subject may comprise classifying the optical coherence tomography (OCT) central outer retina morphology in the eye of the subject as comprising central absence of ellipsoid zone (EZ) line disturbance (grade 0), the presence of EZ line disturbance (grade 1), or the presence of empty optical space (grade 2). In certain embodiments, (a) an OCT central outer retina morphology comprising the central absence of ellipsoid zone (EZ) line disturbance (grade 0) identifies a subject that is more likely to be a visual field responder; (b) an OCT central outer retina morphology comprising the presence of EZ line disturbance (grade 1) identifies a subject that is more likely to be a visual field responder; and/or (c) an OCT central outer retina morphology comprising the presence of empty optical space (grade 2) identifies a subject that is less likely to be a visual field responder. In certain embodiments, the predetermined optical coherence tomography (OCT) central outer retina morphology is central absence of ellipsoid zone (EZ) line disturbance (grade 0) or presence of EZ line disturbance (grade 1). Accordingly, in one aspect, the instant invention provides a method of treating a subject, comprising: (a) selecting the subject if a predetermined pattern of fundus autofluorescence (FAF) is present in an eye of the subject at baseline; and (b) administering to the subject an effective amount of a therapy suitable for treating achromatopsia (ACHM). In another aspect, the instant invention provides a method of selecting and treating a subject predisposed to achromatopsia (ACHM), comprising: (a) selecting the subject if a predetermined pattern of fundus autofluorescence (FAF) is present in an eye of the subject at baseline; and (b) administering to the subject an effective amount of a therapy suitable for treating achromatopsia (ACHM). In another aspect, the instant invention provides a method of selecting and treating a subject having achromatopsia (ACHM) that is likely to be a visual field responder, comprising: (a) selecting the subject if a predetermined pattern of fundus autofluorescence (FAF) is present in an eye of the subject at baseline; and (b) administering to the subject an effective amount of a therapy suitable for treating achromatopsia (ACHM). In another aspect, the instant invention provides a method of reducing, inhibiting and/or preventing one or more symptoms of achromatopsia (ACHM) in a subject, comprising: (a) selecting the subject if a predetermined pattern of fundus autofluorescence (FAF) is present in an eye of the subject at baseline; and (b) administering to the subject an effective amount of a therapy suitable for treating achromatopsia (ACHM). In certain embodiments, the methods described herein may further comprise classifying the pattern of fundus autofluorescence (FAF) in the eye of the subject as comprising central hypoautofluorescence (grade 0), normal autofluorescence (grade 1), or mild or strong hyperautofluorescence (grade 2). In certain embodiments, a pattern of FAF comprising central hypoautofluorescence (grade 0) identifies a subject that is less likely to be a visual field responder. In certain embodiments, a pattern of FAF comprising normal autofluorescence (grade 1) identifies a subject that is less likely to be a visual field responder. In certain embodiments, a pattern of FAF comprising mild or strong hyperautofluorescence (grade 2) identifies a subject that is more likely to be a visual field responder In certain embodiments a subject is selected based on the predetermined pattern of fundus autofluorescence (FAF) is mild or strong hyperautofluorescence (grade 2). In certain embodiments, the predetermined pattern of fundus autofluorescence (FAF) in the eye of the subject is obtained prior to or at the time of administration of the therapy suitable for treating achromatopsia (ACHM). In certain embodiments, the methods described herein may further comprise monitoring the pattern of fundus autofluorescence (FAF) in the eye of the subject for a period of time after administration of the therapy suitable for treating achromatopsia (ACHM). In one aspect, the instant invention provides a method of treating a subject, comprising: (a) selecting the subject if a predetermined optical coherence tomography (OCT) central outer retina morphology is present in an eye of the subject at baseline; and (b) administering to the subject an effective amount of a therapy suitable for treating achromatopsia (ACHM). In one aspect, the instant invention provides a method of selecting and treating a subject predisposed to achromatopsia (ACHM), comprising: (a) selecting the subject if a predetermined optical coherence tomography (OCT) central outer retina morphology is present in an eye of the subject at baseline; and (b) administering to the subject an effective amount of a therapy suitable for treating achromatopsia (ACHM). In one aspect, the instant invention provides a method of selecting and treating a subject having achromatopsia (ACHM) that is more likely to be a visual field responder, comprising: (a) selecting the subject if a predetermined optical coherence tomography (OCT) central outer retina morphology is present in an eye of the subject at baseline; and (b) administering to the subject an effective amount of a therapy suitable for treating achromatopsia (ACHM). In one aspect, the instant invention provides a method of reducing, inhibiting and/or preventing one or more symptoms of achromatopsia (ACHM) in a subject, comprising: (a) selecting the subject if a predetermined optical coherence tomography (OCT) central outer retina morphology is present in an eye of the subject at baseline; and (b) administering to the subject an effective amount of a therapy suitable for treating achromatopsia (ACHM). In certain embodiments, the methods described herein may further comprise classifying the optical coherence tomography (OCT) central outer retina morphology in the eye of the subject as comprising central absence of ellipsoid zone (EZ) line disturbance (grade 0), the presence of EZ line disturbance (grade 1), or the presence of empty optical space (grade 2). In certain embodiments, an OCT central outer retina morphology comprising the central absence of ellipsoid zone (EZ) line disturbance (grade 0) identifies a subject that is more likely to be a visual field responder. In certain embodiments, an OCT central outer retina morphology comprising the presence of EZ line disturbance (grade 1) identifies a subject that is more likely to be a visual field responder. In certain embodiments, an OCT central outer retina morphology comprising the presence of empty optical space (grade 2) identifies a subject that is less likely to be a visual field responder. In certain embodiments, the predetermined optical coherence tomography (OCT) central outer retina morphology is central absence of ellipsoid zone (EZ) line disturbance (grade 0) or presence of EZ line disturbance (grade 1). In certain embodiments, the predetermined optical coherence tomography (OCT) central outer retina morphology in the eye of the subject is obtained prior to or at the time of administration of the therapy suitable for treating achromatopsia (ACHM). In certain embodiments, the methods described herein may further comprise monitoring the optical coherence tomography (OCT) central outer retina morphology in the eye of the subject for a period of time after administration of the therapy suitable for treating achromatopsia (ACHM). In certain embodiments, the methods described herein may further comprise testing the subject for a visual field response. In certain embodiments, the subject is a visual field responder. Achromatopsia is a color vision disorder. Autosomal recessive mutations or other types of sequence alterations in three genes are the predominant cause of congenital achromatopsia. See Pang, J.-J. et al. (2010). Achromatopsia as a Potential Candidate for Gene Therapy. In Advances in Experimental Medicine and Biology, Volume 664, Part 6, 639-646 (2010). Achromatopsia has been associated with mutations in either the alpha or beta subunits of cyclic nucleotide gated channels (CNGs), which are respectively known as CNGA3 and CNGB3. Mutations in the CNGA3 gene that were associated with achromatopsia are reported in Patel KA, et al. Transmembrane S1 mutations in CNGA3 from achromatopsia 2 patients cause loss of function and impaired cellular trafficking of the cone CNG channel. Invest. Ophthalmol. Vis. Sci.46 (7): 2282–90. (2005)., Johnson S, et al. Achromatopsia caused by novel mutations in both CNGA3 and CNGB3. J. Med. Genet.41 (2): e20. (2004)., Wissinger B, et al. CNGA3 mutations in hereditary cone photoreceptor disorders. Am. J. Hum. Genet.69 (4): 722– 37.(2001)., and Kohl S, et al. Total colourblindness is caused by mutations in the gene encoding the alpha-subunit of the cone photoreceptor cGMP-gated cation channel. Nat. Genet.19 (3): 257–9. (1998). Mutations in CNGB3 gene that were associated with achromatopsia are reported in Johnson S, et al. Achromatopsia caused by novel mutations in both CNGA3 and CNGB3. J. Med. Genet.41 (2): e20. (2004)., Peng C, et al. Achromatopsia-associated mutation in the human cone photoreceptor cyclic nucleotide-gated channel CNGB3 subunit alters the ligand sensitivity and pore properties of heteromeric channels. J. Biol. Chem.278 (36): 34533–40 (2003)., Bright SR, et al. Disease-associated mutations in CNGB3 produce gain of function alterations in cone cyclic nucleotide-gated channels. Mol. Vis.11: 1141–50 (2005)., Kohl S, et al. CNGB3 mutations account for 50% of all cases with autosomal recessive achromatopsia. Eur. J. Hum. Genet.13 (3): 302–8 (2005)., Rojas CV, et al. A frameshift insertion in the cone cyclic nucleotide gated cation channel causes complete achromatopsia in a consanguineous family from a rural isolate. Eur. J. Hum. Genet.10 (10): 638–42 (2002)., Kohl S, et al. Mutations in the CNGB3 gene encoding the beta-subunit of the cone photoreceptor cGMP-gated channel are responsible for achromatopsia (ACHM3) linked to chromosome 8q21. Hum. Mol. Genet.9 (14): 2107–16 (2000)., Sundin OH, et al.. Genetic basis of total colourblindness among the Pingelapese islanders. Nat. Genet.25 (3): 289–93 (2000). Sequence alterations in the gene for cone cell transducin, known as GNAT2, can also cause achromatopsia. See Kohl S, et al., Mutations in the cone photoreceptor G-protein alpha-subunit gene GNAT2 in patients with achromatopsia. Kokl S, et al. Mutations in the cone photoreceptor G-protein alpha-subunit gene GNAT2 in patients with achromatopsia. Am J Hum Genet 71 (2): 422-425 (2002) (hereinafter Kohl et al.). The severity of mutations in these proteins correlates with the severity of the achromatopsia phenotype. Mutations in CNGB3 account for about 50% of cases of achromatopsia. Kohl et al. Mutations in CNGA3 account for about 23% of cases, and mutations in GNAT2 account for about 2% of cases. The “CNGB3 gene” is the gene that encodes the cyclic nucleotide-gated channel beta 3 (CNGB3). The “CNGA3 gene” is the gene that encodes the cyclic nucleotide-gated channel alpha 3 (CNGA3). The CNGB3 and CNGA3 genes are expressed in cone cells of the retina. Native retinal cyclic nucleotide gated channels (CNGs) are critically involved in phototransduction. CNGs are cation channels that consist of two alpha and two beta subunits. In the dark, cones have a relatively high concentration of cyclic guanosine 3'-5' monophosphate (cGMP), which causes the CNGs to open, resulting in depolarization and continuous glutamate release. Light exposure activates a signal transduction pathway that breaks down cGMP. The reduction in cGMP concentration causes the CNGs to close, preventing the influx of positive ions, hyperpolarizing the cell, and stopping the release of glutamate. Mutations in either the CNGB3 or CNGA3 genes can cause defects in cone photoreceptor function resulting in achromatopsia. Mutations in the CNGB3 gene have been associated with other diseases in addition to achromatopsia, including progressive cone dystrophy and juvenile macular degeneration. The GNAT2 gene encodes the alpha-2 subunit of guanine nucleotide binding protein, which is also known as the cone-specific alpha transducin. Guanine nucleotide-binding proteins (G proteins) consist of alpha, beta, and gamma subunits. In photoreceptors, G proteins are critical in the amplification and transduction of visual signals. Various types of sequence alterations in GNAT2 can cause human achromatopsia: nonsense mutations, small deletion and/or insertion mutations, frameshift mutations, and large intragenic deletions. Pang et al. Currently, there is no effective treatment for achromatopsia. Animal studies suggest that it is possible to use gene therapy to treat achromatopsia and other diseases of the retina. For recessive gene defects, the goal is to deliver a wild-type copy of a defective gene to the affected retinal cell type. The ability to deliver genes to some subsets of cone cells was demonstrated, for example, in Mauck, M. C. et al., Longitudinal evaluation of expression of virally delivered transgenes in gerbil cone photoreceptors. Visual Neuroscience 25(3): 273-282 (2008). The authors showed that a recombinant AAV vector could be used to achieve long-term expression of a reporter gene encoding green fluorescent protein in specific types of gerbil cone cells. The authors further demonstrated that a human long-wavelength opsin gene could be delivered to specific gerbil cones, resulting in cone responses to long-wavelength light. Other studies demonstrated that gene therapy with recombinant AAV vectors could be used to convert dichromat monkeys into trichromats by introducing a human L-opsin gene into the squirrel monkey retina. Mancuso, K., et al. Gene therapy for red-green colour blindness in adult primates. Nature 461: 784-787 (2009). Electroretinograms verified that the introduced photopigment was functional, and the monkeys showed improved color vision in a behavioral test. There are several animal models of achromatopsia for which gene therapy experiments have demonstrated the ability to restore cone function. See Pang et al. First, the Gnat2^cpfl3 mouse has a recessive mutation in the cone-specific alpha transducin gene, resulting in poor visual acuity and little or no cone-specific ERT response. Treatment of homozygous Gnat2^cpfl3 mice with a single subretinal injection of an AAV serotype 5 vector carrying wild type mouse GNAT2 cDNA and a human red cone opsin promoter restored cone-specific ERG responses and visual acuity. Alexander et al. Restoration of cone vision in a mouse model of achromatopsia. Nat Med 13:685-687 (2007) (hereinafter Alexander et al.). Second, the cpfl5 (Cone Photoreceptor Function Loss 5) mouse has an autosomal recessive missense mutation in the CNGA3 gene with no cone-specific ERG response. Treatment of cpfl5 mice with subretinal injection of an AAV vector carrying the wild type mouse CNGA3 gene and a human blue cone promoter (HB570) resulted in restoration of cone-specific ERG responses. Pang et al. Third, there is an Alaskan Malamute dog that has a naturally occurring CNGB3 mutation causing loss of daytime vision and absence of retinal cone function. In this type of dog, subretinal injection of an AAV5 vector containing human CNGB3 cDNA and a human red cone opsin promoter restored cone-specific ERG responses. See, e.g., Komaromy et al. According to some embodiments, the disclosure further provides methods for treating a retinal or ocular disease or disorder (e.g. ACHM) comprising administering any of the vectors of the invention to a subject in need of such treatment, thereby treating the subject. In any of the methods of treatment, the vector can be any type of vector known in the art. In some embodiments, the vector is a non-viral vector, such as a naked DNA plasmid, an oligonucleotide (such as, e.g., an antisense oligonucleotide, a small molecule RNA (siRNA), a double stranded oligodeoxynucleotide, or a single stranded DNA oligonucleotide). In specific embodiments involving oligonucleotide vectors, delivery may be accomplished by in vivo electroporation (see e.g., Chalberg et al., 2005) or electron avalanche transfection (see e.g., Chalberg et al.2006). In further embodiments, the vector is a dendrimer/DNA complex that may optionally be encapsulated in a water soluble polymer, a DNA-compacting peptide (see e.g., Farjo et al.2006, where CK30, a peptide containing a cysteine residue coupled to poly ethylene glycol followed by 30 lysines, was used for gene transfer to photoreceptors), a peptide with cell penetrating properties (see Johnson et al.2007; Barnett et al., 2006; Cashman et al., 2003; Schorder et al., 2005; Kretz et al.2003 for examples of peptide delivery to ocular cells), or a DNA-encapsulating lipoplex, polyplex, liposome, or immunoliposome (see e.g., Zhang et al.2003; Zhu et al.2002; Zhu et al.2004). According to some embodiments, the vector is a viral vector, such as a vector derived from an adeno-associated virus, an adenovirus, a retrovirus, a lentivirus, a vaccinia/poxvirus, or a herpesvirus (e.g., herpes simplex virus (HSV)). See e.g., Howarth. In preferred embodiments, the vector is an adeno-associated viral (AAV) vector. According to some embodiments, the disclosure provides methods for treating a retinal or ocular disease or disorder (e.g. ACHM) comprising administering a rAAV vector described herein, wherein the rAAV vector comprises a nucleic acid sequence encoding CNGB3 and/or CNGA3. According to some embodiments, the nucleic acid sequences described herein are directly introduced into a cell, where the nucleic acid sequences are expressed to produce the encoded product, prior to administration in vivo of the resulting recombinant cell. This can be accomplished by any of numerous methods known in the art, e.g., by such methods as electroporation, lipofection, calcium phosphate mediated transfection. Pharmaceutical Compositions According to some aspects, the disclosure provides pharmaceutical compositions comprising any of the vectors described herein, optionally in a pharmaceutically acceptable excipient. As is well known in the art, pharmaceutically acceptable excipients are relatively inert substances that facilitate administration of a pharmacologically effective substance and can be supplied as liquid solutions or suspensions, as emulsions, or as solid forms suitable for dissolution or suspension in liquid prior to use. For example, an excipient can give form or consistency, or act as a diluent. Suitable excipients include but are not limited to stabilizing agents, wetting and emulsifying agents, salts for varying osmolarity, encapsulating agents, pH buffering substances, and buffers. Such excipients include any pharmaceutical agent suitable for direct delivery to the eye which may be administered without undue toxicity. Pharmaceutically acceptable excipients include, but are not limited to, sorbitol, any of the various TWEEN compounds, and liquids such as water, saline, glycerol and ethanol. Pharmaceutically acceptable salts can be included therein, for example, mineral acid salts such as hydrochlorides, hydrobromides, phosphates, sulfates, and the like; and the salts of organic acids such as acetates, propionates, malonates, benzoates, and the like. A thorough discussion of pharmaceutically acceptable excipients is available in REMINGTON'S PHARMACEUTICAL SCIENCES (Mack Pub. Co., N.J.1991). Generally, these compositions are formulated for administration by ocular injection. Accordingly, these compositions can be combined with pharmaceutically acceptable vehicles such as saline, Ringer's balanced salt solution (pH 7.4), and the like. Although not required, the compositions may optionally be supplied in unit dosage form suitable for administration of a precise amount. Methods of Administration According to the methods of treatment of the present invention, administering of a composition comprising a therapy suitable for treating achromatopsia (ACHM) as described herein or known in the art can be accomplished by any means known in the art. According to the methods of treatment of the present invention, administering of a composition comprising a vector described herein can be accomplished by any means known in the art. According to some embodiments, the therapeutic compositions (e.g., nucleic acids encoding achromatopsia (ACHM)-associated proteins as described herein) are administered alone (i.e., without a vector for delivery). According to some embodiments, the administration is by ocular injection. According to some embodiments, the administration is by subretinal injection. Methods of subretinal delivery are known in the art. For example, see WO 2009/105690, incorporated herein by reference in its entirety. According to some embodiments, the compositions are directly injected into the subretinal space outside the central retina. In other embodiments, the administration is by intraocular injection, intravitreal injection, suprachoroidal, or intravenous injection. Administration of a vector to the retina may be unilateral or bilateral, and may be accomplished with or without the use of general anesthesia. By safely and effectively transducing ocular cells (e.g., RPE) with a composition comprising a vector described herein, wherein the vector comprises a nucleic acid encoding an achromatopsia (ACHM)-associated protein, such as CNGB3 or CNGA3, the methods of the invention may be used to treat an individual; e.g., a human, having retinal or ocular disease or disorder (e.g. ACHM), wherein the transduced cells produce an achromatopsia (ACHM)- associated protein, such as CNGB3 or CNGA3 in an amount sufficient to treat the retinal or ocular disease or disorder (e.g. ACHM). According to some embodiments, compositions may be administered by one or more subretinal injections, either during the same procedure or spaced apart by days, weeks, months, or years. According to some embodiments, multiple injections of a composition comprising a vector described herein, are no more than one hour, two hours, three hours, four hours, five hours, six hours, nine hours, twelve hours or 24 hours apart. According to some embodiments, multiple injections of a composition comprising a vector described herein, are about one month, two months, three months, four months, five months, six months, seven months, eight months, nine months, ten months, eleven months, twelve months or more apart. According to some embodiments, multiple injections of a composition comprising a vector described herein, are one year, two years, three years, four years, five years or more apart. According to some embodiments, multiple vectors may be used to treat the subject. According to the methods of treatment of the present invention, the volume of vector delivered may be determined based on the characteristics of the subject receiving the treatment, such as the age of the subject and the volume of the area to which the vector is to be delivered. It is known that eye size and the volume of the subretinal or ocular space differ among individuals and may change with the age of the subject. According to some embodiments, the volume of the composition injected to the subretinal space of the retina is more than about any one of 1 µl, 2 µl, 3 µl, 4 µl, 5 µl, 6 µl, 7 µl, 8 µl, 9 µl, 10 µl, 15 µl, 20 µl, 25 µl, 50 µl, 75 µl, 100 µl, 200 µl, 300 µl, 400 µl, 500 µl, 600 µl, 700 µl, 800 µl, 900 µl, or 1 mL, or any amount therebetween. According to embodiments wherein the vector is administered subretinally, vector volumes may be chosen with the aim of covering all or a certain percentage of the subretinal or ocular space, or so that a particular number of vector genomes is delivered. According to the methods of treatment of the present disclosure, the concentration of vector that is administered may differ depending on production method and may be chosen or optimized based on concentrations determined to be therapeutically effective for the particular route of administration. According to some embodiments, the concentration in vector genomes per milliliter (vg/ml) is selected from the group consisting of about 10⁸ vg/ml, about 10⁹ vg/ml, about 10¹⁰ vg/ml, about 10¹¹ vg/ml, about 10¹² vg/ml, about 10¹³ vg/ml, and about 10¹⁴ vg/ml or any amount therebetween. In preferred embodiments, the concentration is in the range of 10¹⁰ vg/ml - 10¹³ vg/ml, delivered by subretinal injection or intravitreal injection in a volume of about 0.05 mL, about 0.1 mL, about 0.2 mL, about 0.4 mL, about 0.6 mL, about 0.8 mL, and about 1.0 mL. According to some embodiments, one or more additional therapeutic agents may be administered to the subject. For example, anti-angiogenic agents (e.g., nucleic acids or polypeptides) may be administered to the subject. The effectiveness of the compositions described herein can be monitored by several criteria. For example, after treatment in a subject using methods of the present disclosure, the subject may be assessed for e.g., an improvement and/or stabilization and/or delay in the progression of one or more signs or symptoms of the disease state by one or more clinical parameters including those described herein. Examples of such tests are known in the art, and include objective as well as subjective (e.g., subject reported) measures. For example, to measure the effectiveness of a treatment on a subject's visual function, one or more of the following may be evaluated: the subject's subjective quality of vision, the subject’s dark adaptation, the subject’s improved central vision function (e.g., an improvement in the subject's ability to read fluently and recognize faces), the subject's visual mobility (e.g., a decrease in time needed to navigate a maze), the subject’s visual acuity (e.g., an improvement in the subject's Log MAR score), microperimetry (e.g., an improvement in the subject's dB score), dark-adapted perimetry (e.g., an improvement in the subject's dB score), fine matrix mapping (e.g., an improvement in the subject's dB score), Goldmann perimetry (e.g., a reduced size of scotomatous area (i.e., areas of blindness) and improvement of the ability to resolve smaller targets), flicker sensitivities (e.g., an improvement in Hertz), autofluorescence, and electrophysiology measurements (e.g., improvement in ERG). According to some embodiments, the visual function is measured by the subject's dark adaptation. The Dark Adaptation Test is a test used to determine the ability of the rod photoreceptors to increase their sensitivity in the dark. This test is a measurement of the rate at which the rod and cone system recover sensitivity in the dark following exposure to a bright light source. According to some embodiments, the visual function is measured by the subject's visual mobility. According to some embodiments, the visual function is measured by the subject's visual acuity. According to some embodiments, the visual function is measured by microperimetry. According to some embodiments, the visual function is measured by dark-adapted perimetry. According to some embodiments, the visual function is measured by ERG. According to some embodiments, the visual function is measured by the subject's subjective quality of vision. VI. KITS The rAAV compositions as described herein may be contained within a kit designed for use in one of the methods of the disclosure as described herein. According to some embodiments, a kit of the disclosure comprises (a) any one of the vectors of the disclosure, and (b) instructions for use thereof. According to some embodiments, a vector of the disclosure may be any type of vector known in the art, including a non-viral or viral vector, as described supra. According to some embodiments, the vector is a viral vector, such as a vector derived from an adeno-associated virus, an adenovirus, a retrovirus, a lentivirus, a vaccinia/poxvirus, or a herpesvirus (e.g., herpes simplex virus (HSV)). According to preferred embodiments, the vector is an adeno-associated viral (AAV) vector. According to some embodiments, the kits may further comprise instructions for use. According to some embodiments, the kits further comprise a device for ocular delivery (e.g., intraocular injection, intravitreal injection, suprachoroidal, or intravenous injection) of compositions of rAAV vectors described herein. According to some embodiments, the instructions for use include instructions according to one of the methods described herein. The instructions provided with the kit may describe how the vector can be administered for therapeutic purposes, e.g., for treating a retinal or ocular disease or disorder (e.g., ACHM)). According to some embodiments wherein the kit is to be used for therapeutic purposes, the instructions include details regarding recommended dosages and routes of administration. According to some embodiments, the kits further contain buffers and/or pharmaceutically acceptable excipients. Additional ingredients may also be used, for example preservatives, buffers, tonicity agents, antioxidants and stabilizers, nonionic wetting or clarifying agents, viscosity-increasing agents, and the like. The kits described herein can be packaged in single unit dosages or in multidosage forms. The contents of the kits are generally formulated as sterile and substantially isotonic solution. All patents and publications mentioned herein are incorporated herein by reference to the extend allowed by law for the purpose of describing and disclosing the proteins, enzymes, vectors, host cells, and methodologies reported therein that might be used with the present disclosure. However, nothing herein is to be construed as an admission that the disclosure is not entitled to antedate such disclosure by virtue of prior disclosure. The present disclosure is further illustrated by the following examples, which should not be construed as further limiting. The contents of all figures and all references, patents and published patent applications cited throughout this application, as well as the Figures, are expressly incorporated herein by reference in their entirety. EXAMPLES EXAMPLE 1: Central Fundus Autofluorescence as a Predictor for Achromatopsia Therapy Fundus autofluorescence in Achromatopsia has been evaluated in relatively few studies and its significance is not quite clear. A prospective longitudinal study of retinal structure and function in achromatopsia described three patterns of fundus autofluorescence (FAF) at baseline, a normal FAF pattern a central hyperautofluorescence and a central hypoautofluorescence¹ The hypoautofluorescence pattern seems to be directly correlated to age and disease progression as characterized by SD-OCT changes at the external retina level.^1-4 However there is some controversy regarding the chronology of normal and hyperautofluorescence patterns. Fahim et al suggest that central hyperautofluorescence is associated to early stages of achromatopsia.² Aboshiha et al correlate more disordered SD-OCT structure to more abnormal FAF pattern (graded from normal through hyperautofluorescence to hypoautofluorescence).¹ Interestingly hyperautofluorescence group was the youngest in Aboshiha series although not statistically different. A retrospective analysis was performed in ACHM B3 Study classifying study eyes according to central autofluorescence pattern at baseline. Study eyes were classified into central hypoautofluorescence (grade 0), normal autofluorescence (grade 1), and mild or strong hyperautofluorescence (grade 2) (FIG.1). Autofluorescence grading was compared to Octopus visual field response. Results of this analysis suggest a correlation between mild and strong hyperautofluorescence and the probability of being a visual field responder. None of the six grade 0 or grade 1 eyes became visual field responders. There were six responders among the 15 grade 2 eyes (two mild and four strong hyperautofluorescence). Of note, one subject in ACHM A3 Study is considered an Octopus visual field responder and is classified as grade 2 (mild hyperautofluorescence). FIG.1 depicts representative images from a longitudinal study of retinal structure in ACHM with 50 subjects and a mean follow-up of 62 months showed no change in FAF pattern over time.⁵ Subject 4029 presented stippled central hyperautofluorescence at baseline which gradually decreased after study treatment only in the study eye (FIG.2, FIG.3). EXAMPLE 2: Optical Coherence Tomography Morphology as a Predictor for Achromatopsia Therapy Some Optical Coherence Tomography (OCT) findings in Achromatopsia like foveal hypoplasia are detected in early childhood, most likely resultant of abnormal macular development.⁶ However, other OCT signs like ellipsoid zone (EZ) disturbances, optical empty space (or foveal hyporeflective zone), and outer retina and retinal pigment epithelium atrophy have been associated with age suggesting a progressive natural history of this disease.^1,4,6 Important to emphasize that age is not the only variable determining disease progression and OCT findings evolution. In Yang et al. case series, the youngest subject presented the most severe foveal EZ loss.⁶ Moreover, functional testing, OCT findings and age may not present a specific correlation in achromatopsia. Zobor et al. reported a case series of 36 subjects with CNGA3-related achromatopsia classifying the OCT characteristics into 5 categories: (1) continuous inner segment ellipsoid zone (EZ), (2) EZ disruption, (3) absence of EZ, (4) presence of a hyporeflective zone (HRZ), and (5) outer retinal atrophy including RPE loss.^7,8 Age distribution and functional testing results were similar among those OCT categories, except for older age in the group presenting outer retinal and RPE atrophy. Results in the literature are conflicting even for the relationship between EZ grade and foveal cone density.⁹ Although the progressiveness of natural history in achromatopsia is complex open discussion, it seems reasonable to consider the presence of optical empty space (EOS) and outer retina and retinal pigment epithelium atrophy on OCT as signs of advanced disease stages. A retrospective analysis was performed in ACHM B3 and A3 Studies classifying study eyes according to OCT central outer retina morphology at baseline. Study eyes were classified into central absence of EZ line disturbance (grade 0), presence of EZ line disturbance (grade 1), or presence of empty optical space (grade 2) (FIG.4). OCT outer retina grading was compared to Octopus visual field response. Results of this analysis suggest a different distribution of OCT outer retina categories between studies. In ACHM B3 study more than two thirds of study eyes were classified as grade 0 whereas in ACHM A3 study less than a third presented the same grading (FIG.5). The fact that convincing Octopus visual field responders were mostly seen in ACHM B3 study suggest that eyes with more severe OCT findings are less likely to respond to therapy. None of two B3 subjects with Optical Empty Space are considered visual field responders. The one subject in ACHM A3 Study considered an Octopus visual field responder is classified as grade 0 (No EZ disturbance). Interestingly, some studies suggest that CNGA3-related achromatopsia might be more severe than CNGB3-related achromatopsia.^1,10,11 References 1. Aboshiha J, Dubis AM, Cowing J, Fahy RT, Sundaram V, Bainbridge JW, Ali RR, Dubra A, Nardini M, Webster AR, Moore AT, Rubin G, Carroll J, Michaelides M. A prospective longitudinal study of retinal structure and function in achromatopsia. Invest Ophthalmol Vis Sci. 2014 Aug 7;55(9):5733-43 2. Fahim AT, Khan NW, Zahid S, Schachar IH, Branham K, Kohl S, Wissinger B, Elner VM, Heckenlively JR, Jayasundera T. Diagnostic fundus autofluorescence patterns in achromatopsia. Am J Ophthalmol.2013 Dec;156(6):1211-1219. 3. Matet A, Kohl S, Baumann B, Antonio A, Mohand-Said S, Sahel JA, Audo I. Multimodal imaging including semiquantitative short-wavelength and near-infrared autofluorescence in achromatopsia Sci Rep 2018 Apr 4;8(1):5665 4. Greenberg JP, Sherman J, Zweifel SA, Chen RW, Duncker T, Kohl S, Baumann B, Wissinger B, Yannuzzi LA, Tsang SH. Spectral-domain optical coherence tomography staging and autofluorescence imaging in achromatopsia. JAMA Ophthalmol.2014 Apr 1;132(4):437-45. 5. Hirji N, Georgiou M, Kalitzeos A, Bainbridge JW, Kumaran N, Aboshiha J, Carroll J, Michaelides M. Longitudinal Assessment of Retinal Structure in Achromatopsia Patients With Long-Term Follow-up. Invest Ophthalmol Vis Sci.2018 Dec 3;59(15):5735-5744. 6. Yang P, Michaels KV, Courtney RJ, Wen Y, Greninger DA, Reznick L, Karr DJ, Wilson LB, Weleber RG, Pennesi ME. Retinal morphology of patients with achromatopsia during early childhood: implications for gene therapy. JAMA Ophthalmol.2014 Jul;132(7):823- 31. 7. Sundaram V, Wilde C, Aboshiha J, et al. Retinal structure and function in achromatopsia: implications for gene therapy. Ophthalmology.2014;121:234–245. 8. Zobor D, Werner A, Stanzial F, Benedicenti F, Rudolph G, Kellner U, Hamel C, Andréasson S, Zobor G, Strasser T, Wissinger B, Kohl S, Zrenner E; RD-CURE Consortium. The Clinical Phenotype of CNGA3-Related Achromatopsia: Pretreatment Characterization in Preparation of a Gene Replacement Therapy Trial. Invest Ophthalmol Vis Sci.2017 Feb 1;58(2):821-832. 9. Litts KM, Woertz EN, Wynne N, Brooks BP, Chacon A, Connor TB Jr, Costakos D, Dumitrescu A, Drack AV, Fishman GA, Hauswirth WW, Kay CN, Lam BL, Michaelides M, Pennesi ME, Stepien KE, Strul S, Summers CG, Carroll J. Examining Whether AOSLO-Based Foveal Cone Metrics in Achromatopsia and Albinism Are Representative of Foveal Cone Structure. Transl Vis Sci Technol.2021 May 3;10(6):22. 10. Georgiou M, Singh N, Kane T, Zaman S, Hirji N, Aboshiha J, Kumaran N, Kalitzeos A, Carroll J, Weleber RG, Michaelides M. Long-Term Investigation of Retinal Function in Patients with Achromatopsia. Invest Ophthalmol Vis Sci.2020 Sep 1;61(11):38. 11. Thiadens AA, Slingerland NW, Roosing S, et al. Genetic etiology and clinical consequences of complete and incomplete achromatopsia. Ophthalmology.2009; 116: 1984– 1989. INCORPORATION BY REFERENCE All publications, patents, and patent applications mentioned herein are hereby incorporated by reference in their entirety as if each individual publication, patent or patent application was specifically and individually indicated to be incorporated by reference. In case of conflict the present application including any definitions herein will control EQUIVALENTS Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the present invention described herein. Such equivalents are intended to be encompassed by the following claims.

INFORMAL SEQUENCE LISTING Table 1 below shows the SEQ ID NOs of the exemplary nucleic acid sequences and amino acid sequences described herein. Table 1

Claims

CLAIMS What is claimed is: 1. A method of treating a subject, comprising: (a) selecting the subject if a predetermined pattern of fundus autofluorescence (FAF) is present in an eye of the subject at baseline; and (b) administering to the subject an effective amount of a therapy suitable for treating achromatopsia (ACHM).

2. A method of selecting and treating a subject predisposed to achromatopsia (ACHM), comprising: (a) selecting the subject if a predetermined pattern of fundus autofluorescence (FAF) is present in an eye of the subject at baseline; and (b) administering to the subject an effective amount of a therapy suitable for treating achromatopsia (ACHM).

3. A method of selecting and treating a subject having achromatopsia (ACHM) that is likely to be a visual field responder, comprising: (a) selecting the subject if a predetermined pattern of fundus autofluorescence (FAF) is present in an eye of the subject at baseline; and (b) administering to the subject an effective amount of a therapy suitable for treating achromatopsia (ACHM).

4. A method of reducing, inhibiting and/or preventing one or more symptoms of achromatopsia (ACHM) in a subject, comprising: (a) selecting the subject if a predetermined pattern of fundus autofluorescence (FAF) is present in an eye of the subject at baseline; and (b) administering to the subject an effective amount of a therapy suitable for treating achromatopsia (ACHM).

5. The method of any one of the preceding claims, further comprising classifying the pattern of fundus autofluorescence (FAF) in the eye of the subject as comprising central hypoautofluorescence (grade 0), normal autofluorescence (grade 1), or mild or strong hyperautofluorescence (grade 2).

6. The method of any one of the preceding claims, wherein: (a) a pattern of FAF comprising central hypoautofluorescence (grade 0) identifies a subject that is less likely to be a visual field responder; (b) a pattern of FAF comprising normal autofluorescence (grade 1) identifies a subject that is less likely to be a visual field responder; and/or (c) a pattern of FAF comprising mild or strong hyperautofluorescence (grade 2) identifies a subject that is more likely to be a visual field responder.

7. The method of any one of the preceding claims, wherein the predetermined pattern of fundus autofluorescence (FAF) is mild or strong hyperautofluorescence (grade 2).

8. The method of any one of the preceding claims, wherein the predetermined pattern of fundus autofluorescence (FAF) in the eye of the subject is obtained prior to or at the time of administration of the therapy suitable for treating achromatopsia (ACHM).

9. The method of any one of the preceding claims, further comprising monitoring the pattern of fundus autofluorescence (FAF) in the eye of the subject for a period of time after administration of the therapy suitable for treating achromatopsia (ACHM).

10. A method of treating a subject, comprising: (a) selecting the subject if a predetermined optical coherence tomography (OCT) central outer retina morphology is present in an eye of the subject at baseline; and (b) administering to the subject an effective amount of a therapy suitable for treating achromatopsia (ACHM).

11. A method of selecting and treating a subject predisposed to achromatopsia (ACHM), comprising: (a) selecting the subject if a predetermined optical coherence tomography (OCT) central outer retina morphology is present in an eye of the subject at baseline; and (b) administering to the subject an effective amount of a therapy suitable for treating achromatopsia (ACHM).

12. A method of selecting and treating a subject having achromatopsia (ACHM) that is more likely to be a visual field responder, comprising: (a) selecting the subject if a predetermined optical coherence tomography (OCT) central outer retina morphology is present in an eye of the subject at baseline; and (b) administering to the subject an effective amount of a therapy suitable for treating achromatopsia (ACHM).

13. A method of reducing, inhibiting and/or preventing one or more symptoms of achromatopsia (ACHM) in a subject, comprising: (a) selecting the subject if a predetermined optical coherence tomography (OCT) central outer retina morphology is present in an eye of the subject at baseline; and (b) administering to the subject an effective amount of a therapy suitable for treating achromatopsia (ACHM).

14. The method of any one of claims 10-13, further comprising classifying the optical coherence tomography (OCT) central outer retina morphology in the eye of the subject as comprising central absence of ellipsoid zone (EZ) line disturbance (grade 0), the presence of EZ line disturbance (grade 1), or the presence of empty optical space (grade 2).

15. The method of claim 14, wherein: (a) an OCT central outer retina morphology comprising the central absence of ellipsoid zone (EZ) line disturbance (grade 0) identifies a subject that is more likely to be a visual field responder; (b) an OCT central outer retina morphology comprising the presence of EZ line disturbance (grade 1) identifies a subject that is more likely to be a visual field responder; and/or (c) an OCT central outer retina morphology comprising the presence of empty optical space (grade 2) identifies a subject that is less likely to be a visual field responder.

16. The method of any one of claims 10-15, wherein the predetermined optical coherence tomography (OCT) central outer retina morphology is central absence of ellipsoid zone (EZ) line disturbance (grade 0) or presence of EZ line disturbance (grade 1).

17. The method of any one of claims 10-16, wherein the predetermined optical coherence tomography (OCT) central outer retina morphology in the eye of the subject is obtained prior to or at the time of administration of the therapy suitable for treating achromatopsia (ACHM).

18. The method of any one of claims 10-17, further comprising monitoring the optical coherence tomography (OCT) central outer retina morphology in the eye of the subject for a period of time after administration of the therapy suitable for treating achromatopsia (ACHM).

19. The method of any one of the preceding claims, further comprising testing the subject for a visual field response.

20. The method of any one of the preceding claims, wherein the subject is a visual field responder.

21. The method of any one of the preceding claims, wherein the subject is suffering from achromatopsia (ACHM).

22. The method of any one of the preceding claims, wherein the subject has at least one mutation in an achromatopsia (ACHM)-associated gene selected from the group consisting of ATF6, CNGA3, CNGB3, GNAT2, PDE6C, and PDE6H.

23 The method of any one of the preceding claims, which results in the amelioration of one or more symptoms of achromatopsia (ACHM).

24. The method of any one of the preceding claims, which results in a decrease in central hyperautofluorescence, optionally, as compared to a baseline measurement.

25. The method of any one of the preceding claims, wherein the one or more symptoms of a d achromatopsia (ACHM) is selected from the group consisting of a reduced visual acuity, a pendular nystagmus, an increased sensitivity to light (photophobia), a small central scotoma, and/or a reduced or complete loss of color discrimination.

26. The method of any one of the preceding claims, which results in an improvement in visual sensitivity measured by static perimetry, optionally, as compared to a baseline measurement.

27. The method of any one of the preceding claims, which results in an improvement in light discomfort thresholds measured using an ocular photosensitivity analyzer (OPA), optionally, as compared to a baseline measurement.

28. The method of any one of the preceding claims, which results in an improvement in electrical signaling in the retina as measured by multi-focal electroretinography (mfERG), optionally, as compared to a baseline measurement.

29. The method of any one of claims 26-28, wherein the improvement in visual sensitivity, light discomfort thresholds, and/or electrical signaling in the retina is maintained over a period of time comprising at least about 1 month or more.

30. The method of any one of claims 26-29, wherein the improvement in visual sensitivity, light discomfort thresholds, and/or electrical signaling in the retina is maintained for the lifetime of the subject.

31. The method of any one of the preceding claims, wherein the therapy suitable for treating achromatopsia (ACHM) comprises a gene therapy.

32. The method of claim 31, wherein the gene therapy comprises a nucleic acid sequence encoding an achromatopsia (ACHM)-associated gene.

33. The method of claim 32, wherein the achromatopsia (ACHM)-associated gene is selected from the group consisting of ATF6, CNGA3, CNGB3, GNAT2, PDE6C, and PDE6H.

34. The method of claim 32 or 33, wherein the nucleic acid sequence is codon optimized for mammalian expression.

35. The method of any one of claims 32-34, wherein: (i) the nucleic acid sequence comprises SEQ ID NO: [1], or a sequence at least 85% identical to SEQ ID NO: [1]; or (i) the nucleic acid sequence comprises SEQ ID NO: [150], or a sequence at least 85% identical to SEQ ID NO: [150].

36. The method of any one of claims 32-35, wherein the nucleic acid sequence is a cDNA sequence.

37. The method of any one of claims 32-36, wherein the nucleic acid sequence is operably linked to a promoter.

38. The method of claim 37, wherein the promoter comprises a PR1.7 promoter (SEQ ID NO: 2).

39. The method of any one of claims 32-38, wherein the nucleic acid sequence further comprises an operably linked minimal regulatory element.

40. The method of claim 39, wherein the minimal regulatory element comprises a polyadenylation site, splicing signal sequences, and/or AAV inverted terminal repeats.

41. The method of claim 40, wherein the nucleic acid sequence further comprises an operably linked polyadenylation signal (pA), optionally, a SV(40) polyA.

42. The method of any one of claims 31-41, wherein the gene therapy comprises a vector.

43. The vector of claim 42, wherein the vector is an adeno-associated viral (AAV) vector.

44. The vector of claim 43, wherein the serotype of the capsid sequence and the serotype of the ITRs of said AAV vector are independently selected from the group consisting of AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10, AAV11, and AAV12.

45. The vector of claim 44, wherein the capsid sequence is a mutant capsid sequence.

46. The method of claim 42-45, wherein the vector comprises a recombinant adeno- associated (rAAV) expression vector.

47. The method of any one of claims 42-46, wherein the vector comprises a transgene expression cassette comprising a promoter; an achromatopsia (ACHM)-associated gene nucleic acid; and minimal regulatory elements.

48. The method of claim 47, wherein the minimal regulatory elements comprise a polyadenylation site, splicing signal sequences, and/or AAV inverted terminal repeats.

49. The method of claim 48, wherein the minimal regulatory elements comprise a poly adenylation (SV40 poly A) signal and flanking AAV inverted terminal repeats (ITR).

50. The method of any one of claims 44-49, wherein the serotype of the capsid sequence and the serotype of the ITRs of said AAV vector are independently selected from the group consisting of AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10, AAV11, and AAV12.

51. The method of claim 50, wherein the serotype of the capsid sequence is AAV2.

52. The method of claim 50, wherein the capsid sequence is a mutant capsid sequence.

53. The method of any one of claims 42-53, wherein the vector is administered to the subject subretinally.