Methods and compositions for treating eye conditions

Abstract

This disclosure provides recombinant nucleic acids comprising one or more polynucleotides encoding polypeptides; viruses comprising said recombinant nucleic acids; compositions and formulations comprising said recombinant nucleic acids and / or viruses; methods of use thereof (for example, for the treatment of one or more conditions or diseases of the eye); and articles or kits for the manufacture thereof. TIFF2026515744000019.tif54128

Description

Technical Field

[0001] Cross - Reference to Related Applications This application claims the benefit of priority of U.S. Provisional Patent Application No. 63 / 459,102, filed on April 13, 2023, U.S. Provisional Patent Application No. 63 / 460,948, filed on April 21, 2023, and U.S. Provisional Patent Application No. 63 / 593,085, filed on October 25, 2023, the contents of which are incorporated herein by reference in their entirety.

[0002] Sequence Listing Information The sequence listing related to this application is submitted in electronic form via the Patent Center, and its entirety is incorporated herein by reference. The name of the file containing the sequence listing is 2401989.xml. The file size is 1,738,822 bytes, and the file was created on April 12, 2024.

[0003] Field of the Invention This disclosure relates, in part, to recombinant nucleic acids comprising one or more polynucleotides encoding polypeptides, viruses containing the same, their pharmaceutical compositions and formulations, and methods of using them (e.g., for treating one or more conditions or diseases of the eye).

Background Art

[0004] Background Eye conditions, vision loss, eye diseases, and / or visual impairments pose a significant economic burden with an estimated annual cost of approximately $139 billion in the United States. Despite significant advances in clinical care and treatment methods, more effective treatment options are still needed.

[0005] All references cited herein, including patent applications, patent publications, non - patent literature, and NCBI / UniProtKB / Swiss - Prot accession numbers, are incorporated herein by reference in their entirety as if each individual reference were specifically and individually indicated to be incorporated by reference. [Overview of the project]

[0006] overview To address these and other needs, the Specified Provisions provide recombinant nucleic acids encoding one or more polypeptides (e.g., recombinant herpesvirus genomes), viruses (e.g., herpesviruses) containing recombinant nucleic acids (e.g., recombinant herpesvirus genomes), pharmaceutical compositions and formulations, pharmaceuticals, and / or methods of administration in subjects where such needs exist (e.g., useful for treating eye conditions or diseases).

[0007] Accordingly, certain aspects of this disclosure relate to recombinant herpesvirus genomes comprising one or more polynucleotides encoding polypeptides. In some embodiments, the recombinant herpesvirus genome comprises two or more polynucleotides encoding polypeptides. In some embodiments, the recombinant herpesvirus genome is replication-capable. In some embodiments, the recombinant herpesvirus genome is replication-deficient. In some embodiments, which may be combined with any of the embodiments, the recombinant herpesvirus genome comprises one or more polynucleotides encoding polypeptides within one or more viral loci. In some embodiments, which may be combined with any of the embodiments, the recombinant herpesvirus genome is selected from recombinant herpes simplex virus genome, recombinant varicella-zoster virus genome, recombinant human cytomegalovirus genome, recombinant herpesvirus 6A genome, recombinant herpesvirus 6B genome, recombinant herpesvirus 7 genome, Epstein-Barr virus genome, recombinant Kaposi's sarcoma-associated herpesvirus genome, and any combination or derivative thereof.

[0008] In some embodiments that can be combined with any of the above embodiments, the recombinant herpesvirus genome is a recombinant herpes simplex virus genome. In some embodiments, the recombinant herpes simplex virus genome is a recombinant herpes simplex virus type 1 (HSV-1) genome, a recombinant herpes simplex virus type 2 (HSV-2) genome, or any combination or derivative thereof. In some embodiments, the recombinant herpes simplex virus genome is a recombinant HSV-1 genome.

[0009] In some embodiments that may be combined with any of the above embodiments, the recombinant herpes simplex virus genome is engineered to reduce or eliminate the expression of one or more herpes simplex virus genes (e.g., one or more virulent herpes simplex virus genes). In some embodiments that may be combined with any of the above embodiments, the recombinant herpes simplex virus genome includes an inactivating mutation. In some embodiments, the inactivating mutation is located in the herpes simplex virus gene. In some embodiments, the inactivating mutation is a deletion of at least a portion of the coding sequence of the herpes simplex virus gene. In some embodiments, the inactivating mutation is a deletion of the coding sequence of the herpes simplex virus gene. In some embodiments, the herpes simplex virus gene is selected from infecting cell protein (ICP) 0 (one or both copies), ICP4 (one or both copies), ICP22, ICP27, ICP47, thymidine kinase (tk), long unique region (UL) 41, and UL55. In some embodiments that can be combined with any of the above embodiments, the recombinant herpes simplex virus genome includes an inactivating mutation in one or both copies of the ICP4 gene. In some embodiments that can be combined with any of the above embodiments, the recombinant herpes simplex virus genome includes an inactivating mutation in the ICP22 gene. In some embodiments that can be combined with any of the above embodiments, the recombinant herpes simplex virus genome includes an inactivating mutation in the UL41 gene. In some embodiments that can be combined with any of the above embodiments, the recombinant herpes simplex virus genome includes an inactivating mutation in one or both copies of the ICP0 gene. In some embodiments that can be combined with any of the above embodiments, the recombinant herpes simplex virus genome includes an inactivating mutation in the ICP27 gene. In some embodiments that can be combined with any of the above embodiments, the recombinant herpes simplex virus genome includes an inactivating mutation in the UL55 gene. In some embodiments that can be combined with any of the above embodiments, the recombinant herpes simplex virus genome does not include an inactivating mutation in the ICP47 gene. In some embodiments, the recombinant herpes simplex virus genome does not contain inactivating mutations in either one or both copies of the ICP34.5 gene.In some embodiments that may be combined with any of the above embodiments, the recombinant herpes simplex virus genome does not contain an inactivating mutation in the UL36 gene.

[0010] In some embodiments that can be combined with any of the above embodiments, the recombinant herpes simplex virus genome includes one or more polynucleotides encoding a polypeptide within one or more viral loci. In some embodiments that can be combined with any of the above embodiments, the recombinant herpes simplex virus genome includes one or more polynucleotides encoding a polypeptide within one or both loci of the ICP4 viral locus. In some embodiments that can be combined with any of the above embodiments, the recombinant herpes simplex virus genome includes one or more polynucleotides encoding a polypeptide within the ICP22 viral locus. In some embodiments that can be combined with any of the above embodiments, the recombinant herpes simplex virus genome includes one or more polynucleotides encoding a polypeptide within the UL41 viral locus. In some embodiments that can be combined with any of the above embodiments, the recombinant herpes simplex virus genome includes one or more polynucleotides encoding a polypeptide within one or both loci of the ICP0 viral locus. In some embodiments that can be combined with any of the above embodiments, the recombinant herpes simplex virus genome includes one or more polynucleotides encoding a polypeptide within the ICP27 viral locus. In some embodiments that may be combined with any of the above embodiments, the recombinant herpes simplex virus genome includes one or more polynucleotides encoding a polypeptide within the UL55 viral locus.

[0011] In some embodiments that can be combined with any of the above embodiments, the polypeptide is a human polypeptide. In some embodiments that can be combined with any of the above embodiments, the polypeptide is a steryl α-motif domain-containing protein 11, nephrocystin-4, espin, nicotinamide / nicotinic acid mononucleotide adenylyltransferase 1, mitofusin-2, ER membrane protein complex subunit 1, phospholipase A2 group V, dehydrodritil diphosphate synthase complex subunit, palmitoyl protein thioesterase 1, extra-long chain fatty acid elongation protein 1, protein O-linked mannose β-1, 2-N-acetylglucosaminyltransferase 1, retinoid isomerohydrolase, retina-specific phospholipid transport ATPase, collagen α-1(XI), guanine nucleotide-binding protein G(t) subunit α-2, chloride channel CLIC-like protein 1, DNA damage-modulating autophagy modulator protein 2, U4 / U6 nuclear small ribonucleoprotein Prp3, α-endosulfin, semaphorin-4A, cyclic AMP-dependent transcription factor ATF-6α, hemisentin-1, complement factor H, clamstan Protein homolog 1, adiponectin receptor protein 1, protein RD3, serine / threonine-protein kinase Nek2, feline leukemia virus subgroup C receptor-related protein 1, Usherin, serologically defined colon cancer antigen 8, olfactory receptor 2W3, NBAS subunit of NRZ tethering factor complex, cytoplasmic carboxypeptidase-like protein 5, zinc finger protein 513, flagellar transport protein 172 homolog, photoreceptor ciliary actin regulator, EGF-containing fibrinoid cells Extramatrix protein 1 / TLE family member 5, protein FAM161A, WD repeat-containing planar cell polarity effector protein Fritz homolog, centrosome-related protein ALMS1, U5 nuclear small ribonucleoprotein 200kDa helicase, metal transporter CNNM4, cyclic nucleotide gate cation channel α-3, nephrocystin-1, tyrosine-protein kinase Mer, Valday-Beedl syndrome 5 protein, ceramide kinase-like protein, neurogenic differentiation factor 1, transmembrane protein 237,Inward-rectifying potassium channel 13, S-arrestin, secreted phosphoprotein 24, CCA tRNA nucleotidyltransferase 1 (mitochondrial), sodium bicarbonate cotransporter 3, leucine zipper transcription factor-like protein 1, guanine nucleotide-binding protein G(t) subunit α-1, 3-prime repair exonuclease 1, MAP kinase-activated protein kinase 3, ataxin-7, vitamin K-dependent protein S, ADP ribosylation factor-like protein 6, photoreceptor matrix proteoglycan 2, IQ calmodulin-binding motif-containing protein 1, rhodopsin, nephrocystin-3, clarine-1, putative cationic amino acid transporter / solute carrier family 7 member 14, choline phosphate cytidylyltransferase A, 19kDa centrosome protein, rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit β, Wolfram Protein 1, homeobox protein HMX1, Ras-related protein Rab-28, coiled-coil C2 domain-containing protein 2A, prominin-1, adhesion-type G protein-coupled receptor A3, death domain-containing protein 1, WD repeat-containing protein 19, cGMP gate cation channel α-1, CDGSH iron-sulfur domain-containing protein 2, microsomal triglyceride transport protein large subunit, leucine-rich repeat, immunoglobulin-like domain / transmembrane domain-containing protein 3, Valday-Beedl syndrome protein 7, Valday-Beedl syndrome protein 12, major promoter superfamily domain-containing protein 8, serine / threonine-protein kinase PLK4, lecithin retinol acyltransferase, Toll-like receptor 3, cytochrome P450 4V2, Spliceosome-related protein CWC27 homolog, Centrosome protein POC5, Versican core protein, Adhesion-type G protein-coupled receptor V1, COUP transcription factor 1, Mitochondrial outer membrane protein SLC25A46, Catenin α-1, Histidine--tRNA ligase (cytoplasm), Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit α, Metabotropic glutamate receptor 6, Serine / threonine-protein kinase MAK, Complement C2, Complement factor B, Tubby-related protein 1,Guanylyl cyclase activating protein 1, guanylyl cyclase activating protein 2, peripherin-2, photoreceptor matrix proteoglycan 1, iShat homolog protein, collagen α-1(IX) chain, regulatory synaptic membrane exocytosis protein 1, level cylin, extra-long chain fatty acid elongation protein 4, PR domain zinc finger protein 13, reticulon-4 interacting protein 1 (mitochondria), jubelin, peroxisome targeting signal 2 receptor, CCR4-NOT transcription complex subunit 9, aromatic hydrocarbon receptor, Kelch-like protein 7, retinitis pigmentosa protein 9, protein PTHB 1, peroxisome ATPase PEX 1, tetraspanin-1 2, inosine-5'-monophosphate dehydrogenase 1, shortwave sensitive opsin 1, UPF0606 protein KIAA1549, retinitis pigmentosa-like protein 1, disintegrin / metalloproteinase domain-containing protein 9, heparan-α-glucosaminid N-acetyltransferase, oxygen regulatory protein 1, α-tocopherol transport protein, centrosome / spindle pole-related protein 1, dynamin-like 120kDa protein (mitochondrial), peroxisome formation factor 2, cyclic nucleotide gate cation channel β-3, ciliary / flagellar-related protein 418, growth / differentiation factor 6, regulatory synaptic membrane exocytosis protein 2, voltage-gated potassium channel superfamily V member 2, E3 ubiquitin protein ligase Topors, 78kDa centrosome protein, inversin, U4 / U6 nuclear small ribonucleotide protein Prp4, Warlin, E3 ubiquitin protein ligase TRIM32, Toll-like receptor 4, cytoplasmic dynein 2 intermediate chain 2, programmed cell death protein 2, exosome complex component RRP4, phosphatidylinositol polyphosphate 5-phosphatase type IV, phytanoyl-CoA dioxygenase (peroxisome), acyl-CoA binding domain-containing protein, protocadherin-15, retinol-binding protein 3, DNA excision repair protein ERCC-6, hexokinase-1, cadherin-23, cadherin-related family member 1, RPE retinal G protein-coupled receptor, kinesin-like protein KIF11,Retinol-binding protein 4, cone cGMP-specific 3',5'-cyclic phosphodiesterase subunit α, pair-box protein Pax-2, PDZ domain-containing protein 7, ADP-ribosylation factor-like protein 3, BBSome-interacting protein 1, age-related macular degeneration-sensitive protein 2, serine protease HTRA1, ornithine aminotransferase (mitochondrial), zinc finger protein 408, Tubby protein homolog, transcription enhancer factor TEF-1, harmonin, transmembrane protein 216, bethroffin-1, isoaspartyl peptidase / L -Asparaginase, rod extrasegmental membrane protein 1, Valday-Beedl syndrome 1 protein, calcium-binding protein 4, low-density lipoprotein receptor-related protein 5, calpain-5, atypical myosin-VIIa, transmembrane protein 126A, frizzled-4, cytoplasmic dynein 2 light intermediate chain 1, 164kDa centrosome protein, complement C1q tumor necrosis factor-related protein 5, membrane frizzled-related protein, voltage-gated calcium channel subunit α-2 / δ-4, guanine nucleotide-binding protein G(I) / G(S) / G(T) subunit β-3, retinal cone rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit γ, collagen α-1(II) chain, matrix metalloproteinase-19, retinol dehydrogenase 5, T complex protein 1 subunit β, Balday-Beedl syndrome 10 protein, 290kDa centrosome protein, POC1 centriole protein homolog B, mevalonate kinase, flagellar transport protein 81 homolog, mitochondrial translation termination factor in rescue, intrinsic membrane protein 2B, retinoblastoma-associated protein, RCC1 and BTB domain Protein 1, rhodopsin kinase GRK1, X-linked retinitis pigmentosa GTPase regulatory factor interaction protein 1, neuroretinal specific leucine zipper protein, homeobox protein OTX2, retinol dehydrogenase 11, retinol dehydrogenase 12, tubulin polyglutamylase TTLL5, spermatogenesis-related protein 7, tetratricopeptide repeat protein 8, fibrin-5, transient receptor potential cation channel subfamily M member 1, γ-tubulin complex component 4,Sodium / potassium / calcium exchanger 1, photoreceptor-specific nuclear receptor, Valday-Beedl syndrome 4 protein, calcium and integrin-binding family member 2, retinaldehyde-binding protein 1, N-acetylglucosamine-1-phosphotransferase subunit γ, flagellar transport protein 140 homolog, clatherin-related protein 1, ATP-binding cassette subfamily member C 6, ketimine reductase μ-crystallin, battenin, zinc finger protein 423, protein phantom, Valday-Beedl syndrome 2 protein, ADP-ribosylation factor-like protein 2-binding protein, cyclic nucleotide gate cation channel β-1, cadherin-3, premRNA spread The following are related to retinal rod rhodopsin-sensitive cGMP: ATP-dependent RNA helicase PRP16, disintegrin metalloproteinase A with thrombospondin motif 18, solute carrier family 38 member 8, retinal guanylyl cyclase 1, premRNA processing splicing factor 8, aromatic hydrocarbon interacting protein-like 1, membrane-bound phosphatidylinositol transport protein 3, protein unc-119 homolog A, putative G protein-coupled receptor 179, tectonic-like complex member MKS1, carbonic anhydrase 4, G protein signaling regulator 9, aryl sulfatase G, premRNA splicing regulator USH1G, photoreceptor disk component PRCD, phascin-2, and retinal rod rhodopsin-sensitive cGMP. 3',5'-cyclic phosphodiesterase subunit γ, laminin subunit α-1, AFG3-like protein 2, cone-rod homeobox protein, receptor expression-enhancing protein 6, anterior retinal nerve fold homeobox protein 2, complement C3, Rho guanine nucleotide exchange factor 18, patatin-like phospholipase domain-containing protein 6, G protein signaling regulator 9 binding protein, optic nerve atrophy protein 3, U4 / U6 nuclear small ribonucleoprotein Prp31, isocitrate dehydrogenase [NAD] subunit β (mitochondria), pantothenate kinase 2 (mitochondria), protein jagged-1, molecular chaperone MKKS, centrosome protein kizuna, lysophosphatidylserine lipase ABHD12,Kinesin-like protein KIF3B, centrioles-related protein CEP250, premRNA processing factor 6, ciliary / flagellar-related protein 410, dynamin-1-like protein, metalloproteinase inhibitor 3, flagellar transport protein 27 homolog, fibrin-1, MIEF1 upstream open reading frame protein, aconitate hydratase (mitochondria), γ-tubulin complex component 6, centrioles / centrosome satellite proteins, retinosuxin, protein XRP2, dystrophin, X-linked retinitis pigmentosa GTPase regulator, nictaropine, Xaa-prodipeptidase, noline, voltage-gated L-type calcium channel subunit α-1F, phosphoglycerate kinase 1, Rab protein geranylgeranyltransferase component A1, mitochondrial import inner membrane transport enzyme subunit Tim8 A, ribose phosphate pyrophosphokinase 1, long-wave sensitive opsin 1, medium-wave sensitive opsin 1, short-wave sensitive opsin 1, transcription factor A (mitochondria), NADH ubiquinone oxidoreductase chain 1, NADH ubiquinone oxidoreductase chain 2, NADH ubiquinone oxidoreductase chain 3, NADH ubiquinone oxidoreductase chain 4L, NADH ubiquinone oxidoreductase chain 4, NADH ubiquinone oxidoreductase chain 5, NADH ubiquinone oxidoreductase chain 6, ATP synthase subunit a, ATP synthase protein 8, cytochrome c oxidizer, Subunit 1, cytochrome c oxidase subunit 3, cytochrome b, leucine--tRNA ligase (mitochondrial), indiscriminate glutamyl-tRNA synthetase EARS2 (mitochondrial), lysine--tRNA ligase, histidine--tRNA ligase (mitochondrial), serine--tRNA ligase (mitochondrial), putative proline--tRNA ligase (mitochondrial), cyanocobalamin reductase / alkylcobalamin dealkylase, POU domain, class 3, transcription factor 4, ribosomal protein S6 kinase α-6, ciliation and planar polarity effector 1, Mecke Phosphorus, TRAF3-interacting protein 1, flagellar transport protein 74 homolog, S-phase cyclin A-related protein in the endoplasmic reticulum, sodium channel and clathrin linker 1, protein TALPID3, tectonic-2, ADP-ribosylation factor-like protein 13B, B9 domain-containing protein 1, B9 domain-containing protein 2, C2 domain-containing protein 3, 41kDa centrosome protein, 104kDa centrosome protein, 120kDa centrosome protein, flagellar transport protein 172 homolog, katanin-interacting protein, kinesin-like protein KIF7, retinal rod rhodopsin-sensitive cGMP The group selected consists of 3',5'-cyclic phosphodiesterase subunit δ, tectonic-1, tectonic-3, transmembrane protein 107, transmembrane protein 138, transmembrane protein 231, tetratricopeptide repeat protein 21B, nuclear receptor ROR-α, β nerve growth factor, collagen α-2(VIII) chain, solute carrier family 4 member 11, zinc finger E-box linked homeobox 1, keratin type II cuticle Hb3, keratin type I cytoskeleton 12, transforming growth factor-β-inducing protein ig-h3, tumor-associated calcium signaling factor 2, carbohydrate sulfotransferase 6, gelzolin, UbiA prenyltransferase domain-containing protein 1, decorin, 1-phosphatidylinositol 3-phosphate 5-kinase, transcription factor Ovo-like 2, and Grainyhead-like protein 2 homolog.

[0012] In some embodiments that can be combined with any of the above embodiments, the recombinant herpesvirus genome, when introduced into target cells, exhibits reduced cytotoxicity compared to the corresponding wild-type herpesvirus genome. In some embodiments, the target cells are human cells. In some embodiments, the target cells are eye cells. In some embodiments, the target cells are corneal epithelial cells. In some embodiments, the target cells are retinal cells. In some embodiments, the target cells are retinal pigment epithelial cells. In some embodiments, the target cells are photoreceptors.

[0013] Other aspects of this disclosure relate to herpesviruses comprising any of the recombinant herpesvirus genomes described herein. In some embodiments, the herpesvirus is replication-capable. In some embodiments, the herpesvirus is replication-deficient. In some embodiments, which may be combined with any of the embodiments, the herpesvirus is not oncolytic. In some embodiments, which may be combined with any of the embodiments, the herpesvirus is a pseudotyped virus. In some embodiments, which may be combined with any of the embodiments, the herpesvirus is not a pseudotyped virus. In some embodiments, which may be combined with any of the embodiments, the herpesvirus is not a pseudotyped oncolytic virus. In some embodiments, which may be combined with any of the embodiments, the herpesvirus has reduced cytotoxicity compared to the corresponding wild-type herpesvirus. In some embodiments that can be combined with any of the above embodiments, the herpesvirus is selected from herpes simplex virus, varicella-zoster virus, human cytomegalovirus, herpesvirus 6A, herpesvirus 6B, herpesvirus 7, Epstein-Barr virus, Kaposi's sarcoma-associated herpesvirus, and any combination or derivative thereof. In some embodiments that can be combined with any of the above embodiments, the herpesvirus is herpes simplex virus. In some embodiments, the herpes simplex virus is not oncolytic. In some embodiments, the herpes simplex virus is HSV-1, HSV-2, or any combination or derivative thereof. In some embodiments, the herpes simplex virus is HSV-1. In some embodiments, HSV-1 is not oncolytic.

[0014] Other aspects of this disclosure relate to pharmaceutical compositions comprising any of the recombinant herpesvirus genomes and / or recombinant herpesviruses described herein, and a pharmaceutically acceptable carrier or excipient. In some embodiments that can be combined with any of the embodiments, the pharmaceutical composition is suitable for ocular, subretinal, intraocular, intravitreous, topical, subcutaneous, subconjunctival, sub-Tenon, sub-Tenon's capsule, intrachoracic, retrobulbar, systemic, parenteral, periocular, juxtascleral, anterior juxtascleral, posterior juxtascleral, oral, periocular, or choroidal administration. In some embodiments that can be combined with any of the embodiments, the pharmaceutical composition comprises a phosphate buffer. In some embodiments that can be combined with any of the embodiments, the pharmaceutical composition comprises glycerol. In some embodiments that can be combined with any of the embodiments, the pharmaceutical composition comprises a lipid carrier. In some embodiments that can be combined with any of the embodiments, the pharmaceutical composition comprises a nanoparticle carrier.

[0015] Other aspects of this disclosure relate to the use of any of the recombinant nucleic acids (e.g., recombinant herpesvirus genomes), recombinant viruses (e.g., recombinant herpesviruses), and / or pharmaceutical compositions described herein as pharmaceuticals.

[0016] Other aspects of this disclosure relate to the use of any of the recombinant nucleic acids (e.g., recombinant herpesvirus genomes), recombinant viruses (e.g., recombinant herpesviruses), and / or pharmaceutical compositions described herein in therapeutic applications.

[0017] Other aspects of this disclosure relate to the use of any of the recombinant nucleic acids (e.g., recombinant herpesvirus genomes), recombinant viruses (e.g., recombinant herpesviruses), and / or pharmaceutical compositions described herein in the preparation of pharmaceuticals for treating eye conditions or diseases.

[0018] Other aspects of this disclosure relate to methods for expressing, enhancing, increasing, strengthening, and / or supplementing polypeptide levels in one or more cells of a subject, comprising administering to the subject an effective amount of any of the recombinant herpesviruses and / or pharmaceutical compositions described herein. In some embodiments, the one or more cells are one or more cells of an eye. In some embodiments that may be combined with any of the above embodiments, the subject is human. In some embodiments that may be combined with any of the above embodiments, the herpesvirus or pharmaceutical composition is administered by injection, by injection into the eye, by subretinal injection, by intraocular injection, by intravitreous injection, by suprachoroidal injection, intraocular, intravitreous, topically, subcutaneously, subconjunctivally, subtenon, intraanterior chamber, retroocular, systemically, parenterally, periocularly, near the sclera, near the anterior sclera, near the posterior sclera, orally, periocularly, or onto the choroid.

[0019] Other aspects of this disclosure relate to methods for providing preventive, mitigating, or therapeutic relief of one or more signs or symptoms of an ocular condition or disease in a subject in need, comprising administering to the subject an effective amount of any recombinant herpesvirus and / or pharmaceutical composition described herein. In some embodiments, the ocular condition or disease is retinitis pigmentosa, recessive retinitis pigmentosa, severe recessive retinitis pigmentosa, dominant retinitis pigmentosa, dominant retinitis pigmentosa with choroidal lesions, recessive retinitis pigmentosa with parapeteropallor preservation of RPE (PPRPE), recessive retinitis pigmentosa with posterior column ataxia (PCARP), recessive retinitis pigmentosa with microcytosis, symptomatic recessive retinitis pigmentosa, recessive symptomatic disease with retinitis pigmentosa, non-symptomatic recessive retinitis pigmentosa, non-symptomatic dominant retinitis pigmentosa, and symptomatic dominant retinitis pigmentosa. Juvenile recessive retinitis pigmentosa, recessive retinitis pigmentosa and intellectual disability, recessive retinitis pigmentosa with macular degeneration, severe early-onset recessive retinitis pigmentosa, recessive retinitis pigmentosa and bone malformations, recessive retinitis pigmentosa and skeletal abnormalities, dominant retinitis pigmentosa with sensorineural hearing loss, recessive retinitis pigmentosa with hearing loss, recessive retinitis pigmentosa with hearing loss and additional disability, recessive retinitis pigmentosa with vitreous degeneration, early-onset recessive retinitis pigmentosa with macular defect, X-linked retinitis pigmentosa, recessive X-linked retinitis pigmentosa, dominant X X-linked retinitis pigmentosa, severe X-linked retinitis pigmentosa, X-linked retinitis pigmentosa with intellectual disability, X-linked retinitis pigmentosa with myopathy, Valday-Beedl-like retinitis pigmentosa, Valday-Beedl-like recessive retinitis pigmentosa, bigenic retinitis pigmentosa, bigenic retinitis pigmentosa with retinal outer segment membrane protein 1, bigenic retinitis pigmentosa with PRPH2, recessive retinitis pigmentosa with early macular lesions, recessive hearing loss without retinitis pigmentosa, recessive congenital hearing loss without retinitis pigmentosa, recessive retina Pigmentous degeneration and recessive ataxia, recessive retinitis pigmentosa and dominant ataxia, mitochondrial retinitis pigmentosa, mitochondrial retinitis pigmentosa with developmental and neurological abnormalities, mitochondrial retinitis pigmentosa with progressive sensorineural hearing loss, mitochondrial retinitis pigmentosa with hearing loss and neurological abnormalities, autosomal dominant retinitis pigmentosa, asymptomatic autosomal dominant retinitis pigmentosa, autosomal recessive retinitis pigmentosa, asymptomatic autosomal recessive retinitis pigmentosa, retinal pigment epithelium (RPE), recessive RPE, dominant RPE, recessive RPE degeneration,Dominant RPE degeneration, ataxia, recessive ataxia, dominant ataxia, Senior Loken syndrome, recessive Senior Loken syndrome, dominant Senior Loken syndrome, nephronoplasia, recessive nephronoplasia, dominant nephronoplasia, adolescent recessive nephronoplasia, ciliopathy-associated recessive nephronoplasia, juvenile nephronoplasia, juvenile recessive nephronoplasia, juvenile dominant nephronoplasia, Usher syndrome, Usher syndrome type I, Usher syndrome type II, Usher syndrome type III, recessive Usher syndrome, atypical recessive Usher syndrome, dominant Usher syndrome, type II recessive Usher syndrome, type 2a recessive Usher syndrome Syndrome, type 3 recessive Usher syndrome, type 3-like recessive Usher syndrome, atypical recessive Usher syndrome, type 1 recessive Usher syndrome, type 1b recessive Usher syndrome, type 1d recessive Usher syndrome, type 1f recessive Usher syndrome, type 1J recessive Usher syndrome, type 1k recessive Usher syndrome, bigenic Usher syndrome with CDH23, bigenic Usher syndrome with PCDH15, Acadian recessive Usher syndrome, recessive atypical Usher syndrome (USH3-like), Leber's congenital amaurosis, recessive Leber's congenital amaurosis, dominant Leber's Bell congenital amaurosis, de novo Leber congenital amaurosis, dominant Leber congenital amaurosis and pituitary dysfunction, recessive Leber congenital amaurosis with myopathy, recessive Leber congenital amaurosis with severe childhood retinal dystrophy, mitochondrial Leber hereditary optic neuropathy, Leber hereditary optic neuropathy, optic nerve atrophy, recessive optic nerve atrophy, dominant optic nerve atrophy, optic nerve atrophy with ataxia, recessive optic nerve atrophy with ataxia, dominant optic nerve atrophy with ataxia, recessive optic nerve atrophy with ataxia, recessive optic nerve atrophy with ataxia and 3-methylglutaconic aciduria, cataract, dominant optic nerve with ataxia and anreflexia Atrophy, Kjer-type dominant optic atrophy, dominant optic atrophy with sensorineural hearing loss, recessive cerebellar degeneration with optic atrophy, optic atrophy with anesthesia-dystonia syndrome, X-linked optic atrophy with anesthesia-dystonia syndrome, retinal dystrophy, recessive retinal dystrophy, dominant retinal dystrophy, hereditary retinal dystrophy, early-onset recessive retinal dystrophy, recessive symptomatic retinal dystrophy, recessive asymptomatic retinal dystrophy, recessive symptomatic and asymptomatic retinal dystrophy, recessive optic atrophy and retinal dystrophy, recessive retinal dystrophy and obesity,Recessive retinal dystrophy and cerebellar dysplasia, symptomatic recessive optic atrophy and retinal dystrophy, dominant retinal dystrophy with iris defects, ciliopathy spectrum including retinal dystrophy, recessive ciliopathy spectrum including retinal dystrophy, dominant ciliopathy spectrum including retinal dystrophy, dominant optic atrophy with neuropathy and myopathy, dominant optic atrophy with intellectual disability and developmental delay, symptomatic optic atrophy, asymptomatic optic atrophy, recessive asymptomatic optic atrophy Atrophy, dominant asymptomatic optic nerve atrophy, recessive symptomatic optic nerve atrophy, dominant symptomatic optic nerve atrophy, Charcot-Marie-Tooth disease, recessive Charcot-Marie-Tooth disease, dominant Charcot-Marie-Tooth disease, benign spotted retina, recessive benign spotted retina, dominant benign spotted retina, symptomatic retinopathy, recessive symptomatic retinopathy, dominant symptomatic retinopathy, Batten disease, recessive Batten disease, dominant Batten disease, recessive Batten disease (neuroceroid lipofuscinopathy type 3), juvenile recessive Batten disease (neuroceroid lipofuscinopathy Macular dystrophy (type 3), neuronal ceroid lipofuscinosis, recessive neuronal ceroid lipofuscinosis, recessive neuronal ceroid lipofuscinosis type 1, dominant neuronal ceroid lipofuscinosis, Stargart disease, recessive Stargart disease, dominant Stargart disease, juvenile Stargart disease, late-onset Stargart disease, Stargart-like macular dystrophy, recessive Stargart-like macular dystrophy, dominant Stargart-like macular dystrophy, macular dystrophy, recessive macular dystrophy, early-onset macular dystrophy Dystrophy, adult-onset macular dystrophy, early-onset recessive macular dystrophy, adult-onset recessive macular dystrophy, early adult-onset recessive macular dystrophy, juvenile recessive macular dystrophy with hypotrichosis, dominant macular dystrophy, late-onset dominant macular dystrophy, dominant macular dystrophy with lens zonules, bullseye dominant macular dystrophy, butterfly-shaped dominant macular dystrophy, age-related dominant macular dystrophy, benign concentric annular dominant macular dystrophy, vitelloid recessive macular dystrophy, vitelloid dominant macular dystrophy, atypical vitelloid dominant macular dystrophy, dominant adult-type vitelloid macular dystrophy, Stargard-type dominant macular dystrophy, Stargard-type dominant macular dystrophy,North Carolina dominant macular dystrophy, North Carolina-like dominant macular dystrophy, North Carolina-like dominant macular dystrophy with progressive sensorineural hearing loss, cystoid dominant macular dystrophy, Best-type dominant macular dystrophy, occult macular dystrophy, recessive occult macular dystrophy, dominant occult macular dystrophy, age-related familial macular dystrophy, X-linked atrophic macular dystrophy, recessive X-linked atrophic macular dystrophy, dominant X-linked atrophic macular dystrophy, mitochondrial macular pattern dystrophy with type II diabetes and hearing loss Rophy, yellow spot fundus, recessive yellow spot fundus, dominant yellow spot fundus, rod dystrophy, recessive rod dystrophy, dominant rod dystrophy, cone dystrophy, recessive cone dystrophy, dominant cone dystrophy, recessive cone dystrophy with supernormal rod electroretinogram, early-onset recessive cone dystrophy, late-onset recessive cone dystrophy, cone dystrophy 1, X-linked cone dystrophy 1, cone dystrophy 2, progressive cone dystrophy 2, X-linked progressive cone dystrophy 2, delayed cone adaptation, recessive delayed cone adaptation, dominant delayed cone adaptation, cone rod Rod-condylophysical dystrophy, recessive rod-condylophysical dystrophy, dominant rod-condylophysical dystrophy, solitary rod-condylophysical dystrophy, progressive rod-condylophysical dystrophy, X-linked rod-condylophysical dystrophy, X-linked progressive rod-condylophysical dystrophy, progressive dominant rod-condylophysical dystrophy, rod-condylophysical dystrophy and enamel hypoplasia syndrome, recessive rod-condylophysical dystrophy and enamel hypoplasia syndrome, dominant rod-condylophysical dystrophy and enamel hypoplasia syndrome, recessive rod-condylophysical dystrophy with internal retinopathy, recessive rod-condylophysical dystrophy with bone disease, congenital disorders Symptomatic non-progressive recessive pyramidal-rodylosis, recessive pyramidal-rodylosis with hearing loss, recessive pyramidal-rodylosis with psychomotor retardation, recessive pyramidal and pyramidal-rodylosis, pyramidal-rodylosis synaptic disease, congenital pyramidal-rodylosis synaptic disease, recessive congenital pyramidal-rodylosis synaptic disease, dominant congenital pyramidal-rodylosis synaptic disease, rod-pyramidal dystrophy, recessive rod-pyramidal dystrophy, dominant rod-pyramidal dystrophy, early-onset recessive rod-pyramidal dystrophy, non-symptomatic recessive rod-pyramidal dystrophy, recessive Newfoundland rod-pyramidal dystrophy, recessive progressive pyramidal dystrophy,Stickler syndrome, dominant Stickler syndrome, recessive Stickler syndrome, dominant Stickler syndrome type I, dominant Stickler syndrome type II, Marshall syndrome, dominant Marshall syndrome, recessive Marshall syndrome, achromatopsia, recessive monochromatopsia, dominant monochromatopsia, recessive complete monochromatopsia, recessive incomplete monochromatopsia, macular degeneration, age-related macular degeneration, complex etiology age-related macular degeneration, isolated age-related macular degeneration, wet age-related macular degeneration, dry age-related macular degeneration, drusen, recessive drusen, dominant drusen, early-onset recessive drusen Drusen, early-onset dominant drusen, macular drusen, dominant radial macular drusen, pigmentary paravenous retinal choroidal atrophy, recessive pigmentary paravenous retinal choroidal atrophy, dominant pigmentary paravenous retinal choroidal atrophy, progressive bifocal retinal choroidal atrophy, Valday-Beedl syndrome, recessive Valday-Beedl syndrome, dominant Valday-Beedl syndrome, recessive Valday-Beedl syndrome with developmental abnormalities, retinal degeneration, recessive retinal degeneration, dominant retinal degeneration, non-symptomatic recessive retinal degeneration, Doyne honeycomb retinal degeneration, Doyne recessive honeycomb retinal degeneration, Doyne dominant honeycomb retinal degeneration (dominant Doyne honeycomb retinal degeneration) (Malattia reventinese) Leventinese), recessive nephronoplasia with retinal degeneration, Alström syndrome, recessive Alström syndrome, dominant Alström syndrome, Joubert syndrome, recessive Joubert syndrome, dominant Joubert syndrome, Joubert syndrome, recessive Joubert syndrome, dominant Joubert syndrome, X-linked Joubert syndrome, vitreoretinal degeneration, recessive vitreoretinal degeneration, dominant vitreoretinal degeneration, snowflake vitreoretinal degeneration, snowflake dominant vitreoretinal degeneration, Oguchi disease, recessive Oguchi disease, dominant Oguchi disease, night blindness, stasis night blindness, congenital Night blindness, congenital stop night blindness, severe congenital stop night blindness, recessive congenital stop night blindness, recessive complete congenital stop night blindness, dominant congenital stop night blindness, Nougarette type dominant congenital stop night blindness, small-mouth type recessive congenital stop night blindness, Riggs type recessive congenital stop night blindness, Schubert-Bo Runschein type recessive congenital arresting night blindness, white-punctate fundus recessive congenital arresting night blindness, complete recessive congenital arresting night blindness, X-linked congenital arresting night blindness, incomplete X-linked congenital arresting night blindness, retinal vasculopathy, cerebral leukodystrophy, retinal vasculopathy with cerebral leukodystrophy,Recessive retinal vascular disease with cerebral white matter dystrophy, dominant retinal vascular disease with cerebral white matter dystrophy, Eicardi-Gutierre syndrome, Eicardi-Gutierre syndrome 1, recessive Eicardi-Gutierre syndrome 1, dominant Eicardi-Utierre syndrome 1, lupus frostbite, recessive lupus frostbite, dominant lupus frostbite, Martinique retinal dystrophy and retinitis pigmentosa, recessive Martinique retinal dystrophy and retinitis pigmentosa, dominant Martinique retinal dystrophy and retinitis pigmentosa, spinocerebellar ataxia, recessive spinocerebellar ataxia, dominant spinocerebellar ataxia, spinocerebellar ataxia with macular dystrophy, retinal degeneration, Spinocerebellar ataxia with macular dystrophy or retinal degeneration, recessive spinocerebellar ataxia with macular dystrophy or retinal degeneration, dominant spinocerebellar ataxia with macular dystrophy or retinal degeneration, Wolfram syndrome, recessive Wolfram syndrome, dominant Wolfram syndrome, low-frequency sensorineural hearing loss, recessive low-frequency sensorineural hearing loss, dominant low-frequency sensorineural hearing loss, ophthalmo-otitis syndrome, recessive ophthalmo-otitis syndrome, dominant ophthalmo-otitis syndrome, recessive kidney, skeletal and retinal abnormalities, recessive abetalipoproteinemia, microcephaly, recessive microcephaly, dominant microcephaly, growth disorders and retinopathy, recessive microcephaly, Vietti crystal horn Membrane-retinal dystrophy, recessive Vietti crystalline corneal-retinal dystrophy, dominant Vietti crystalline corneal-retinal dystrophy, Wagner's disease, erosive vitreoretinopathy, Wagner's disease and erosive vitreoretinopathy, recessive Wagner's disease and erosive vitreoretinopathy, dominant Wagner's disease and erosive vitreoretinopathy, febrile seizures, recessive febrile seizures, dominant febrile seizures, dominant / recessive febrile seizures, choroidal dystrophy, recessive choroidal dystrophy, dominant choroidal dystrophy, centrally ring-shaped choroidal dystrophy, dominant centrally ring-shaped choroidal dystrophy, recessive centrally ring-shaped choroidal dystrophy Trophy, epiphyseal dysplasia, recessive epiphyseal dysplasia, dominant epiphyseal dysplasia, multiple epiphyseal dysplasia, recessive multiple epiphyseal dysplasia, dominant multiple epiphyseal dysplasia, ichthyosis, recessive ichthyosis, dominant ichthyosis, quadriplegia and delayed recessive ichthyosis, chorioretinal atrophy, bifocal chorioretinal atrophy, progressive bifocal chorioretinal atrophy, recessive progressive bifocal chorioretinal atrophy, dominant progressive bifocal chorioretinal atrophy, Refsum disease, recessive Refsum disease, dominant Refsum disease, adult-type recessive Refsum disease, infant-type recessive Refsum disease, retinal cone dystrophy, recessive retinal cone dystrophy, dominant retinal cone dystrophy, retinal cone dystrophy Fee 1, recessive retinal cone dystrophy 1, dominant retinal cone dystrophy 1, type 3 dichromacy, recessive type 3 dichromacy, dominant type 3 dichromacy, mucopolysaccharidosis, recessive mucopolysaccharidosis, dominant mucopolysaccharidosis, monochromacy Pingelap, recessive monochromacy Pingelap, dominant monochromacy Pingelap, Klippel-Veil syndrome, recessive Klippel-Veil syndrome, dominant Klippel-Veil syndrome, microphthalmia, recessive microphthalmia, dominant microphthalmia, limb-girdle muscular dystrophy, recessive limb-girdle muscular dystrophy, dominant limb-girdle muscular dystrophy, short-rib thoracic dysplasia, recessive short-rib thoracic dysplasia, dominant short-rib thoracic dysplasia,Polydactyly recessive short-rib thoracic dysplasia, retinal dysplasia recessive short-rib thoracic dysplasia, intellectual disability, trunk obesity, retinal dysplasia, and micropenis (MORM) syndrome, recessive MORM syndrome, dominant MORM syndrome, spasticity and retinal degeneration recessive retardation, Cockayne syndrome, recessive Cockayne syndrome, dominant Cockayne syndrome, congenital retinal detachment (nonattachment), recessive nonsyndromic congenital retinal detachment, dominant nonsyndromic congenital retinal detachment, hemolytic anemia, nonspherocytic hemolytic anemia, recessive nonspherocytic hemolytic anemia, dominant nonspherocytic hemolytic anemia, hereditary neuropathy, hereditary neuropathy (Russe type), recessive hereditary neuropathy (Russe type), dominant hereditary neuropathy (Russe type), choroidal sclerosis, recessive choroidal sclerosis, dominant choroidal sclerosis, retinopathy, recessive retinopathy, dominant retinopathy, complex Dominant and recessive retinopathy, diffuse dominant retinopathy, variable dominant retinopathy, diffuse and variable dominant retinopathy, microcephaly, recessive microcephaly, dominant microcephaly, lymphedema-dominant microcephaly, chorioretinopathy-dominant microcephaly, lymphedema- and chorioretinopathy-dominant microcephaly, chorioretinopathy, recessive chorioretinopathy, dominant chorioretinopathy, chorioretinopathy and microcephaly, recessive chorioretinopathy and microcephaly, dominant chorioretinopathy and microcephaly, renal coloboma syndrome, recessive renal coloboma syndrome, dominant renal coloboma syndrome , non-symptomatic hearing loss, recessive non-symptomatic hearing loss, dominant non-symptomatic hearing loss, gyroscopic atrophy, recessive gyroscopic atrophy, dominant gyroscopic atrophy, gyroscopic retinal and choroidal atrophy, vitreoretinopathy, exudative vitreoretinopathy, familial exudative vitreoretinopathy, recessive familial exudative vitreoretinopathy, dominant familial exudative vitreoretinopathy, dominant familial exudative vitreoretinopathy and Coats disease, neovascular inflammatory vitreoretinopathy, recessive neovascular inflammatory vitreoretinopathy, dominant neovascular inflammatory vitreoretinopathy, focal atrophy, recessive focal atrophy, dominant focal atrophy Sexual atrophy, Meckel syndrome, recessive Meckel syndrome, dominant Meckel syndrome, vitreous-retinal choriopathy, recessive vitreous-retinal choriopathy, dominant vitreous-retinal choriopathy, bestrofin syndrome, recessive bestrofin syndrome, dominant bestrofin syndrome, high bone mass trait, recessive high bone mass trait, dominant high bone mass trait, osteoporosis-pseudoglioma syndrome, recessive osteoporosis-pseudoglioma syndrome, dominant osteoporosis-pseudoglioma syndrome, microphthalmia, recessive microphthalmia, dominant microphthalmia, retinal disease syndrome, recessive retinal disease syndrome, dominant retinal disease syndrome,Microphthalmia and retinal disease syndrome, recessive microphthalmia and retinal disease syndrome, dominant microphthalmia and retinal disease syndrome, true microphthalmia, recessive true microphthalmia, dominant true microphthalmia, osteogenesis imperfecta, recessive osteogenesis imperfecta, dominant osteogenesis imperfecta, developmental disorders, osteoarthritis and symptomatic disorders, caudal optic disc malformation, recessive caudal optic disc malformation, dominant caudal optic disc malformation, white punctate fundus, recessive white punctate fundus, dominant white punctate fundus, mevalonic aciduria, recessive mevalonic aciduria, dominant mevalonic aciduria, hyper-IgD syndrome, recessive hyper-IgD Syndrome, dominant hyper-IgD syndrome, spastic paraplegia, recessive spastic paraplegia, dominant spastic paraplegia, neuropathy recessive spastic paraplegia, optic nerve atrophy recessive spastic paraplegia, neuropathy and optic nerve atrophy recessive spastic paraplegia (dementia), recessive dementia, dominant dementia, familial dominant dementia, retinoblastoma, recessive retinoblastoma, dominant retinoblastoma, germline retinoblastoma, somatic retinoblastoma, dominant germline or somatic retinoblastoma, retinoblastoma, benign retinoblastoma, pineal gland tumor, osteosarcoma, rod monochromatic vision (rod Monochromacy), recessive rod monochromacy, dominant rod monochromacy, monochromacy, recessive monochromacy, dominant monochromacy, rod monochromacy, rod recessive monochromacy, rod dominant monochromacy, recessive rod monochromacy or monochromacy, pattern dystrophy, recessive pattern dystrophy, dominant pattern dystrophy, S cone syndrome, reinforced S cone syndrome (ESC), recessive ESC, dominant ESC, Goldmann-Fabre syndrome, recessive Goldmann-Fabre syndrome, dominant Goldmann-Fabre syndrome, Bosniadystrophy, recessive Bosniadystrophy, dominant Bosniadystrophy, white punctate retinitis, recessive white punctate retinitis, dominant white punctate retinitis, mucolipidosis IIIγ , recessive mucolipidosis IIIγ, dominant mucolipidosis IIIγ, Meinzer-Sardino syndrome, recessive Meinzer-Sardino syndrome, dominant Meinzer-Sardino syndrome, pseudoxanthoma elasticum, recessive pseudoxanthoma elasticum, dominant pseudoxanthoma elasticum, Knobloch syndrome, recessive Knobloch syndrome, dominant Knobloch syndrome, foveal hypoplasia, recessive foveal hypoplasia, dominant foveal hypoplasia, anterior segment malformation, recessive anterior segment malformation, dominant anterior segment malformation, foveal hypoplasia and anterior segment malformation, recessive foveal hypoplasia and anterior segment malformation, dominant foveal hypoplasia and anterior segment malformation, spastic ataxia, recessive spastic ataxia, dominant spastic ataxia,De Grouchy syndrome, Boucher-Neuhauser syndrome, recessive Boucher-Neuhauser syndrome, dominant Boucher-Neuhauser syndrome, Boucher-Neuhauser syndrome with chorioretinal dystrophy, recessive Boucher-Neuhauser syndrome with chorioretinal dystrophy, dominant Boucher-Neuhauser syndrome with chorioretinal dystrophy, hypoprebetalipoproteinemia, acanthocyanosis, retinitis pigmentosa, and globus pallidus (HARP) degeneration, recessive HARP degeneration, dominant HARP degeneration, Haller-Forden-Spatz syndrome, recessive Haller-Forden-Spatz syndrome Syndrome, Haller-Forden-Spatz syndrome dominant, Alagille syndrome, recessive Alagille syndrome, dominant Alagille syndrome, polyneuropathy, hearing loss, ataxia, retinitis pigmentosa and early-onset cataract (PHARC), recessive PHARC, dominant PHARC, recessive symptomatic PHARC, Sausby's retinal degeneration, recessive Sausby's retinal degeneration, dominant Sausby's retinal degeneration, vitreoretinal dystrophy, recessive vitreoretinal dystrophy, dominant vitreoretinal dystrophy, optic neuropathy, recessive optic neuropathy, dominant optic neuropathy, late-onset dominant optic neuropathy, mouth-face-finger syndrome 1, Simpson's syndrome Goravi-Boehmer syndrome 2, X-linked retinoschisis, X-linked Oregon eye disease, X-linked optic atrophy, retinal dysplasia, recessive retinal dysplasia, dominant retinal dysplasia, X-linked retinal dysplasia, primary X-linked retinal dysplasia, X-linked Norie disease, Coats disease, X-linked Orlando Island eye disease, autoimmune inner ear disease (AIED), AIED-like disease, colloideremia, X-linked colloideremia, neuropathy, optic atrophy, hearing loss and retinitis pigmentosa, X-linked neuropathy, optic atrophy, hearing loss and retinitis pigmentosa, X-linked blue cone monochromatic vision, X-linked blue cone monochromatic vision (BCM) Type 1 trichromacy and rare macular dystrophy, X-linked type 2 trichromacy and rare macular dystrophy in blue cone monochromacy (BCM), mitochondrial Kearns-Sayer syndrome including retinitis pigmentosa, Leigh syndrome, retinopathy, mitochondrial pigmentary retinopathy and sensorineural hearing loss, albinism, oculocutaneous albinism, neuronal ceroid lipofuscinosis, Zellweger spectrum disorder, cobalamin C deficiency, blue cone monochromacy, hereditary red-green color blindness, type 3 color blindness and yellow-blue abnormalities, latitudinal vision, delayed cone adaptation, uveitis, diabetic retinopathy, diabetic macular edema, persistent corneal epithelial defects,Neurotrophic keratitis, herpes interstitial keratitis, chronic dry eye, glaucoma, ocular detachment, ocular blister formation, ocular scarring, visual loss, blindness, corneal blindness, dry eye disease, tear-deficient dry eye disease, Sjögren's syndrome-related tear-deficient dry eye disease, non-Sjögren's syndrome-related dry eye disease, evaporative dry eye disease, meibomian gland dysfunction, blepharitis, blepharitis, ocular rosacea and atopic dermatitis, tear-deficient and evaporative dry eye diseases, Fuchs dystrophy, Fuchs corneal endothelial dystrophy (FE) CD), Fuchs' endothelial dystrophy (FED), panuveitis, diffuse uveitis, panuveitis, cataract, partial cataract, complete cataract, absent cataract, progressive cataract, hard cataract, soft cataract, nuclear cataract, nuclear sclerosis cataract, cortical cataract, posterior subcapsular cataract, congenital cataract, corneal dystrophy, epithelial and subepithelial dystrophy, epithelial basement membrane dystrophy, epithelial recurrent erosive dystrophy (Franschetti corneal dystrophy, Dystrophia smolandiensis (Dystrophia) Smolandiensis, and / or Dystrophia Helsinglandica, subepithelial mucinous corneal dystrophy, Miesmann corneal dystrophy, Risch epithelial corneal dystrophy, gelatinous drop-like corneal dystrophy, Bowman layer dystrophy, Reiss-Bücklers corneal dystrophy, Thiel-Benkhe corneal dystrophy, stromal dystrophy-TGFB1 corneal dystrophy, lattice corneal dystrophy, type 1 variant of lattice corneal dystrophy (III, IIIA, I / IIIA, IV), granular corneal dystrophy type 1, granular corneal dystrophy type 2, stromal dystrophy, maculoplasty, Schneider crystalline corneal dystrophy, congenital stromal corneal dystrophy, Fleck's membrane dystrophy, posterior amorphous corneal dystrophy, François central cloud dystrophy. Cloudy dystrophy of Francois, predescemet's corneal dystrophy, endothelial dystrophy, Fuchs' dystrophy, posterior polymorphic corneal dystrophy, congenital hereditary endothelial dystrophy, X-linked corneal endothelial dystrophy, superficial dystrophy, epithelial basement membrane dystrophy,The following are selected from the group consisting of Miesmann's juvenile corneal epithelial dystrophy, gelatinous drop-like corneal dystrophy, Risch's epithelial corneal dystrophy, subepithelial mucinous corneal dystrophy, Reiss-Bücklers corneal dystrophy, Thiel-Benkhe dystrophy, stromal dystrophy, lattice corneal dystrophy, granular corneal dystrophy, maculoplasty, Schneider crystalline corneal dystrophy, congenital stromal corneal dystrophy, Fleck's dystrophy, posterior dystrophy, Fuchs' dystrophy, posterior polymorphic corneal dystrophy, congenital hereditary endothelial dystrophy, keratopathy, keratopathy, corneal keratopathy, and calcific keratopathy. In some embodiments, The eye condition or disease is Stargardt syndrome. In some embodiments, the eye condition or disease is neurotrophic keratitis. In some embodiments, the eye condition or disease is Leber's congenital amaurosis. In some embodiments that may be combined with any of the above embodiments, the subject is a human. In some embodiments that may be combined with any of the above embodiments, the herpesvirus or pharmaceutical composition is administered to the subject by injection, by injection into the eye, by subretinal injection, by intraocular injection, by intravitreous injection, by suprachoroidal injection, intraocular, intravitreous, topically, subcutaneously, subconjunctivally, subtenon, intraanterior chamber, retroocular, systemically, parenterally, periocularly, near the sclera, near the anterior sclera, near the posterior sclera, orally, periocularly, or suprachoroidally.

[0020] Other aspects of this disclosure relate to any of the recombinant herpesviruses and / or pharmaceutical compositions described herein for use in treating eye conditions or diseases in subjects where such treatment is necessary.

[0021] Another aspect of this disclosure relates to a method for treating an eye condition or disease in a subject in need, comprising administering to the subject an effective amount of any of the recombinant herpesviruses and / or pharmaceutical compositions described herein.

[0022] In any of the above embodiments, the eye condition or disease is retinitis pigmentosa, recessive retinitis pigmentosa, severe recessive retinitis pigmentosa, dominant retinitis pigmentosa, dominant retinitis pigmentosa with choroidal lesions, recessive retinitis pigmentosa with parapetiolar preservation of RPE (PPRPE), recessive retinitis pigmentosa with posterior column ataxia (PCARP), recessive retinitis pigmentosa with microcytosis, symptomatic recessive retinitis pigmentosa, recessive symptomatic disease with retinitis pigmentosa, non-symptomatic recessive retinitis pigmentosa, non-symptomatic dominant retinitis pigmentosa, symptomatic dominant retinitis pigmentosa, juvenile recessive retinitis pigmentosa, recessive retinitis pigmentosa, and intellectual disability, macular degeneration. Recessive retinitis pigmentosa with associated conditions, severe early-onset recessive retinitis pigmentosa, recessive retinitis pigmentosa with bone malformations, recessive retinitis pigmentosa with skeletal abnormalities, dominant retinitis pigmentosa with sensorineural hearing loss, recessive retinitis pigmentosa with hearing loss, recessive retinitis pigmentosa with hearing loss and additional disability, recessive retinitis pigmentosa with vitreous degeneration, early-onset recessive retinitis pigmentosa with macular defect, X-linked retinitis pigmentosa, recessive X-linked retinitis pigmentosa, dominant X-linked retinitis pigmentosa, severe X-linked retinitis pigmentosa, X-linked retinitis pigmentosa with intellectual disability, X-linked retinitis pigmentosa with myopathy, Valdey-Beedle-like network Membrane pigmentosa, Balday-Beedl-like recessive retinitis pigmentosa, bigenic retinitis pigmentosa, bigenic retinitis pigmentosa with retinal outer segment membrane protein 1, bigenic retinitis pigmentosa with PRPH2, recessive retinitis pigmentosa with early macular lesions, recessive hearing loss without retinitis pigmentosa, recessive congenital hearing loss without retinitis pigmentosa, recessive retinitis pigmentosa and recessive ataxia, recessive retinitis pigmentosa and dominant ataxia, mitochondrial retinitis pigmentosa, mitochondrial retinitis pigmentosa with developmental and neurological abnormalities, mitochondrial retinitis pigmentosa with progressive sensorineural hearing loss, hearing loss and neurological abnormalities Mitochondrial retinitis pigmentosa, autosomal dominant retinitis pigmentosa, asymptomatic autosomal dominant retinitis pigmentosa, autosomal recessive retinitis pigmentosa, asymptomatic autosomal recessive retinitis pigmentosa, retinal pigment epithelium (RPE), recessive RPE, dominant RPE, recessive RPE degeneration, dominant RPE degeneration, ataxia, recessive ataxia, dominant ataxia, Senior-Loken syndrome, recessive Senior-Loken syndrome, dominant Senior-Loken syndrome, nephronoplasia, recessive nephronoplasia, dominant nephronoplasia, adolescent recessive nephronoplasia, ciliopathy-associated recessive nephronoplasia, juvenile nephronoplasia, juvenile recessive nephronoplasia, juvenile dominant nephronoplasia,Usher syndrome, Usher syndrome type I, Usher syndrome type II, Usher syndrome type III, recessive Usher syndrome, atypical recessive Usher syndrome, dominant Usher syndrome, type 2 recessive Usher syndrome, type 2a recessive Usher syndrome, type 3 recessive Usher syndrome, type 3-like recessive Usher syndrome, atypical recessive Usher syndrome, type 1 recessive Usher syndrome, type 1b recessive Usher syndrome, type 1d recessive Usher syndrome, type 1f recessive Usher syndrome, type 1J recessive Usher syndrome, type 1k recessive Usher syndrome, bigenic Usher syndrome with CDH23 Usher syndrome, bigenic Usher syndrome with PCDH15, Acadian recessive Usher syndrome, recessive atypical Usher syndrome (USH3-like), Leber congenital amaurosis, recessive Leber congenital amaurosis, dominant Leber congenital amaurosis, de novo Leber congenital amaurosis, dominant Leber congenital amaurosis and pituitary dysfunction, recessive Leber congenital amaurosis with myopathy, recessive Leber congenital amaurosis with severe childhood retinal dystrophy, mitochondrial Leber hereditary optic neuropathy, Leber hereditary optic neuropathy, optic nerve atrophy, recessive optic nerve atrophy, dominant optic nerve atrophy, Optic atrophy with ataxia, recessive optic atrophy with ataxia, dominant optic atrophy with ataxia, recessive optic atrophy with ataxia and 3-methylglutaconic aciduria, cataract, dominant optic atrophy with ataxia and anreflexia, Kaer-type dominant optic atrophy, dominant optic atrophy with sensorineural hearing loss, recessive cerebellar degeneration with optic atrophy, optic atrophy with anesthesia-dystonia syndrome, X-linked optic atrophy with anesthesia-dystonia syndrome, retinal dystrophy, recessive retinal dystrophy, dominant retinal dystrophy, hereditary retinal dystrophy, early-onset recessive retinal dystrophy, Recessive symptomatic retinal dystrophy, recessive asymptomatic retinal dystrophy, recessive symptomatic and asymptomatic retinal dystrophy, recessive optic atrophy and retinal dystrophy, recessive retinal dystrophy and obesity, recessive retinal dystrophy and cerebellar dysplasia, symptomatic recessive optic atrophy and retinal dystrophy, dominant retinal dystrophy with iris defects, ciliopathy spectrum including retinal dystrophy, recessive ciliopathy spectrum including retinal dystrophy, dominant ciliopathy spectrum including retinal dystrophy, dominant optic atrophy with neuropathy and myopathy,Dominant optic atrophy with intellectual disability and developmental delay, symptomatic optic atrophy, asymptomatic optic atrophy, recessive asymptomatic optic atrophy, dominant asymptomatic optic atrophy, recessive symptomatic optic atrophy, dominant symptomatic optic atrophy, Charcot-Marie-Tooth disease, recessive Charcot-Marie-Tooth disease, dominant Charcot-Marie-Tooth disease, benign spotted retina, recessive benign spotted retina, dominant benign spotted retina, symptomatic retinopathy, recessive symptomatic retinopathy, dominant symptomatic retinopathy, Batten disease, recessive Batten disease, dominant Batten disease, recessive Batten disease (neuroceroid lipofuscinosis type 3), juvenile recessive Batten disease (neuroceroid lipofuscinosis type 3) Ceroid lipofuscinosis type 3), neuronal ceroid lipofuscinosis, recessive neuronal ceroid lipofuscinosis, recessive neuronal ceroid lipofuscinosis type 1, dominant neuronal ceroid lipofuscinosis, Stargart disease, recessive Stargart disease, dominant Stargart disease, juvenile Stargart disease, late-onset Stargart disease, Stargart-like macular dystrophy, recessive Stargart-like macular dystrophy, dominant Stargart-like macular dystrophy, macular dystrophy, recessive macular dystrophy, early-onset macular dystrophy, adult-onset macular dystrophy, early-onset recessive macular dystrophy Stroke, adult-onset recessive macular dystrophy, early adult-onset recessive macular dystrophy, juvenile recessive macular dystrophy with hypotrichosis, dominant macular dystrophy, late-onset dominant macular dystrophy, dominant macular dystrophy with lens zonules, bullseye dominant macular dystrophy, butterfly-shaped dominant macular dystrophy, age-related dominant macular dystrophy, benign concentric annular dominant macular dystrophy, vitelloid recessive macular dystrophy, vitelloid dominant macular dystrophy, atypical vitelloid dominant macular dystrophy, dominant adult-type vitelloid macular dystrophy, Stargard-like dominant Macular dystrophy, Stargard-type dominant macular dystrophy, North Carolina-type dominant macular dystrophy, North Carolina-like dominant macular dystrophy, North Carolina-like dominant macular dystrophy with progressive sensorineural hearing loss, cystoid dominant macular dystrophy, Best-type dominant macular dystrophy, occult macular dystrophy, recessive occult macular dystrophy, dominant occult macular dystrophy, age-related familial macular dystrophy, X-linked atrophic macular dystrophy, recessive X-linked atrophic macular dystrophy, dominant X-linked atrophic macular dystrophy,Mitochondrial macular pattern dystrophy with type II diabetes and hearing loss, macular dystrophy, recessive macular dystrophy, dominant macular dystrophy, rod dystrophy, recessive rod dystrophy, dominant rod dystrophy, cone dystrophy, recessive cone dystrophy, dominant cone dystrophy, recessive cone dystrophy with supernormal rod electroretinogram, early-onset recessive cone dystrophy, late-onset recessive cone dystrophy, cone dystrophy 1, X-linked cone dystrophy 1, cone dystrophy 2, progressive cone dystrophy 2, X-linked progressive cone dystrophy 2 Delayed cone adaptation, recessive delayed cone adaptation, dominant delayed cone adaptation, cone-rod dystrophy, recessive cone-rod dystrophy, dominant cone-rod dystrophy, isolated cone-rod dystrophy, progressive cone-rod dystrophy, X-linked cone-rod dystrophy, X-linked progressive cone-rod dystrophy, progressive dominant cone-rod dystrophy, cone-rod dystrophy and enamel hypoplasia syndrome, recessive cone-rod dystrophy and enamel hypoplasia syndrome, dominant cone-rod dystrophy and enamel hypoplasia syndrome, recessive cone-rod with internal retinopathy Rod-rod dystrophy, recessive pyramidal-rod dystrophy with bone disease, congenital symptomatic non-progressive recessive pyramidal-rod dystrophy, recessive pyramidal-rod dystrophy with hearing loss, recessive pyramidal-rod dystrophy with psychomotor retardation, recessive pyramidal and pyramidal-rod dystrophy, pyramidal-rod synaptic disease, congenital pyramidal-rod synaptic disease, recessive congenital pyramidal-rod synaptic disease, dominant congenital pyramidal-rod synaptic disease, rod-pyramidal dystrophy, recessive rod-pyramidal dystrophy, dominant rod-pyramidal dystrophy, early-onset recessive rod-pyramidal dystrophy, non-symptomatic recessive rod-pyramidal dystrophy, recessive neodystrophy Fundland rod-cone dystrophy, recessive progressive cone dystrophy, Stickler syndrome, dominant Stickler syndrome, recessive Stickler syndrome, dominant Stickler syndrome type I, dominant Stickler syndrome type II, Marshall syndrome, dominant Marshall syndrome, recessive Marshall syndrome, monochromacy, recessive monochromacy, dominant monochromacy, recessive complete monochromacy, recessive incomplete monochromacy, macular degeneration, age-related macular degeneration, complex etiology age-related macular degeneration, isolated age-related macular degeneration, wet age-related macular degeneration, dry age-related macular degeneration, drusen, recessive drusen, dominant drusen,Early-onset recessive drusen, early-onset dominant drusen, macular drusen, dominant radial macular drusen, pigmentary paravenous retinal choroidal atrophy, recessive pigmentary paravenous retinal choroidal atrophy, dominant pigmentary paravenous retinal choroidal atrophy, progressive bifocal retinal choroidal atrophy, Valday-Beedl syndrome, recessive Valday-Beedl syndrome, dominant Valday-Beedl syndrome, recessive Valday-Beedl syndrome with developmental abnormalities, retinal degeneration, recessive retinal degeneration, dominant retinal degeneration, non-symptomatic recessive retinal degeneration, Doynn's honeycomb retinal degeneration, Doynn's recessive honeycomb retinal degeneration, Doynn's dominant honeycomb retinal degeneration (Malattiya) Reventinese, recessive nephronoplasia with retinal degeneration, Alström syndrome, recessive Alström syndrome, dominant Alström syndrome, Joubert syndrome, recessive Joubert syndrome, dominant Joubert syndrome, Joubert syndrome, recessive Joubert syndrome, dominant Joubert syndrome, X-linked Joubert syndrome, vitreoretinal degeneration, recessive vitreoretinal degeneration, dominant vitreoretinal degeneration, snowflake vitreoretinal degeneration, snowflake Rake-dominant vitreoretinal degeneration, small mouth disease, recessive small mouth disease, dominant small mouth disease, night blindness, stop night blindness, congenital night blindness, congenital stop night blindness, severe congenital stop night blindness, recessive congenital stop night blindness, recessive complete congenital stop night blindness, dominant Congenital arresting night blindness, Nougarette type dominant congenital arresting night blindness, small-mouth type recessive congenital stopping night blindness, Riggs type recessive congenital stopping night blindness, Schubert-Bornschein type recessive congenital stopping night blindness, white-punctate fundus type recessive congenital stopping night blindness Retinal night blindness, complete recessive congenital stasis, X-linked congenital stasis, incomplete X-linked congenital stasis, retinal vascular disease, cerebral leukodystrophy, retinal vascular disease with cerebral leukodystrophy, recessive retinal vascular disease with cerebral leukodystrophy, dominant retinal vascular disease with cerebral leukodystrophy, Eicardi-Gutierre syndrome, Eicardi-Gutierre syndrome 1, recessive Eicardi-Gutierre syndrome 1, dominant Aicardi-Uthier syndrome 1, lupus frostbite, recessive lupus frostbite, dominant lupus frostbite, Martinique retinal dystrophy and retinitis pigmentosa, recessive Martinique retinal dystrophy and retinitis pigmentosa, dominant Martinique retinal dystrophy and retinitis pigmentosa, spinocerebellar ataxia, recessive spinocerebellar ataxia, dominant spinocerebellar ataxia, spinocerebellar ataxia with macular dystrophy, spinocerebellar ataxia with retinal degeneration,Spinocerebellar ataxia with macular dystrophy or retinal degeneration, recessive spinocerebellar ataxia with macular dystrophy or retinal degeneration, dominant spinocerebellar ataxia with macular dystrophy or retinal degeneration, Wolfram syndrome, recessive Wolfram syndrome, dominant Wolfram syndrome, low-frequency sensorineural hearing loss, recessive low-frequency sensorineural hearing loss, dominant low-frequency sensorineural hearing loss, ophthalmo-otitis syndrome, recessive ophthalmo-otitis syndrome, dominant ophthalmo-otitis syndrome, recessive kidney, skeletal and retinal abnormalities, recessive abetalipoproteinemia, microcephaly, recessive microcephaly, dominant microcephaly, Growth disorders and retinopathy, recessive microcephaly, Vietti crystalline corneal-retinal dystrophy, recessive Vietti crystalline corneal-retinal dystrophy, dominant Vietti crystalline corneal-retinal dystrophy, Wagner disease, erosive vitreoretinopathy, Wagner disease and erosive vitreoretinopathy, recessive Wagner disease and erosive vitreoretinopathy, dominant Wagner disease and erosive vitreoretinopathy, febrile seizures, recessive febrile seizures, dominant febrile seizures, dominant / recessive febrile seizures, choroidal dystrophy, recessive choroidal dystrophy, dominant choroidal dystrophy, centrally ring-shaped choroidal dystrophy, dominant centrally ring-shaped Choroidal dystrophy, recessive central ring-spot choroidal dystrophy, epiphyseal dysplasia, recessive epiphyseal dysplasia, dominant epiphyseal dysplasia, multiple epiphyseal dysplasia, recessive multiple epiphyseal dysplasia, dominant multiple epiphyseal dysplasia, ichthyosis, recessive ichthyosis, dominant ichthyosis, quadriplegic and delayed recessive ichthyosis, chorioretinal atrophy, bifocal chorioretinal atrophy, progressive bifocal chorioretinal atrophy, recessive progressive bifocal chorioretinal atrophy, dominant progressive bifocal chorioretinal atrophy, Refsum disease, recessive Refsum disease, dominant Refsum disease, adult-onset recessive Refsum disease, infantile recessive Refsum disease, retinal cone dystrophy, recessive retinal cone dystrophy, Dominant retinal cone dystrophy, retinal cone dystrophy 1, recessive retinal cone dystrophy 1, dominant retinal cone dystrophy 1, type 3 dichromacy, recessive type 3 dichromacy, dominant type 3 dichromacy, mucopolysaccharidosis, recessive mucopolysaccharidosis, dominant mucopolysaccharidosis, monochromacy Pingelap, recessive monochromacy Pingelap, dominant monochromacy Pingelap, Klippel-Veil syndrome, recessive Klippel-Veil syndrome, dominant Klippel-Veil syndrome, microphthalmia, recessive microphthalmia, dominant microphthalmia, limb-girdle muscular dystrophy, recessive limb-girdle muscular dystrophy, dominant limb-girdle muscular dystrophy, short-rib thoracic dysplasia, recessive short-rib Costochondral dysplasia, dominant short-costochondral dysplasia, polydactyly recessive short-costochondral dysplasia, retinal dystrophy recessive short-costochondral dysplasia, intellectual disability, trunk obesity, retinal dysplasia, and micropenis (MORM) syndrome, recessive MORM syndrome, dominant MORM syndrome, spasticity and retinal degeneration recessive intellectual disability, Cockayne syndrome, recessive Cockayne syndrome, dominant Cockayne syndrome, congenital retinal detachment, recessive non-syndromic congenital retinal detachment, dominant non-syndromic congenital retinal detachment, hemolytic anemia, nonspherocytic hemolytic anemia, recessive nonspherocytic hemolytic anemia, dominant nonspherocytic hemolytic anemia, hereditary neuropathy,Hereditary neuropathy (Lasse type), recessive hereditary neuropathy (Lasse type), dominant hereditary neuropathy (Lasse type), choroidal sclerosis, recessive choroidal sclerosis, dominant choroidal sclerosis, retinopathy, recessive retinopathy, dominant retinopathy, combined dominant and recessive retinopathy, diffuse dominant retinopathy, variable dominant retinopathy, diffuse and variable dominant retinopathy, microcephaly, recessive microcephaly, dominant microcephaly, lymphedema-dominant microcephaly, chorioretinopathy-dominant microcephaly, lymphedema-dominant and chorioretinopathy-dominant microcephaly, chorioretinopathy, recessive chorioretinopathy, dominant chorioretinopathy, chorioretinopathy and microcephaly, recessive chorioretinopathy and micro Microcephaly, dominant chorioretinopathy and microcephaly, renal coloboma syndrome, recessive renal coloboma syndrome, dominant renal coloboma syndrome, asymptomatic hearing loss, recessive asymptomatic hearing loss, dominant asymptomatic hearing loss, gyrocephalic atrophy, recessive gyrocephalic atrophy, dominant gyrocephalic atrophy, gyrocephalic retinal choroidal atrophy, vitreoretinopathy, exudative vitreoretinopathy, familial exudative vitreoretinopathy, recessive familial exudative vitreoretinopathy, dominant familial exudative vitreoretinopathy, dominant familial exudative vitreoretinopathy and Coats disease, neovascular inflammatory vitreoretinopathy, recessive neovascular inflammatory vitreoretinopathy, dominant neovascular inflammatory vitreoretinopathy, focal atrophy, recessive Sex-limited focal atrophy, dominant focal atrophy, Meckel syndrome, recessive Meckel syndrome, dominant Meckel syndrome, vitreous-retinal choriolopathy, recessive vitreous-retinal choriolopathy, dominant vitreous-retinal choriolopathy, bestrofin syndrome, recessive bestrofin syndrome, dominant bestrofin syndrome, high bone mass trait, recessive high bone mass trait, dominant high bone mass trait, osteoporosis-pseudoglioma syndrome, recessive osteoporosis-pseudoglioma syndrome, dominant osteoporosis-pseudoglioma syndrome, microphthalmia, recessive microphthalmia, dominant microphthalmia, retinal disease syndrome, recessive retinal disease syndrome, dominant retinal disease syndrome, microphthalmia and retinal disease syndrome, recessive microphthalmia and retinal disease Symptom syndrome, dominant microphthalmia and retinal disease syndrome, true microphthalmia, recessive true microphthalmia, dominant true microphthalmia, osteogenesis imperfecta, recessive osteogenesis imperfecta, dominant osteogenesis imperfecta, developmental disorders, osteoarthritis and symptomatic disorders, caudal optic disc malformation, recessive caudal optic disc malformation, dominant caudal optic disc malformation, white punctate fundus, recessive white punctate fundus, dominant white punctate fundus, mevalonic aciduria, recessive mevalonic aciduria, dominant mevalonic aciduria, hyper-IgD syndrome, recessive hyper-IgD syndrome, dominant hyper-IgD syndrome, spastic paraplegia, recessive spastic paraplegia, dominant spastic paraplegia, neuropathy recessive spastic paraplegia, optic nerve atrophy recessive spastic paraplegia,Neuropathy and optic nerve atrophy, recessive spastic paraplegia (dementia), recessive dementia, dominant dementia, familial dominant dementia, retinoblastoma, recessive retinoblastoma, dominant retinoblastoma, germline retinoblastoma, somatic retinoblastoma, dominant germline or somatic retinoblastoma, retinoblastoma, benign retinoblastoma, pineal gland, osteosarcoma, rod monochromacy, recessive rod monochromacy, dominant rod monochromacy, monochromacy, recessive monochromacy, dominant monochromacy, rod monochromacy, rod recessive monochromacy, rod dominant monochromacy, recessive rod monochromacy or monochromacy, pattern dystrophy, recessive pattern dystrophy, dominant pattern dystrophy S cone syndrome, reinforced S cone syndrome (ESC), recessive ESC, dominant ESC, Goldmann-Fabre syndrome, recessive Goldmann-Fabre syndrome, dominant Goldmann-Fabre syndrome, Bosniadystrophy, recessive Bosniadystrophy, dominant Bosniadystrophy, white punctate retinitis, recessive white punctate retinitis, dominant white punctate retinitis, mucolipidosis IIIγ, recessive mucolipidosis IIIγ, dominant mucolipidosis IIIγ, Mainzer-Sardino syndrome, recessive Mainzer-Sardino syndrome, dominant Mainzer-Sardino syndrome, elastic Fibromic pseudoxanthoma, recessive pseudoxanthoma elastica, dominant pseudoxanthoma elastica, Knobloch syndrome, recessive Knobloch syndrome, dominant Knobloch syndrome, foveal hypoplasia, recessive foveal hypoplasia, dominant foveal hypoplasia, anterior segment malformation, recessive anterior segment malformation, dominant anterior segment malformation, foveal hypoplasia and anterior segment malformation, recessive foveal hypoplasia and anterior segment malformation, dominant foveal hypoplasia and anterior segment malformation, spastic ataxia, recessive spastic ataxia, dominant spastic ataxia, de Grouchy syndrome, Boucher-Neuhauser syndrome, recessive Boucher-Neuhauser syndrome, dominant Boucher-Neuhauser Ihauser syndrome, Boucher-Neuhauser syndrome with chorioretinal dystrophy, recessive Boucher-Neuhauser syndrome with chorioretinal dystrophy, dominant Boucher-Neuhauser syndrome with chorioretinal dystrophy, hypoprebetalipoproteinemia, polyacanthocytosis, retinitis pigmentosa, and globus pallidus (HARP) degeneration, recessive HARP degeneration, dominant HARP degeneration, Haller-Folden-Spatz syndrome, recessive Haller-Folden-Spatz syndrome, dominant Haller-Folden-Spatz syndrome, Alagille syndrome, recessive Alagille syndrome, dominant Alagille syndrome,Multiple neuropathy, hearing loss, ataxia, retinitis pigmentosa and early-onset cataract (PHARC), recessive PHARC, dominant PHARC, recessive symptomatic PHARC, Sausby's retinal degeneration, recessive Sausby's retinal degeneration, dominant Sausby's retinal degeneration, vitreoretinal dystrophy, recessive vitreoretinal dystrophy, dominant vitreoretinal dystrophy, optic neuropathy, recessive optic neuropathy, dominant optic neuropathy, late-onset dominant optic neuropathy, mouth-face-finger syndrome1, Simpson-Goravi-Boehmel syndrome2, X-linked retinoschisis, X-linked Oregon eye disease, X-linked optic atrophy, retinal dysplasia, recessive retinoschisis Membrane dysplasia, dominant retinal dysplasia, X-linked retinal dysplasia, primary X-linked retinal dysplasia, X-linked Norie disease, Coats disease, X-linked Åland Island eye disease, autoimmune inner ear disease (AIED), AIED-like disease, colloideremia, X-linked colloideremia, neuropathy, optic nerve atrophy, hearing loss and retinitis pigmentosa, X-linked neuropathy, optic nerve atrophy, hearing loss and retinitis pigmentosa, X-linked blue cone monochromacy, X-linked type 1 trichromacy and rare macular dystrophy in blue cone monochromacy (BCM), X-linked type 2 trichromacy and rare macular dystrophy Trophy, mitochondrial Kearns-Sayer syndrome including retinitis pigmentosa, Leigh syndrome, retinopathy, mitochondrial pigmentary retinopathy and sensorineural hearing loss, albinism, oculocutaneous albinism, neuronal ceroid lipofuscinosis, Zellweger spectrum disorder, cobalamin C deficiency, blue cone monochromacy, hereditary red-green color blindness, type 3 color blindness and yellow-blue abnormalities, strepoptic vision, delayed cone adaptation, uveitis, diabetic retinopathy, diabetic macular edema, persistent corneal epithelial defect, neurotrophic keratitis, herpes interstitial keratitis, chronic dry eye, glaucoma, ocular detachment, ocular blister formation, ocular scarring, visual impairment, loss of vision. Brightness, corneal blindness, dry eye disease, tear-deficient dry eye disease, Sjögren's syndrome-related tear-deficient dry eye disease, non-Sjögren's syndrome-related dry eye disease, evaporative dry eye disease, meibomian gland dysfunction, blepharitis, blepharitis, ocular rosacea and atopic dermatitis, tear-deficient and evaporative dry eye diseases, Fuchs dystrophy, Fuchs corneal endothelial dystrophy (FECD), Fuchs endothelial dystrophy (FED), panuveitis, diffuse uveitis, panuveitis, cataract, partial cataract, complete cataract, sedentary cataract, progressive cataract, hard cataract,Soft cataracts, nuclear cataracts, nuclear sclerotic cataracts, cortical cataracts, posterior subcapsular cataracts, congenital cataracts, corneal dystrophy, epithelial and subepithelial dystrophy, epithelial basement membrane dystrophy, epithelial recurrent erosive dystrophy (Franschetti corneal dystrophy, Dystrophia smolandiensis, and / or Dystrophia helsinglandica), subepithelial mucinous corneal dystrophy, Miesmann corneal dystrophy, Risch epithelial corneal dystrophy, gelatinous drop-like corneal dystrophy, Boma Layer dystrophy, Reiss-Bücklers corneal dystrophy, Thiel-Benkhe corneal dystrophy, stromal dystrophy-TGFB1 corneal dystrophy, lattice corneal dystrophy, type 1 variant of lattice corneal dystrophy (III, IIIA, I / IIIA, IV), granular corneal dystrophy type 1, granular corneal dystrophy type 2, stromal dystrophy, maculoplasty, Schneider crystalline corneal dystrophy, congenital stromal corneal dystrophy, Fleck's dystrophy Posterior amorphous corneal dystrophy, François central cloud dystrophy, anterior Descemet's membrane corneal dystrophy, endothelial dystrophy, Fuchs dystrophy, posterior polymorphic corneal dystrophy, congenital hereditary endothelial dystrophy, X-linked corneal endothelial dystrophy, superficial dystrophy, epithelial basement membrane dystrophy, Miesmann juvenile corneal epithelial dystrophy, gelatinous drop-like corneal dystrophy, Riesz epithelial corneal dystrophy, subepithelial mucinous corneal dystrophy, Riesz-Bücklers The group can be selected from corneal dystrophy, Thiel-Benkhe dystrophy, stromal dystrophy, lattice corneal dystrophy, granular corneal dystrophy, maculoplasty, Schneider crystalline corneal dystrophy, congenital stromal corneal dystrophy, Fleck's dystrophy, posterior dystrophy, Fuchs dystrophy, posterior polymorphic corneal dystrophy, congenital hereditary endothelial dystrophy, keratopathy, keratopathy, corneal keratopathy, and calcific keratopathy. In some embodiments, the eye condition or disease is Stargardt syndrome. In some embodiments, the eye condition or disease is neurotrophic keratitis. In some embodiments,The eye condition or disease is Leber's congenital monocular cyst. In some embodiments which may be combined with any of the above embodiments, the subject is human. In some embodiments which may be combined with any of the above embodiments, the herpesvirus or pharmaceutical composition is administered to the subject by injection, by injection into the eye, by subretinal injection, by intraocular injection, by intravitreous injection, intraocular, intravitreous, topically, subcutaneously, subconjunctivally, subtenon, intraanterior chamber, retroocular, systemically, parenterally, periophthalmos, near the sclera, near the anterior sclera, near the posterior sclera, orally, periophthalmos, or choroidal. .

[0023] Other aspects of the present disclosure relate to a method for delivering polypeptides to one or more cells in the eye of a subject, comprising administering to the subject a pharmaceutical composition comprising (a) a herpesvirus comprising a recombinant herpesvirus genome, wherein the recombinant herpesvirus genome comprises one or more polynucleotides encoding a polypeptide, and (b) a pharmaceutically acceptable carrier. In some embodiments, the subject suffers from a disease or condition affecting one or more cells in the eye.

[0024] In some embodiments that can be combined with any of the above embodiments, the herpesvirus is a pseudotyped virus. In some embodiments that can be combined with any of the above embodiments, the herpesvirus is not a pseudotyped virus. In some embodiments that can be combined with any of the above embodiments, the herpesvirus is not a pseudotyped oncolytic virus.

[0025] Other aspects of this disclosure relate to a manufactured article or kit comprising any of the recombinant nucleic acids, viruses, pharmaceuticals, and / or pharmaceutical compositions or formulations described herein, and instructions for administration thereof. [Brief explanation of the drawing]

[0026] [Figure 1-1]Figures 1A-1l show schematic diagrams of the wild-type and modified herpes simplex virus genomes. Figure 1A shows the wild-type herpes simplex virus genome. Figure 1B shows the modified herpes simplex virus genome, which includes deletions of the coding sequences for ICP4 (both copies) and incorporates expression cassettes containing nucleic acids encoding polypeptides into each ICP4 locus. [Figure 1-2] Figure 1A-1l shows schematic diagrams of the wild-type and modified herpes simplex virus genomes. Figure 1C shows a modified herpes simplex virus genome with deletions of the coding sequences for ICP4 (both copies) and UL41, and an expression cassette containing nucleic acid encoding a polypeptide incorporated into each of the ICP4 loci. Figure 1D shows a modified herpes simplex virus genome with deletions of the coding sequences for ICP4 (both copies) and UL41, and an expression cassette containing nucleic acid encoding a polypeptide incorporated into the UL41 locus. [Figure 1-3] Figure 1A-1l shows schematic diagrams of wild-type and modified herpes simplex virus genomes. Figure 1E shows a modified herpes simplex virus genome with deletions of the coding sequences for ICP4 (both copies) and ICP22, and an expression cassette containing nucleic acid encoding a polypeptide integrated into each ICP4 locus. Figure 1F shows a modified herpes simplex virus genome with deletions of the coding sequences for ICP4 (both copies) and ICP22, and an expression cassette containing nucleic acid encoding a polypeptide integrated into the ICP22 locus. [Figure 1-4] Figure 1A-1l shows schematic diagrams of wild-type and modified herpes simplex virus genomes. Figure 1G shows a modified herpes simplex virus genome in which an expression cassette containing polypeptide-encoding nucleic acid is incorporated into each of the ICP4 loci, including deletions of the coding sequences for ICP4 (both copies), UL41, and ICP22. Figure 1H shows a modified herpes simplex virus genome in which an expression cassette containing polypeptide-encoding nucleic acid is incorporated into the UL41 locus, including deletions of the coding sequences for ICP4 (both copies), UL41, and ICP22. [Figure 1-5]Figure 1A-1l shows schematic diagrams of the wild-type and modified herpes simplex virus genomes. Figure 1I shows a modified herpes simplex virus genome in which an expression cassette containing nucleic acids encoding a polypeptide is incorporated at the ICP22 locus, including deletions of the coding sequences for ICP4 (both copies), UL41, and ICP22. [Figure 2] This shows the quantification of the vector genome by qPCR in mouse plasma samples collected 24 hours after administration of HSV-mCherry in the anterior chamber, choroid, vitreous, or subretinal regions. Data are presented as mean ± mean standard error (SEM) (n=3 / group). [Figure 3] Figures 3A-3F show histological images obtained by H&E staining (Figure 3A) and in vivo expression of a fluorescent reporter 24 hours after intracavitary administration of HSV-mCherry (Figures 3B-3F). mCherry (red) was co-stained with DAPI (nuclear marker; blue) and / or N-cadherin (corneal endothelial cell marker; green). [Figure 4-1] Figures 4A–4G show in vivo expression of a fluorescent reporter 24 hours after HSV-mCherry administration (Figures 4A–4F) and histological images by H&E staining (Figure 4G). mCherry (red) was co-stained with DAPI (nuclear marker; blue), rhodopsin (RHO; photoreceptor marker; green), and / or isomerohydrolase (isomerophydrolase) / RPE65 (retinal pigment epithelial cell (RPEC) marker; green). [Figure 4-2] See the explanation in Figure 4-1. [Figure 5-1] Figures 5A–5F show in vivo expression of a fluorescent reporter and histological images (Figure 5F) obtained by H&E staining 24 hours after intravitreous administration of HSV-mCherry (Figures 5A–5E). mCherry (red) was co-stained with DAPI (nuclear marker; blue) and / or N-cadherin (corneal endothelial cell marker; green). [Figure 5-2] See the explanation in Figure 5-1. [Figure 6-1]Figures 6A–6G show in vivo expression of a fluorescent reporter (Figures 6A–6F) and histological images (Figure 6G) obtained by H&E staining 24 hours after subretinal administration of HSV-mCherry. mCherry (red) was co-stained with DAPI (nuclear marker; blue), rhodopsin (RHO; photoreceptor marker; green), and / or isomerohydrolase / RPE65 (retinal pigment epithelial cell (RPEC) marker; green). [Figure 6-2] See the explanation in Figure 6-1. [Figure 7] Figures 7A–7D show the genomic (qPCR) and transcript (qTR-PCR) levels in primary corneal epithelial cells 24 hours (hpi) (Figures 7A–7B) or 48 hours (Figures 7C–7D) of infection with modified herpes simplex virus encoding a proNGF transgene (HSV-proNGF; Figures 7A and 7C) or modified herpes simplex virus encoding a β-NGF transgene (HSV-sNGF; Figures 7B–7D) at a multiple of infection degree (MOI) of 1 or 4. The data are shown in pairs of assayed cells, and the data are presented as mean ± mean standard error (SEM) (n=1). [Figure 8] Figures 8A-8B show Western blot detection of human β-NGF in non-infected control cell medium (mock) or primary corneal epithelial cell medium infected with modified herpes simplex virus encoding the proNGF transgene (HSV-proNGF) at an infection multiplicity (MOI) of 1 or 4. Recombinant human β-NGF was used as a positive control. Figures 8A-8B: Lane 1 Recombinant human β-NGF; Lane 2 Ladder; Lane 3 Mock; Lane 4 HSV-proNGF (MOI=1); Lane 5 HSV-proNGF (MOI 4). Figure 8A: 8-10 ng of total protein was loaded into lanes 4-5. Figure 8B: 115-140 ng of total protein from infected primary corneal epithelial cell culture concentrate was loaded into lanes 4-5. [Figure 9]Figures 9A-9B show the analysis of secreted human β-NGF from primary corneal epithelial cells 48 hours (hpi) after infection with modified herpes simplex virus encoding proNGF (HSV-proNGF; Figure 9A) or modified herpes simplex virus encoding a β-NGF transgene (HSV-sNGF; Figure 9B) at a multiple of infection degree (MOI) of 1 or 4, as determined by ELISA. The data shows cells assayed in pairs, and the data is presented as mean ± mean standard error (SEM) (n=1). [Figure 10] Figures 10A–10B show the viability of primary corneal epithelial cells at 24 hours (hpi) or 48 hours (hpi) after infection with modified herpes simplex virus encoding a proNGF transgene (HSV-proNGF; Figure 10A) or modified herpes simplex virus encoding a β-NGF transgene (HSV-sNGF; Figure 10B) at infection multiples of 0, 0.5, 1, or 3, as analyzed by Mosmann's tetrazolium toxicity (MTT). Data are shown for cells assayed in triplets, and data are presented as mean ± mean standard error (SEM) (n=1). [Figure 11] Figures 11A–11B show cell proliferation (analyzed by cell titer assay) in TF-1 cells 72 hours after treatment with various concentrations of β-NGF, obtained from HEK-293T cells (MOI=4) infected with modified herpes simplex virus encoding a proNGF transgene (HSV-proNGF; Figure 11A) or modified herpes simplex virus encoding a β-NGF transgene (HSV-sNGF; Figure 11B). Medium alone and recombinant human β-NGF were used as controls. Data are shown in triplicates of assayed cells, and data are presented as mean ± mean standard error (SEM) (n=1). [Figure 12] Figures 12A-12C show corneal fluorescence staining of an eye immediately after corneal wound formation (Figure 12A: 1 mm mechanical corneal wound; Figure 12B: 1 mm deeper mechanical corneal wound penetrating the stroma; Figure 12C: cross-hatch needle scratch wound). [Figure 13]Figures 13A-13C show histological images of corneal wound formation and HSV-mCherry infection 24 hours after H&E staining (Figure 13A: 1 mm mechanical corneal wound; Figure 13B: 1 mm deeper mechanical corneal wound; Figure 13C: crosshatch needle scratch wound). [Figure 14] Figures 14A–14D show genome (qPCR; Figures 14A and 14C) and transcript (qRT-PCR; Figures 14B and 14D) in the corneal epithelium (Figures 14A–14B) or the entire eye excluding the corneal epithelium (Figures 14C–14D) 24 hours after topical application of HSV-mCherry to injured eyes. Data are presented as mean ± mean standard error (SEM) (n=3 / group). [Figure 15] Figures 15A–15C show in vivo expression of a fluorescent reporter 24 hours after corneal wound formation and subsequent topical administration of HSV-mCherry (Figure 15A: 1 mm mechanical corneal wound; Figure 15B: 1 mm deeper mechanical corneal wound; Figure 15C: crosshatch needle scratch wound). mCherry (red) was co-stained with DAPI (nuclear marker; blue). [Figure 16] This shows the transduction of HSV-ABCA4 and the expression of the ABCA4 transgene in transduced healthy human ARPE-19 cells (primary retinal pigment epithelial cells). Data are presented as paired mean ± mean standard error (SEM). [Figure 17] This shows the dose-dependent relationship of ABCA4 protein expression (MOI = 0 (mock), 0.05, 0.1, 0.5, 1, or 3) in healthy human ARPE-19 cells transduced with HSV-ABCA4. [Figure 18] Figures 18A–18B show the evaluation of dose-dependent cytotoxicity in healthy human ARPE-19 cells transduced with HSV-ABCA4, analyzed 24 hours (Figure 18A) or 48 hours (Figure 18B) after infection, as measured by Mosmann's tetrazolium toxicity (MTT). Data are presented as triplicate mean ± mean standard error (SEM). [Figure 19]Figures 19A–19C show the analysis of human ABCA4 expression in the eyes of Abca4- / - mice treated with vehicle control (Figure 19A) and HSV-ABCA4 (Figure 19B) 24 hours after choroidal injection, compared to endogenous ABCA4 in wild-type rodent eyes (Figure 19C). Representative images of immunofluorescence (IF) staining of ABCA4 in rodent eyes. Two HSV-ABCA4 treated mice are shown. Panels were imaged at 20× magnification. Nuclei were visualized by DAPI staining. ONL = outer granular layer. [Figure 20] Figures 20A-20B show co-immunofluorescence staining of eye sections from vehicle control (Figure 20A) and HSV-ABCA4 (Figure 20B) treated Abca4- / - mice 24 hours after choroidal injection. Representative images of IF staining for human ABCA4 (red) and mouse rhodopsin (RHO) (green) in Abca4- / - mouse eyes. Panels were 20× magnification images. Nuclei were visualized by DAPI staining (blue). ONL = outer granular layer. [Figure 21] Figures 21A–21H show histological images of eye sections from Abca4- / - mice treated with vehicle control (Figures 21A and 21E) and HSV-ABCA4 (Figures 21B–21D and 21F–21H) 24 hours after suprachoroidal injection. These are representative images of mouse eyes stained with hematoxylin and eosin (H&E). Figures 21A–21D were imaged at 5× magnification, and Figures 21E–21H were imaged at 20× magnification. [Figure 22] Figures 22A-22C show slit-lamp images of the eye before surgery (Figure 22A) and 8 months after surgery and ocular HSV-COL7 treatment (Figure 22B). Figure 22C shows optical coherence tomography (OCT) images of the anterior segment of the corneal epithelium. [Figure 23] This shows a sequential evaluation of visual acuity in the right eye of a patient after local application of HSV-COL7. [Modes for carrying out the invention]

[0027] Detailed explanation The following description illustrates exemplary methods, parameters, and other aspects. However, it should be recognized that such description is not intended to limit the scope of this disclosure, but rather is provided as an illustrative description of exemplary aspects.

[0028] I. General Techniques The techniques and procedures described or referenced herein are generally well understood, for example, Sambrook et al., Molecular Cloning: A Laboratory Manual 3d edition (2001) Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY; Current Protocols in Molecular Biology (FM Ausubel, et al. eds., (2003)); Methods in Enzymology (Academic Press, Inc.) series: PCR 2: A Practical Approach (MJ MacPherson, BD Hames and GR Taylor eds. (1995)), Harlow and Lane, eds. (1988); Oligonucleotide Synthesis (MJ Gait, ed., 1984); Methods in Molecular Biology, Humana Press; Cell Biology: A Laboratory Notebook (JE Cellis, ed., 1998) Academic Press; Animal Cell Culture (RI Freshney), ed., 1987); Introduction to Cell and Tissue Culture (JP Mather and PE Roberts, 1998) Plenum Press; Cell and Tissue Culture: Laboratory Procedures (A. Doyle, JB Griffiths, and DG Newell, eds., 1993-8) J. Wiley and Sons; Gene Transfer Vectors for Mammalian Cells (JM Miller and MP Calos, eds., 1987); PCR: The Polymerase Chain Reaction, (Mullis et al. al.This method is commonly used by those skilled in the art, using conventional methodologies such as the widely used methodologies described in *Short Protocols in Molecular Biology* (Wiley and Sons, 1999).

[0029] II. Definition Before describing this disclosure in detail, it should be understood that this disclosure is not limited to any particular composition or biological system, and that it may, of course, vary. It should also be understood that the terminology used herein is intended to describe only certain aspects and is not intended to limit them.

[0030] As used herein, the singular forms “a,” “an,” and “the” refer to multiple objects unless the context makes it clear otherwise. For example, a reference to “a molecule” may optionally include a combination of two or more such molecules.

[0031] As used herein, the term “and / or” may include any or all combinations of one or more of the related items described. For example, the term “a and / or b” may mean “a alone,” “b alone,” “a or b,” or “a and b”; the term “a, b, and / or c” may mean “a alone,” “b alone,” “c alone,” “a or b,” “a or c,” “b or c,” “a, b, or c,” “a and b,” “a and c,” “b and c,” or “a, b, and c,” etc.

[0032] As used herein, the term “approximately” refers to the normal margin of error for each value, which is readily apparent to those skilled in the art. References to “approximately” values ​​or parameters herein include (and describe) aspects relating to the value or parameter itself.

[0033] The aspects and aspects of this disclosure are understood to include “including,” “being thereof,” and “essentially being thereof.”

[0034] As used herein, the terms “polynucleotide,” “nucleic acid sequence,” “nucleic acid,” and their variations are general to polydeoxyribonucleotides (containing 2-deoxy-D-ribose), polyribonucleotides (containing D-ribose), any other type of polynucleotide that is an N-glycoside of a purine or pyrimidine base, and other polymers containing a non-nucleotide backbone, provided that the polymer contains nucleic acid bases in a configuration that allows for base pairing and base stacking as seen in DNA and RNA. Accordingly, these terms include known types of nucleic acid sequence modifications, e.g., substitution of one or more native nucleotides by analogs, and internucleotide modifications.

[0035] As used herein, nucleic acids are "operatively linked" or "operably linked" if they are in a functional relationship with another nucleic acid sequence. For example, a promoter or enhancer is functionally linked to a coding sequence if it affects the transcription of the sequence, or a ribosome binding site is functionally linked to a coding sequence if it is located to facilitate translation. Generally, "operatively linked" or "operably linked" means that the linked DNA or RNA sequences are in close proximity.

[0036] As used herein, the term “vector” refers to a distinct element used to introduce a heterologous nucleic acid into a cell for its expression or replication. An expression vector includes a vector capable of expressing said nucleic acid, which is functionally linked to a regulatory sequence, such as a promoter region, that can induce the expression of the nucleic acid. Thus, an expression vector may refer to a DNA or RNA construct, such as a plasmid, phage, recombinant virus, or other vector, that results in the expression of a nucleic acid when introduced into a suitable host cell. Suitable expression vectors are well known to those skilled in the art and include vectors that can replicate in eukaryotic cells, as well as vectors that remain in the episome or vectors that are incorporated into the host cell genome.

[0037] As used herein, “open reading frame” or “ORF” refers to a continuous stretch of nucleic acid, either DNA or RNA, that encodes a protein or polypeptide. Typically, the nucleic acid includes a translation start signal or start codon, such as ATG or AUG, and a stop codon.

[0038] As used herein, “untranslated region” or “UTR” refers to the untranslated nucleic acid at the 5’ and / or 3’ ends of an open reading frame. The presence of one or more UTRs in a polynucleotide may affect post-transcriptional regulation, mRNA stability, and / or translation of the polynucleotide.

[0039] As used herein, the term “transgene” refers to a polynucleotide that, after being introduced into a cell, can be transcribed into RNA under appropriate conditions, translated, and / or expressed. In some cases, this confers a desired property to the cell into which it is introduced, or otherwise results in a desired therapeutic or diagnostic outcome.

[0040] As used herein, the terms “polypeptide,” “protein,” and “peptide” are interchangeable and may refer to polymers of two or more amino acids.

[0041] As used herein, “subject,” “host,” or “individual” refers to any animal classified as a mammal, including humans, livestock and farm animals, as well as animals used for exhibition, competition, or as companion animals, such as dogs, horses, cats, and cattle, as well as animals used in research, such as mice, rats, hamsters, rabbits, and non-human primates. In some embodiments, mammals are humans.

[0042] As used herein, the terms “pharmaceutical preparation” or “pharmaceutical composition” mean a preparation in which the biological activity of an active ingredient is enabled, and which does not contain any additional components that are unacceptably toxic to the subject to which the composition or preparation is administered. A “pharmaceutically acceptable” excipient (e.g., vehicle, additive) is one that can be reasonably administered to a target mammal to provide an effective dose of the active ingredient used.

[0043] Where used herein, “effective dose” is the minimum amount necessary to have a measurable improvement or prevention of at least one or more symptoms of a particular disorder. “Effective dose” may vary depending on factors such as the patient’s medical condition, age, sex, and weight. An effective dose is also one in which the therapeutic benefit outweighs any toxic or adverse effects of the treatment. For prophylactic use, beneficial or desired outcomes include eliminating or reducing risk, decreasing severity, or delaying the onset of the disease, its complications, and intermediate pathological phenotypes during the onset of the disease. For therapeutic use, beneficial or desired outcomes include clinical outcomes such as reducing one or more symptoms caused by the disease, improving the quality of life of the person with the disease, reducing the dose of other medicines used to treat the symptoms of the disease, slowing the progression of the disease, and / or extending survival. An effective dose may be administered in one or more doses. For the purposes of this disclosure, an effective dose of recombinant nucleic acid, virus, and / or pharmaceutical composition is an amount sufficient to directly or indirectly achieve a prophylactic or therapeutic treatment. As understood in clinical contexts, the effective dose of recombinant nucleic acids, viruses, and / or pharmaceutical compositions may or may not be achieved in conjunction with other drugs, compounds, or pharmaceutical compositions. Therefore, “effective dose” may be considered in a situation where one or more therapeutic agents are administered, and a single active agent may be considered to be given in an effective dose if the desired outcome can or does occur in conjunction with one or more other active agents.

[0044] As used herein, “treatment” refers to a clinical intervention planned to alter the natural course of the treated individual or cell during the course of clinicopathology. Desired effects of treatment include slowing the rate of disease / disability / deficiency progression, improving or alleviating the state of disease / disability / deficiency, and achieving remission or improving prognosis.

[0045] As used herein, the term “delaying the progression” of a disease / disability / deficiency means postponing, hindering, slowing, delaying, stabilizing, and / or postponing the onset of the disease / disability / deficiency. This delay can be of varying lengths or durations depending on the history of the disease / disability / deficiency and / or the individual being treated. As will be apparent to those skilled in the art, a sufficient or significant delay can encompass prevention in which the individual effectively does not develop the disease.

[0046] III. Recombinant Nucleic Acids Certain aspects of this disclosure relate to recombinant nucleic acids (e.g., isolated recombinant nucleic acids) comprising one or more polynucleotides (e.g., one or more, two or more, three or more, four or more, five or more, ten or more, etc.) encoding polypeptides. In some embodiments, the recombinant nucleic acid comprises one polynucleotide encoding a polypeptide. In some embodiments, the recombinant nucleic acid comprises two polynucleotides encoding polypeptides. In some embodiments, the recombinant nucleic acid comprises three or more polynucleotides encoding polypeptides. In some embodiments, the recombinant nucleic acid comprises one or more polynucleotides encoding two or more polypeptides. In some embodiments, the recombinant nucleic acid comprises two or more polynucleotides encoding two or more polypeptides. In some embodiments, the two or more polypeptides are identical. In some embodiments, the two or more polypeptides are different.

[0047] In some embodiments, the disclosure relates to recombinant nucleic acids comprising polynucleotides encoding a chimeric polypeptide comprising a first polypeptide, a linker polypeptide, and a second polypeptide. In some embodiments, the first and second polypeptides are the same. In some embodiments, the first and second polypeptides are different. In some embodiments, the linker polypeptide is a cleavable linker polypeptide. In some embodiments, the linker polypeptide is a non-cleavable linker polypeptide.

[0048] In some embodiments, recombinant nucleic acid is a vector. In some embodiments, recombinant nucleic acid is a viral vector. In some embodiments, recombinant nucleic acid is a herpesvirus vector. In some embodiments, recombinant nucleic acid is a herpes simplex virus amplicon. In some embodiments, recombinant nucleic acid is a recombinant herpesvirus genome. In some embodiments, the recombinant herpesvirus genome is a recombinant herpes simplex virus genome. In some embodiments, the recombinant herpes simplex virus genome is a recombinant herpes simplex virus type 1 (HSV-1) genome.

[0049] Polynucleotides that encode polypeptides In some aspects, the Disclosure relates to recombinant nucleic acids comprising one or more polynucleotides encoding one or more polypeptides (e.g., one or more human polypeptides). For example, any preferred polypeptide described herein or known in the Art, including human polypeptides, may be encoded by the polynucleotides of the Disclosure.

[0050] In some embodiments, the polynucleotides of this disclosure include the wild-type coding sequence of any gene (including any isoform thereof) described herein or known in the art. In some embodiments, the polynucleotides of this disclosure include codon-optimized variants of the wild-type coding sequence of any gene described herein or known in the art. In some embodiments, the use of codon-optimized variants of the coding sequence of a gene increases the stability and / or yield of heterologous expression (RNA and / or protein) of the encoded polypeptide in target cells compared to the stability and / or yield of heterologous expression of the corresponding non-codon-optimized wild-type sequence. Any preferred method known in the art for performing codon optimization of a sequence for expression in one or more target cells (e.g., one or more human cells) may be used, including, for example, the method described by Fath et al. (PLoS One. 2011 Mar 3;6(3): e17596).

[0051] In some embodiments, the disclosure relates to recombinant nucleic acids comprising one or more polynucleotides containing a coding sequence of a human gene. For example, the SAMD11 gene (see, for example, NCBI Gene ID:148398; SEQ ID NO:378), the NPHP4 gene (see, for example, NCBI Gene ID:261734; SEQ ID NO:379), the ESPN gene (see, for example, NCBI Gene ID:83715; SEQ ID NO:380), the NMNAT1 gene (see, for example, NCBI Gene ID:64802; SEQ ID NO:381), the MFN2 gene (see, for example, NCBI Gene ID:9927; SEQ ID NO:382), the EMC1 gene (see, for example, NCBI Gene ID:23065; SEQ ID NO:383), the PLA2G5 gene (see, for example, NCBI Gene ID:5322; SEQ ID NO:384), the DHDDS gene (see, for example, NCBI Gene ID:79947; SEQ ID See NO:385), PPT1 gene (e.g., see NCBI Gene ID:5538; SEQ ID NO:386), ELOVL1 gene (e.g., see NCBI Gene ID:64834; SEQ ID NO:387), POMGNT1 gene (e.g., see NCBI Gene ID:55624; SEQ ID NO:388), RPE65 gene (e.g., see NCBI Gene ID:6121; SEQ ID NO:389), ABCA4 gene (e.g., see NCBI Gene ID:24; SEQ ID NO:390), COL11A1 gene (e.g., see NCBI Gene ID:1301; SEQ ID NO:391), GNAT2 gene (e.g., see NCBI Gene ID:2780; SEQ ID NO:392), CLCC1 gene (e.g., see NCBI Gene ID:23155; SEQ ID See NO:393), DRAM2 gene (e.g., NCBI Gene ID:128338; see SEQ ID NO:394), PRPF3 gene (e.g., NCBI Gene ID:9129;See SEQ ID NO:395), ENSA gene (e.g., see NCBI Gene ID:2029;SEQ ID NO:396), SEMA4A gene (e.g., see NCBI Gene ID:64218;SEQ ID NO:397), ATF6 gene (e.g., see NCBI Gene ID:22926;SEQ ID NO:398), HMCN1 gene (e.g., see NCBI Gene ID:83872;SEQ ID NO:399), CFH gene (e.g., see NCBI Gene ID:3075;SEQ ID NO:400), CRB1 gene (e.g., see NCBI Gene ID:23418;SEQ ID NO:401), ADIPOR1 gene (e.g., see NCBI Gene ID:51094;SEQ ID NO:402), RD3 gene (e.g., see NCBI Gene ID:343035;SEQ ID See NO:403), NEK2 gene (e.g., see NCBI Gene ID:4751; SEQ ID NO:404), FLVCR1 gene (e.g., see NCBI Gene ID:28982; SEQ ID NO:405), USH2A gene (e.g., see NCBI Gene ID:7399; SEQ ID NO:406), SDCCAG8 gene (e.g., see NCBI Gene ID:10806; SEQ ID NO:407), OR2W3 gene (e.g., see NCBI Gene ID:343171; SEQ ID NO:408), NBAS gene (e.g., see NCBI Gene ID:51594; SEQ ID NO:409), AGBL5 gene (e.g., see NCBI Gene ID:60509; SEQ ID NO:410), ZNF513 gene (e.g., see NCBI Gene ID:130557; SEQ ID See NO:411), IFT172 gene (e.g., NCBI Gene ID:26160; see SEQ ID NO:412), PCARE gene (e.g., NCBI Gene ID:388939;See SEQ ID NO:413), EFEMP1 / TLE5 gene (e.g., see NCBI Gene ID:2202;SEQ ID NO:414), FAM161A gene (e.g., see NCBI Gene ID:84140;SEQ ID NO:415), WDPCP gene (e.g., see NCBI Gene ID:51057;SEQ ID NO:416), ALMS1 gene (e.g., see NCBI Gene ID:7840;SEQ ID NO:417), SNRNP200 gene (e.g., see NCBI Gene ID:23020;SEQ ID NO:418), CNNM4 gene (e.g., see NCBI Gene ID:26504;SEQ ID NO:419), CNGA3 gene (e.g., see NCBI Gene ID:1261;SEQ ID NO:420), NPHP1 gene (e.g., see NCBI Gene See ID:4867;SEQ ID NO:421), MERTK gene (see, for example, NCBI Gene ID:10461;SEQ ID NO:422), BBS5 gene (see, for example, NCBI Gene ID:129880;SEQ ID NO:423), CERKL gene (see, for example, NCBI Gene ID:375298;SEQ ID NO:424), NEUROD1 gene (see, for example, NCBI Gene ID:4760;SEQ ID NO:425), TMEM237 gene (see, for example, NCBI Gene ID:65062;SEQ ID NO:426), KCNJ13 gene (see, for example, NCBI Gene ID:3769;SEQ ID NO:427), SAG gene (see, for example, NCBI Gene ID:6295;SEQ ID NO:428), SPP2 gene (see, for example, NCBI Gene See ID:6694;SEQ ID NO:429), TRNT1 gene (e.g., see NCBI Gene ID:51095;SEQ ID NO:430), SLC4A7 gene (e.g., NCBI Gene ID:9497;See SEQ ID NO:431), LZTFL1 gene (e.g., see NCBI Gene ID:54585;SEQ ID NO:432), GNAT1 gene (e.g., see NCBI Gene ID:2779;SEQ ID NO:433), TREX1 gene (e.g., see NCBI Gene ID:11277;SEQ ID NO:434), MAPKAPK3 gene (e.g., see NCBI Gene ID:7867;SEQ ID NO:435), ATXN7 gene (e.g., see NCBI Gene ID:6314;SEQ ID NO:436), PROS1 gene (e.g., see NCBI Gene ID:5627;SEQ ID NO:437), ARL6 gene (e.g., see NCBI Gene ID:84100;SEQ ID NO:438), IMPG2 gene (e.g., see NCBI Gene ID:50939;SEQ ID See NO:439), IQCB1 gene (e.g., see NCBI Gene ID:9657; SEQ ID NO:440), RHO gene (e.g., see NCBI Gene ID:6010; SEQ ID NO:441), NPHP3 gene (e.g., see NCBI Gene ID:27031; SEQ ID NO:442), CLRN1 gene (e.g., see NCBI Gene ID:7401; SEQ ID NO:443), SLC7A14 gene (e.g., see NCBI Gene ID:57709; SEQ ID NO:444), PCYT1A gene (e.g., see NCBI Gene ID:5130; SEQ ID NO:445), CEP19 gene (e.g., see NCBI Gene ID:84984; SEQ ID NO:446), PDE6B gene (e.g., see NCBI Gene ID:5158; SEQ ID See NO:447), WFS1 gene (e.g., see NCBI Gene ID:7466; SEQ ID NO:448), HMX1 gene (e.g., see NCBI Gene ID:3166; SEQ ID NO:449), RAB28 gene (e.g., NCBI Gene ID:9364;See SEQ ID NO:450), CC2D2A gene (e.g., see NCBI Gene ID:57545;SEQ ID NO:451), PROM1 gene (e.g., see NCBI Gene ID:8842;SEQ ID NO:452), ADGRA3 gene (e.g., see NCBI Gene ID:166647;SEQ ID NO:453), DTHD1 gene (e.g., see NCBI Gene ID:401124;SEQ ID NO:454), WDR19 gene (e.g., see NCBI Gene ID:57728;SEQ ID NO:455), CNGA1 gene (e.g., see NCBI Gene ID:1259;SEQ ID NO:456), CISD2 gene (e.g., see NCBI Gene ID:493856;SEQ ID NO:457), MTTP gene (e.g., see NCBI Gene ID:4547;SEQ ID See NO:458), LRIT3 gene (e.g., see NCBI Gene ID:345193; SEQ ID NO:459), BBS7 gene (e.g., see NCBI Gene ID:55212; SEQ ID NO:460), BBS12 gene (e.g., see NCBI Gene ID:166379; SEQ ID NO:461), MFSD8 gene (e.g., see NCBI Gene ID:256471; SEQ ID NO:462), PLK4 gene (e.g., see NCBI Gene ID:10733; SEQ ID NO:463), LRAT gene (e.g., see NCBI Gene ID:9227; SEQ ID NO:464), TLR3 gene (e.g., see NCBI Gene ID:7098; SEQ ID NO:465), CYP4V2 gene (e.g., see NCBI Gene ID:285440; SEQ ID See NO:466), CWC27 gene (e.g., NCBI Gene ID:10283; see SEQ ID NO:467), POC5 gene (e.g., NCBI Gene ID:134359;See SEQ ID NO:468), VCAN gene (e.g., see NCBI Gene ID:1462;SEQ ID NO:469), ADGRV1 gene (e.g., see NCBI Gene ID:84059;SEQ ID NO:470), NR2F1 gene (e.g., see NCBI Gene ID:7025;SEQ ID NO:471), SLC25A46 gene (e.g., see NCBI Gene ID:91137;SEQ ID NO:472), CTNNA1 gene (e.g., see NCBI Gene ID:1495;SEQ ID NO:473), HARS1 gene (e.g., see NCBI Gene ID:3035;SEQ ID NO:474), PDE6A gene (e.g., see NCBI Gene ID:5145;SEQ ID NO:475), GRM6 gene (e.g., see NCBI Gene ID:2916;SEQ ID See NO:476), MAK gene (e.g., see NCBI Gene ID:4117; SEQ ID NO:477), C2 gene (e.g., see NCBI Gene ID:717; SEQ ID NO:478), CFB gene (e.g., see NCBI Gene ID:629; SEQ ID NO:479), TULP1 gene (e.g., see NCBI Gene ID:7287; SEQ ID NO:480), GUCA1A gene (e.g., see NCBI Gene ID:2978; SEQ ID NO:481), GUCA1B gene (e.g., see NCBI Gene ID:2979; SEQ ID NO:482), PRPH2 gene (e.g., see NCBI Gene ID:5961; SEQ ID NO:483), IMPG1 gene (e.g., see NCBI Gene ID:3617; SEQ ID NO:484), EYS gene (e.g., see NCBI See Gene ID:346007;SEQ ID NO:485), COL9A1 gene (see, for example, NCBI Gene ID:1297;SEQ ID NO:486), RIMS1 gene (see, for example, NCBI Gene ID:22999;See SEQ ID NO:487), LCA5 gene (e.g., see NCBI Gene ID:167691;SEQ ID NO:488), ELOVL4 gene (e.g., see NCBI Gene ID:6785;SEQ ID NO:489), PRDM13 gene (e.g., see NCBI Gene ID:59336;SEQ ID NO:490), RTN4IP1 gene (e.g., see NCBI Gene ID:84816;SEQ ID NO:491), AHI1 gene (e.g., see NCBI Gene ID:54806;SEQ ID NO:492), PEX7 gene (e.g., see NCBI Gene ID:5191;SEQ ID NO:493), CNOT9 gene (e.g., see NCBI Gene ID:9125;SEQ ID NO:494), AHR gene (e.g., see NCBI Gene ID:196;SEQ ID See NO:495), KLHL7 gene (e.g., see NCBI Gene ID:55975; SEQ ID NO:496), RP9 gene (e.g., see NCBI Gene ID:6100; SEQ ID NO:497), BBS9 gene (e.g., see NCBI Gene ID:27241; SEQ ID NO:498), PEX1 gene (e.g., see NCBI Gene ID:5189; SEQ ID NO:499), TSPAN12 gene (e.g., see NCBI Gene ID:23554; SEQ ID NO:500), IMPDH1 gene (e.g., see NCBI Gene ID:3614; SEQ ID NO:501), OPN1SW gene (e.g., see NCBI Gene ID:611; SEQ ID NO:502), KIAA1549 gene (e.g., see NCBI Gene ID:57670; SEQ ID See NO:503), RP1L1 gene (e.g., NCBI Gene ID:94137; see SEQ ID NO:504), ADAM9 gene (e.g., NCBI Gene ID:8754; see SEQ ID NO:505), HGSNAT gene (e.g., NCBI Gene ID:138050;See SEQ ID NO:506), RP1 gene (e.g., see NCBI Gene ID:6101;SEQ ID NO:507), TTPA gene (e.g., see NCBI Gene ID:7274;SEQ ID NO:508), CSPP1 gene (e.g., see NCBI Gene ID:79848;SEQ ID NO:509), OPA1 gene (e.g., see NCBI Gene ID:4976;SEQ ID NO:510), PEX2 gene (e.g., see NCBI Gene ID:5828;SEQ ID NO:511), CNGB3 gene (e.g., see NCBI Gene ID:54714;SEQ ID NO:512), CFAP418 gene (e.g., see NCBI Gene ID:157657;SEQ ID NO:513), GDF6 gene (e.g., see NCBI Gene ID:392255;SEQ ID See NO:514), RIMS2 gene (e.g., see NCBI Gene ID:9699; SEQ ID NO:515), KCNV2 gene (e.g., see NCBI Gene ID:169522; SEQ ID NO:516), TOPORS gene (e.g., see NCBI Gene ID:10210; SEQ ID NO:517), CEP78 gene (e.g., see NCBI Gene ID:84131; See SEQ ID NO:518), INVS gene (e.g., see NCBI Gene ID:27130;SEQ ID NO:519), PRPF4 gene (e.g., see NCBI Gene ID:9128;SEQ ID NO:520), WHRN gene (e.g., see NCBI Gene ID:25861;SEQ ID NO:521), TRIM32 gene (e.g., see NCBI Gene ID:22954;SEQ ID NO:522), TLR4 gene (e.g., see NCBI Gene ID:7099;SEQ ID NO:523), DYNC2I2 gene (e.g., see NCBI Gene ID:89891;SEQ ID NO:524), PDCD2 gene (e.g., see NCBI Gene ID:5134;SEQ ID NO:525), EXOSC2 gene (e.g., see NCBI Gene ID:23404;SEQ ID See NO:526), ​​INPP5E gene (e.g., see NCBI Gene ID:56623; SEQ ID NO:527), PHYH gene (e.g., see NCBI Gene ID:5264; SEQ ID NO:528), ACBD5 gene (e.g., see NCBI Gene ID:91452; SEQ ID NO:529), PCDH15 gene (e.g., see NCBI Gene ID:65217; SEQ ID NO:530), RBP3 gene (e.g., see NCBI Gene ID:5949; SEQ ID NO:531), ERCC6 gene (e.g., see NCBI Gene ID:2074; SEQ ID NO:532), HK1 gene (e.g., see NCBI Gene ID:3098; SEQ ID NO:533), CDH23 gene (e.g., see NCBI Gene ID:64072; SEQ ID See NO:534), CDHR1 gene (e.g., NCBI Gene ID:92211; see SEQ ID NO:535), RGR gene (e.g., NCBI Gene ID:5995; see SEQ ID NO:536), KIF11 gene (e.g., NCBI Gene ID:3832;See SEQ ID NO:537), RBP4 gene (e.g., see NCBI Gene ID:5950;SEQ ID NO:538), PDE6C gene (e.g., see NCBI Gene ID:5146;SEQ ID NO:539), PAX2 gene (e.g., see NCBI Gene ID:5076;SEQ ID NO:540), PDZD7 gene (e.g., see NCBI Gene ID:79955;SEQ ID NO:541), ARL3 gene (e.g., see NCBI Gene ID:403;SEQ ID NO:542), BBIP1 gene (e.g., see NCBI Gene ID:92482;SEQ ID NO:543), ARMS2 gene (e.g., see NCBI Gene ID:387715;SEQ ID NO:544), HTRA1 gene (e.g., see NCBI Gene ID:5654;SEQ ID See NO:545), OAT gene (e.g., see NCBI Gene ID:4942; SEQ ID NO:546), ZNF408 gene (e.g., see NCBI Gene ID:79797; SEQ ID NO:547), TUB gene (e.g., see NCBI Gene ID:7275; SEQ ID NO:548), TEAD1 gene (e.g., see NCBI Gene ID:7003; SEQ ID NO:549), USH1C gene (e.g., see NCBI Gene ID:10083; SEQ ID NO:550), TMEM216 gene (e.g., see NCBI Gene ID:51259; SEQ ID NO:551), BEST1 gene (e.g., see NCBI Gene ID:7439; SEQ ID NO:552), ASRGL1 gene (e.g., see NCBI Gene ID:80150; SEQ ID See NO:553), ROM1 gene (e.g., see NCBI Gene ID:6094; SEQ ID NO:554), BBS1 gene (e.g., see NCBI Gene ID:582; SEQ ID NO:555), CABP4 gene (e.g., NCBI Gene ID:57010;See SEQ ID NO:556), LRP5 gene (e.g., see NCBI Gene ID:4041;SEQ ID NO:557), CAPN5 gene (e.g., see NCBI Gene ID:726;SEQ ID NO:558), MYO7A gene (e.g., see NCBI Gene ID:4647;SEQ ID NO:559), TMEM126A gene (e.g., see NCBI Gene ID:84233;SEQ ID NO:560), FZD4 gene (e.g., see NCBI Gene ID:8322;SEQ ID NO:561), DYNC2LI1 gene (e.g., see NCBI Gene ID:51626;SEQ ID NO:562), CEP164 gene (e.g., see NCBI Gene ID:22897;SEQ ID NO:563), C1QTNF5 gene (e.g., see NCBI Gene See ID:114902;SEQ ID NO:564), MFRP gene (see, for example, NCBI Gene ID:83552;SEQ ID NO:565), CACNA2D4 gene (see, for example, NCBI Gene ID:93589;SEQ ID NO:566), GNB3 gene (see, for example, NCBI Gene ID:2784;SEQ ID NO:567), PDE6H gene (see, for example, NCBI Gene ID:5149;SEQ ID NO:568), COL2A1 gene (see, for example, NCBI Gene ID:1280;SEQ ID NO:569), MMP19 gene (see, for example, NCBI Gene ID:4327;SEQ ID NO:570), RDH5 gene (see, for example, NCBI Gene ID:5959;SEQ ID NO:571), CCT2 gene (see, for example, NCBI Gene See ID:10576;SEQ ID NO:572), BBS10 gene (e.g., see NCBI Gene ID:79738;SEQ ID NO:573), CEP290 gene (e.g., NCBI Gene ID:80184;See SEQ ID NO:574), POC1B gene (e.g., see NCBI Gene ID:282809;SEQ ID NO:575), MVK gene (e.g., see NCBI Gene ID:4598;SEQ ID NO:576), IFT81 gene (e.g., see NCBI Gene ID:28981;SEQ ID NO:577), MTRFR gene (e.g., see NCBI Gene ID:91574;SEQ ID NO:578), ITM2B gene (e.g., see NCBI Gene ID:9445;SEQ ID NO:579), RB1 gene (e.g., see NCBI Gene ID:5925;SEQ ID NO:580), RCBTB1 gene (e.g., see NCBI Gene ID:55213;SEQ ID NO:581), GRK1 gene (e.g., see NCBI Gene ID:6011;SEQ ID See NO:582), RPGRIP1 gene (e.g., see NCBI Gene ID:57096; SEQ ID NO:583), NRL gene (e.g., see NCBI Gene ID:4901; SEQ ID NO:584), OTX2 gene (e.g., see NCBI Gene ID:5015; SEQ ID NO:585), RDH11 gene (e.g., see NCBI Gene ID:51109; SEQ ID NO:585), RDH12 gene (e.g., see NCBI Gene ID:145226; SEQ ID NO:587), TTLL5 gene (e.g., see NCBI Gene ID:23093; SEQ ID NO:588), SPATA7 gene (e.g., see NCBI Gene ID:55812; SEQ ID NO:589), TTC8 gene (e.g., see NCBI Gene ID:123016; SEQ ID See NO:590), FBLN5 gene (e.g., NCBI Gene ID:10516; see SEQ ID NO:591), TRPM1 gene (e.g., NCBI Gene ID:4308; see SEQ ID NO:592), TUBGCP4 gene (e.g., NCBI Gene ID:27229;See SEQ ID NO:593), SLC24A1 gene (e.g., see NCBI Gene ID:9187;SEQ ID NO:594), NR2E3 gene (e.g., see NCBI Gene ID:10002;SEQ ID NO:595), BBS4 gene (e.g., see NCBI Gene ID:585;SEQ ID NO:596), CIB2 gene (e.g., see NCBI Gene ID:10518;SEQ ID NO:597), RLBP1 gene (e.g., see NCBI Gene ID:6017;SEQ ID NO:598), GNPTG gene (e.g., see NCBI Gene ID:84572;SEQ ID NO:599), IFT140 gene (e.g., see NCBI Gene ID:9742;SEQ ID NO:600), CLUAP1 gene (e.g., see NCBI Gene ID:23059;SEQ ID See NO:601), ABCC6 gene (e.g., see NCBI Gene ID:368; SEQ ID NO:602), CRYM gene (e.g., see NCBI Gene ID:1428; SEQ ID NO:603), CLN3 gene (e.g., see NCBI Gene ID:1201; SEQ ID NO:604), ZNF423 gene (e.g., see NCBI Gene ID:23090; SEQ ID NO:605), RPGRIP1L gene (e.g., see NCBI Gene ID:23322; SEQ ID NO:606), BBS2 gene (e.g., see NCBI Gene ID:583; SEQ ID NO:607), ARL2BP gene (e.g., see NCBI Gene ID:23568; SEQ ID NO:608), CNGB1 gene (e.g., see NCBI Gene ID:1258; SEQ ID See NO:609), CDH3 gene (e.g., see NCBI Gene ID:1001; SEQ ID NO:610), DHX38 gene (e.g., see NCBI Gene ID:9785; SEQ ID NO:611), ADAMTS18 gene (e.g., see NCBI Gene ID:170692;See SEQ ID NO:612), SLC38A8 gene (e.g., NCBI Gene ID:146167; SEQ ID NO:613), GUCY2D gene (e.g., NCBI Gene ID:3000; SEQ ID NO:614), PRPF8 gene (e.g., NCBI Gene ID:10594; SEQ ID NO:615), AIPL1 gene (e.g., NCBI Gene ID:23746; SEQ ID NO:616), PITPNM3 gene (e.g., NCBI Gene ID:83394; SEQ ID NO:617), UNC119 gene (e.g., NCBI Gene ID:9094; SEQ ID NO:618), GPR179 gene (e.g., NCBI Gene ID:440435; SEQ ID NO:619), MKS1 gene (e.g., NCBI Gene See ID:54903;SEQ ID NO:620), CA4 gene (see, for example, NCBI Gene ID:762;SEQ ID NO:621), RGS9 gene (see, for example, NCBI Gene ID:8787;SEQ ID NO:622), ARSG gene (see, for example, NCBI Gene ID:22901;SEQ ID NO:623), USH1G gene (see, for example, NCBI Gene ID:124590;SEQ ID NO:624), PRCD gene (see, for example, NCBI Gene ID:768206;SEQ ID NO:625), FSCN2 gene (see, for example, NCBI Gene ID:25794;SEQ ID NO:626), PDE6G gene (see, for example, NCBI Gene ID:5148;SEQ ID NO:627), LAMA1 gene (see, for example, NCBI Gene See ID:284217;SEQ ID NO:628), AFG3L2 gene (e.g., see NCBI Gene ID:10939;SEQ ID NO:629), CRX gene (e.g., NCBI Gene ID:1406;See SEQ ID NO:630), REEP6 gene (e.g., see NCBI Gene ID:92840;SEQ ID NO:631), RAX2 gene (e.g., see NCBI Gene ID:84839;SEQ ID NO:632), C3 gene (e.g., see NCBI Gene ID:718;SEQ ID NO:633), ARHGEF18 gene (e.g., see NCBI Gene ID:23370;SEQ ID NO:634), PNPLA6 gene (e.g., see NCBI Gene ID:10908;SEQ ID NO:635), RGS9BP gene (e.g., see NCBI Gene ID:388531;SEQ ID NO:636), OPA3 gene (e.g., see NCBI Gene ID:80207;SEQ ID NO:637), PRPF31 gene (e.g., see NCBI Gene ID:26121;SEQ ID See NO:638), IDH3B gene (e.g., see NCBI Gene ID:3420; SEQ ID NO:639), PANK2 gene (e.g., see NCBI Gene ID:80025; SEQ ID NO:640), JAG1 gene (e.g., see NCBI Gene ID:182; SEQ ID NO:641), MKKS gene (e.g., see NCBI Gene ID:8195; SEQ ID NO:642), KIZ gene (e.g., see NCBI Gene ID:55857; SEQ ID NO:643), ABHD12 gene (e.g., see NCBI Gene ID:26090; SEQ ID NO:644), KIF3B gene (e.g., see NCBI Gene ID:9371; SEQ ID NO:645), CEP250 gene (e.g., see NCBI Gene ID:11190; SEQ ID See NO:646), PRPF6 gene (e.g., see NCBI Gene ID:24148; SEQ ID NO:647), CFAP410 gene (e.g., see NCBI Gene ID:755; SEQ ID NO:648), DNM1L gene (e.g., see NCBI Gene ID:10059;See SEQ ID NO:649), TIMP3 gene (e.g., NCBI Gene ID:7078; SEQ ID NO:650), IFT27 gene (e.g., NCBI Gene ID:11020; SEQ ID NO:651), FBLN1 gene (e.g., NCBI Gene ID:2192; SEQ ID NO:652), MIEF1 gene (e.g., NCBI Gene ID:; SEQ ID NO:653), ACO2 gene (e.g., NCBI Gene ID:50; SEQ ID NO:654), TUBGCP6 gene (e.g., NCBI Gene ID:85378; SEQ ID NO:655), OFD1 gene (e.g., NCBI Gene ID:8481; SEQ ID NO:656), RS1 gene (e.g., NCBI Gene ID:6247; SEQ ID See NO:657), RP2 gene (e.g., see NCBI Gene ID:6102; SEQ ID NO:658), DMD gene (e.g., see NCBI Gene ID:1756; SEQ ID NO:659), RPGR gene (e.g., see NCBI Gene ID:6103; SEQ ID NO:660), NYX gene (e.g., see NCBI Gene I; See D:60506;SEQ ID NO:661), PEPD gene (see, for example, NCBI Gene ID:5184;SEQ ID NO:662), NDP gene (see, for example, NCBI Gene ID:4693;SEQ ID NO:663), CACNA1F gene (see, for example, NCBI Gene ID:778;SEQ ID NO:664), PGK1 gene (see, for example, NCBI Gene ID:5230;SEQ ID NO:665), CHM gene (see, for example, NCBI Gene ID:1121;SEQ ID NO:666), TIMM8A gene (see, for example, NCBI Gene ID:1678;SEQ ID NO:667), PRPS1 gene (see, for example, NCBI Gene ID:5631;SEQ ID NO:668), OPN1LW gene (see, for example, NCBI Gene ID:5956;SEQ ID See NO:669), OPN1MW gene (e.g., see NCBI Gene ID:2652; SEQ ID NO:670), OPN1SW gene (e.g., see NCBI Gene ID:611; SEQ ID NO:671), TFAM gene (e.g., see NCBI Gene ID:7019; SEQ ID NO:672), MT-ND1 gene (e.g., see NCBI Gene ID:4535; SEQ ID NO:673), MT-ND2 gene (e.g., see NCBI Gene ID:4536; SEQ ID NO:674), MT-ND3 gene (e.g., see NCBI Gene ID:4537; SEQ ID NO:675), MT-ND4L gene (e.g., see NCBI Gene ID:4539; SEQ ID NO:676), MT-ND4 gene (e.g., see NCBI Gene ID:4538; SEQ ID See NO:677), MT-ND5 gene (e.g., NCBI Gene ID:4540; see SEQ ID NO:678), MT-ND6 gene (e.g., NCBI Gene ID:4541;See SEQ ID NO:679), MT-ATP6 gene (e.g., see NCBI Gene ID:4508;SEQ ID NO:680), MT-ATP8 gene (e.g., see NCBI Gene ID:4509;SEQ ID NO:681), MT-CO1 gene (e.g., see NCBI Gene ID:4512;SEQ ID NO:682), MT-CO3 gene (e.g., see NCBI Gene ID:4514;SEQ ID NO:683), MT-CYB gene (e.g., see NCBI Gene ID:4519;SEQ ID NO:684), LARS2 gene (e.g., see NCBI Gene ID:23395;SEQ ID NO:685), EARS2 gene (e.g., see NCBI Gene ID:124454;SEQ ID NO:686), KARS1 gene (e.g., see NCBI Gene ID:3735;SEQ ID See NO:687), HARS2 gene (e.g., see NCBI Gene ID:23438; SEQ ID NO:688), SARS2 gene (e.g., see NCBI Gene ID:54938; SEQ ID NO:689), PARS2 gene (e.g., see NCBI Gene ID:25973; SEQ ID NO:690), MMACHC gene (e.g., see NCBI Gene ID:25974; SEQ ID NO:691), POU3F4 gene (e.g., see NCBI Gene ID:5456; SEQ ID NO:692), RPS6KA6 gene (e.g., see NCBI Gene ID:27330; SEQ ID NO:693), CPLANE1 gene (e.g., see NCBI Gene ID:65250; SEQ ID NO:694), TMEM67 gene (e.g., see NCBI Gene ID:91147; SEQ ID See NO:695), TRAF3IP1 gene (e.g., NCBI Gene ID:26146; see SEQ ID NO:696), IFT74 gene (e.g., NCBI Gene ID:80173;See SEQ ID NO:697), SCAPER gene (e.g., see NCBI Gene ID:49855;SEQ ID NO:698), SCLT1 gene (e.g., see NCBI Gene ID:132320;SEQ ID NO:699), KIAA0586 gene (e.g., see NCBI Gene ID:9786;SEQ ID NO:700), TCTN2 gene (e.g., see NCBI Gene ID:79867;SEQ ID NO:701), ARL13B gene (e.g., see NCBI Gene ID:200894;SEQ ID NO:702), B9D1 gene (e.g., see NCBI Gene ID:27077;SEQ ID NO:703), B9D2 gene (e.g., see NCBI Gene ID:80776;SEQ ID NO:704), C2CD3 gene (e.g., see NCBI Gene See ID:26005;SEQ ID NO:705), CEP41 gene (see, for example, NCBI Gene ID:95681;SEQ ID NO:706), CEP104 gene (see, for example, NCBI Gene ID:9731;SEQ ID NO:707), CEP120 gene (see, for example, NCBI Gene ID:153241;SEQ ID NO:708), IFT172 gene (see, for example, NCBI Gene ID:26160;SEQ ID NO:709), KATNIP gene (see, for example, NCBI Gene ID:23247;SEQ ID NO:710), KIF7 gene (see, for example, NCBI Gene ID:374654;SEQ ID NO:711), PDE6D gene (see, for example, NCBI Gene ID:5147;SEQ ID See NO:712), TCTN1 gene (e.g., see NCBI Gene ID:79600; SEQ ID NO:713), TCTN3 gene (e.g., see NCBI Gene ID:26123; SEQ ID NO:714), TMEM107 gene (e.g., see NCBI Gene ID:84314;See SEQ ID NO:715), TMEM138 gene (e.g., see NCBI Gene ID:51524;SEQ ID NO:716), TMEM231 gene (e.g., see NCBI Gene ID:79583;SEQ ID NO:717), TTC21B gene (e.g., see NCBI Gene ID:79809;SEQ ID NO:718), RORA gene (e.g., see NCBI Gene ID:6095;SEQ ID NO:719), NGF gene (e.g., see NCBI Gene ID:4803;SEQ ID NO:720), COL8A2 gene (e.g., see NCBI Gene ID:1296;SEQ ID NO:721), SLC4A11 gene (e.g., see NCBI Gene ID:83959;SEQ ID NO:722), ZEB1 gene (e.g., see NCBI Gene ID:6935;SEQ See ID NO:723), KRT83 gene (e.g., see NCBI Gene ID:3889; SEQ ID NO:724), KRT12 gene (e.g., see NCBI Gene ID:3859; SEQ ID NO:725), TGFBI gene (e.g., see NCBI Gene ID:7045; SEQ ID NO:726), TACSTD2 gene (e.g., see NCBI Gene ID:4070; SEQ ID NO:727), CHST6 gene (e.g., see NCBI Gene ID:4166; SEQ ID NO:728), GSN gene (e.g., see NCBI Gene ID:2934; SEQ ID NO:729), UBIAD1 gene (e.g., see NCBI Gene ID:29914; SEQ ID NO:730), DCN gene (e.g., see NCBI Gene ID:1634; SEQ ID See NO:731), PIKFYVE gene (e.g., NCBI Gene ID:200576; see SEQ ID NO:732), OVOL2 gene (e.g., NCBI Gene ID:58495;Any suitable human gene known in the art (including any isoform thereof), including the GRHL2 gene (see, for example, NCBI Gene ID: 79977; SEQ ID NO: 734), can be encoded by the polynucleotides of this disclosure. In some embodiments, the polynucleotides of this disclosure include sequences having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to any of the human genes (and / or coding sequences thereof) described herein or known in the art.

[0052] In some embodiments, the polynucleotides of the Disclosure encode β-nerve growth factor polypeptides. In some embodiments, the β-nerve growth factor polypeptide is a human β-nerve growth factor polypeptide (see, for example, UniProt accession number: P01138). In some embodiments, the polynucleotide comprises a coding sequence of the wild-type NGF gene (see, for example, NCBI Gene ID: 4803, SEQ ID NO: 720) or a codon-optimized variant thereof (see, for example, SEQ ID NO: 735, SEQ ID NO: 736, SEQ ID NO: 741, SEQ ID NO: 742, and / or SEQ ID NO: 743). In some embodiments, the polynucleotide encoding the β-nerve growth factor polypeptide is a polynucleotide encoding a polypeptide comprising an amino acid sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity with respect to the sequence of SEQ ID NO:363.

[0053] In some embodiments, the polynucleotides of the Disclosure encode β-nerve growth factor polypeptides. In some embodiments, the β-nerve growth factor polypeptide is a human β-nerve growth factor polypeptide (see, for example, UniProt accession number: P01138). In some embodiments, the polynucleotide comprises a coding sequence of the wild-type NGF gene (see, for example, NCBI Gene ID: 4803, SEQ ID NO: 720) or a codon-optimized variant thereof (see, for example, SIEQ ID NO: 735, SEQ ID NO: 736, SEQ ID NO: 741, SEQ ID NO: 742, and / or SEQ ID NO: 743). In some embodiments, the polynucleotide encoding the β-nerve growth factor polypeptide is a polynucleotide encoding a polypeptide comprising an amino acid sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity with respect to the sequence of SEQ ID NO:739.

[0054] In some embodiments, the polynucleotides of the Disclosure encode β-nerve growth factor polypeptides. In some embodiments, the β-nerve growth factor polypeptide is a human β-nerve growth factor polypeptide (see, for example, UniProt accession number: P01138). In some embodiments, the polynucleotide comprises a coding sequence of the wild-type NGF gene (see, for example, NCBI Gene ID: 4803, SEQ ID NO: 720) or a codon-optimized variant thereof (see, for example, SIEQ ID NO: 735, SEQ ID NO: 736, SEQ ID NO: 741, SEQ ID NO: 742, and / or SEQ ID NO: 743). In some embodiments, the polynucleotide encoding the β-nerve growth factor polypeptide is a polynucleotide encoding a polypeptide comprising an amino acid sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity with respect to the sequence of SEQ ID NO:740.

[0055] In some embodiments, the polynucleotide encoding the β-nerve growth factor polypeptide is a polynucleotide encoding an N-terminal cleavage, C-terminal cleavage, or fragment of the amino acid sequence of SEQ ID NO:363, SEQ ID NO:739, and / or SEQ ID NO:740. The N-terminal cleavage, C-terminal cleavage, or fragment may contain at least 10, at least 12, at least 14, at least 16, at least 18, at least 20, at least 30, at least 40, at least 50, at least 75, at least 100, or at least 200 consecutive amino acids of SEQ ID NO:363, SEQ ID NO:739, and / or SEQ ID NO:740, but fewer than 241 consecutive amino acids.

[0056] In some embodiments, the polynucleotides of the present disclosure encode a retina-specific phospholipid transport ATPase polypeptide. In some embodiments, the retina-specific phospholipid transport ATPase polypeptide is a human retina-specific phospholipid transport ATPase polypeptide (see, for example, UniProt accession number: P78363). In some embodiments, the polynucleotide comprises the coding sequence of the wild-type ABCA4 gene (see, for example, NCBI Gene ID: 24, SEQ ID NO: 390) or a codon-optimized variant thereof (see, for example, SEQ ID NO: 737). In some embodiments, the polynucleotide encoding the retina-specific phospholipid transport ATPase polypeptide is a polynucleotide encoding a polypeptide comprising an amino acid sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity with respect to the sequence of SEQ ID NO:33.

[0057] In some embodiments, the polynucleotide encoding the retina-specific phospholipid transport ATPase polypeptide is a polynucleotide encoding an N-terminal cleavage, C-terminal cleavage, or fragment of the amino acid sequence of SEQ ID NO:33. The N-terminal cleavage, C-terminal cleavage, or fragment may contain at least 10, at least 12, at least 14, at least 16, at least 18, at least 20, at least 30, at least 40, at least 50, at least 75, at least 100, at least 200, at least 300, at least 400, at least 500, at least 600, at least 700, at least 800, at least 900, or at least 1,000 consecutive amino acids of SEQ ID NO:33, but fewer than 2,273.

[0058] In some embodiments, the polynucleotides of the present disclosure encode a centrosome protein 290 kDa polypeptide. In some embodiments, the centrosome protein 290 kDa polypeptide is a human centrosome protein 290 kDa polypeptide (see, for example, UniProt accession number: O15078). In some embodiments, the polynucleotide comprises the coding sequence of the wild-type CEP290 gene (see, for example, NCBI Gene ID: 80184, SEQ ID NO: 574) or a codon-optimized variant thereof (see, for example, SEQ ID NO: 738). In some embodiments, the polynucleotide encoding the centrosome protein 290kDa polypeptide is a polynucleotide encoding a polypeptide comprising an amino acid sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity with respect to the sequence of SEQ ID NO:217.

[0059] In some embodiments, the polynucleotide encoding the centrosome protein 290 kDa polypeptide is a polynucleotide encoding an N-terminal cleavage, C-terminal cleavage, or fragment of the amino acid sequence of SEQ ID NO:217. The N-terminal cleavage, C-terminal cleavage, or fragment may contain at least 10, at least 12, at least 14, at least 16, at least 18, at least 20, at least 30, at least 40, at least 50, at least 75, at least 100, at least 200, at least 300, at least 400, at least 500, at least 600, at least 700, at least 800, at least 900, or at least 1,000 consecutive amino acids of SEQ ID NO:217, but fewer than 2,479.

[0060] In some embodiments, the polynucleotides of the present disclosure encode polypeptides. In some embodiments, the polypeptides are human polypeptides. In some embodiments, the polynucleotides include a coding sequence of a wild-type gene (see, e.g., SEQ ID NO: 378-734) or a codon-optimized variant thereof (see, e.g., SEQ ID NO: 735-738 and / or SEQ ID NO: 741-743). In some embodiments, the polynucleotide encoding a polypeptide is a polynucleotide encoding a polypeptide comprising an amino acid sequence having at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity with an amino acid sequence selected from SEQ ID NO: 21-377 and / or SEQ ID NO: 739-740. In some embodiments, the polynucleotides of the present disclosure encode polypeptides comprising amino acid sequences selected from SEQ ID NO: 21-377 and / or SEQ ID NO: 739-740.

[0061] In some embodiments, the polynucleotide encoding the polypeptide is a polynucleotide encoding an N-terminal cleavage, C-terminal cleavage, or fragment of an amino acid sequence selected from SEQ ID NO: 21-377 and / or SEQ ID NO: 739-740. The N-terminal cleavage, C-terminal cleavage, or fragment may contain, for example, at least 10, at least 12, at least 14, at least 16, at least 18, at least 20, at least 30, at least 40, at least 50, at least 75, at least 100, at least 200, at least 300, or at least 400 consecutive amino acids selected from SEQ ID NO: 21-377 and / or SEQ ID NO: 739-740.

[0062] In some embodiments, the polynucleotides of the present disclosure include steryl α-motif domain-containing protein 11, nephrocystin-4, espin, nicotinamide / nicotinic acid mononucleotide adenylyltransferase 1, mitofusin-2, ER membrane protein complex subunit 1, phospholipase A2 group V, dehydrodritil diphosphate synthase complex subunit, palmitoyl protein thioesterase 1, extra-long chain fatty acid elongation protein 1, and protein O-linked mannose β-1,2-N-acetylglucosaminyl Lansferase 1, retinoid isomerohydrolase, retina-specific phospholipid transport ATPase, collagen α-1(XI), guanine nucleotide-binding protein G(t) subunit α-2, chloride channel CLIC-like protein 1, DNA damage-modulating autophagy modulator protein 2, U4 / U6 nuclear small ribonucleoprotein Prp3, α-endosulfin, semaphorin-4A, cyclic AMP-dependent transcription factor ATF-6α, hemisentin-1, complement factor H, Crams protein homolog 1, adiponectin receptor Body protein 1, protein RD3, serine / threonine-protein kinase Nek2, feline leukemia virus subgroup C receptor-related protein 1, usherin, serologically defined colon cancer antigen 8, olfactory receptor 2W3, NBAS subunit of NRZ tethering factor complex, cytoplasmic carboxypeptidase-like protein 5, zinc finger protein 513, flagellar transport protein 172 homolog, photoreceptor ciliary actin regulator, EGF-containing fibrin-like extracellular matrix protein 1 / TLE family member 5, protein FAM161A, WD repeat-containing planar cell polarity effector protein Fritz homolog, centrosome-related protein ALMS1, U5 nuclear small ribonucleoprotein 200kDa helicase, metal transporter CNNM4, cyclic nucleotide gate cation channel α-3, nephrocystin-1, tyrosine-protein kinase Mer, Valday-Beedl syndrome 5 protein, ceramide kinase-like protein, neurogenic differentiation factor 1, transmembrane protein 237, inward rectifying potassium channel 13, S-arrestin, secreted phosphoprotein 24,CCA tRNA nucleotidyltransferase 1 (mitochondrial), sodium bicarbonate cotransporter 3, leucine zipper transcription factor-like protein 1, guanine nucleotide-binding protein G(t) subunit α-1, 3-prime repair exonuclease 1, MAP kinase-activated protein kinase 3, ataxin-7, vitamin K-dependent protein S, ADP ribosylation factor-like protein 6, photoreceptor matrix proteoglycan 2, IQ calmodulin-binding motif-containing protein 1, rhodopsin, nephrocystin-3, clarine-1, putative cationic amino acid transporter / solute carrier family 7 members 14, choline phosphate cytidylyltransferase A, 19kDa centrosome protein, rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit β, Wolfram Protein 1, homeobox protein HMX1, Ras-related protein Rab-28, coiled-coil C2 domain-containing protein 2A, prominin-1, adhesion-type G protein-coupled receptor A3, death domain-containing protein 1, WD repeat-containing protein 19, cGMP gate cation channel α-1, CDGSH iron-sulfur domain-containing protein 2, microsomal triglyceride transport protein large subunit, leucine-rich repeat, immunoglobulin-like domain / transmembrane domain-containing protein 3, Valday-Beedl syndrome protein 7, Valday-Beedl syndrome protein 12, major promoter superfamily domain-containing protein 8, serine / threonine-protein kinase PLK4, lecithin retinol acyltransferase, Toll-like receptor 3, cytochrome P450 4V2, Spliceosome-related protein CWC27 homolog, Centrosome protein POC5, Versican core protein, Adhesion-type G protein-coupled receptor V1, COUP transcription factor 1, Mitochondrial outer membrane protein SLC25A46, Catenin α-1, Histidine--tRNA ligase (cytoplasm), Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit α, Metabotropic glutamate receptor 6, Serine / threonine-protein kinase MAK, Complement C2, Complement factor B, Tubby-related protein 1, Guanylyl cyclase-activated protein 1, Guanylyl cyclase-activated protein 2, Peripherin-2,Photoreceptor matrix proteoglycan 1, iShat homolog protein, collagen α-1(IX) chain, regulatory synaptic membrane exocytosis protein 1, level cylin, very long chain fatty acid elongation protein 4, PR domain zinc finger protein 13, reticulon-4 interacting protein 1 (mitochondrial), jubelin, peroxisome targeting signal 2 receptor, CCR4-NOT transcription complex subunit 9, aromatic hydrocarbon receptor, Kelch-like protein 7, retinitis pigmentosa protein 9, protein PTHB 1, peroxisome ATPase PEX 1, tetraspanin-1 2, inosine-5'-monophosphate dehydrogenase 1, shortwave sensitive opsin 1, UPF0606 protein KIAA1549, retinitis pigmentosa-like protein 1, disintegrin / metalloproteinase domain-containing protein 9, heparan-α-glucosaminid N-acetyltransferase, oxygen regulatory protein 1, α-tocopherol transport protein, centrosome / spindle pole-related protein 1, dynamin-like 120kDa protein (mitochondrial), peroxisome formation factor 2, cyclic nucleotide gate cation channel β-3, ciliary / flagellar-related protein 418, growth / differentiation factor 6, regulatory synaptic membrane exocytosis protein 2, voltage-gated potassium channel superfamily V member 2, E3 ubiquitin protein ligase Topors, 78kDa centrosome protein, inversin, U4 / U6 nuclear small ribonucleotide protein Prp4, Warlin, E3 ubiquitin protein ligase TRIM32, Toll-like receptor 4, cytoplasmic dynein 2 intermediate chain 2, programmed cell death protein 2, exosome complex component RRP4, phosphatidylinositol polyphosphate 5-phosphatase type IV, phytanoyl-CoA dioxygenase (peroxisome), acyl-CoA binding domain-containing protein, protocadherin-15, retinol-binding protein 3, DNA excision repair protein ERCC-6, hexokinase-1, cadherin-23, cadherin-related family member 1, RPE retinal G protein-coupled receptor, kinesin-like protein KIF11, retinol-binding protein 4, cone cGMP-specific 3',5'-cyclic phosphodiesterase subunit α,Pairbox protein Pax-2, PDZ domain-containing protein 7, ADP-ribosylation factor-like protein 3, BBSome interacting protein 1, age-related macular degeneration-sensitive protein 2, serine protease HTRA1, ornithine aminotransferase (mitochondrial), zinc finger protein 408, Tubby protein homolog, transcription enhancer factor TEF-1, harmonin, transmembrane protein 216, bethroffin-1, isoaspartyl peptidase / L-asparaginase, rod extrasegmental membrane protein 1, bal Dae-Beedle syndrome protein 1, calcium-binding protein 4, low-density lipoprotein receptor-related protein 5, calpain-5, atypical myosin-VIIa, transmembrane protein 126A, frizzled-4, cytoplasmic dynein 2 light intermediate chain 1, 164kDa centrosome protein, complement C1q tumor necrosis factor-related protein 5, membrane frizzled-related protein, voltage-gated calcium channel subunit α-2 / δ-4, guanine nucleotide-binding protein G(I) / G(S) / G(T) subunit β-3, retinal cone rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit γ, collagen α-1(II) chain, matrix metalloproteinase-19, retinol dehydrogenase 5, T complex protein 1 subunit β, Balday-Beedl syndrome 10 protein, 290kDa centrosome protein, POC1 centriole protein homolog B, mevalonate kinase, flagellar transport protein 81 homolog, mitochondrial translation termination factor in rescue, intrinsic membrane protein 2B, retinoblastoma-associated protein, RCC1 and BTB domain-containing protein 1, rhodopsinkinase -ase GRK1, X-linked retinitis pigmentosa GTPase regulatory factor interacting protein 1, neuroretinal specific leucine zipper protein, homeobox protein OTX2, retinol dehydrogenase 11, retinol dehydrogenase 12, tubulin polyglutamylase TTLL5, spermatogenesis-related protein 7, tetratricopeptide repeat protein 8, fibrin-5, transient receptor potential cation channel subfamily M member 1, γ-tubulin complex component 4, sodium / potassium / calcium exchanger 1, photoreceptor-specific nuclear receptor,Valday-Beedl syndrome 4 protein, calcium and integrin-binding family member 2, retinaldehyde-binding protein 1, N-acetylglucosamine-1-phosphotransferase subunit γ, flagellar transport protein 140 homolog, clatherin-related protein 1, ATP-binding cassette subfamily member C 6, ketimine reductase μ-crystallin, battenin, zinc finger protein 423, protein phantom, Valday-Beedl syndrome 2 protein, ADP-ribosylation factor-like protein 2-binding protein, cyclic nucleotide gate cation channel β-1, cadherin-3, premRNA splicing factor ATP-dependent RNA he Licase PRP16, A disintegrin metalloproteinase with thrombospondin motif 18, solute carrier family 38 member 8, retinal guanylyl cyclase 1, premRNA processing splicing factor 8, aromatic hydrocarbon interacting protein-like 1, membrane-bound phosphatidylinositol transport protein 3, protein unc-119 homolog A, putative G protein-coupled receptor 179, tectonic-like complex member MKS1, carbonic anhydrase 4, G protein signaling regulator 9, aryl sulfatase G, premRNA splicing regulator USH1G, photoreceptor disk component PRCD, phascin-2, retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit γ, laminin subunit α-1, AFG3-like protein 2, cone-rod homeobox protein, receptor expression-enhancing protein 6, anterior retinal nerve fold homeobox protein 2, complement C3, Rho guanine nucleotide exchange factor 18, patatin-like phospholipase domain-containing protein 6, G protein signaling regulator 9 binding protein, optic nerve atrophy 3 protein, U4 / U6 nuclear small ribonucleoprotein Prp31, isocitrate dehydrogenase [NAD] subunit β (mitochondria), pantothenate kinase 2 (mitochondria), protein jagged-1, molecular chaperone MKKS, centrosome protein Kizuna, lysophosphatidylserine lipase ABHD12, kinesin-like protein KIF3B, centrosome-related protein CEP250, premRNA processing factor 6,Cilia / flagellar-related protein 410, dynamin-1-like protein, metalloproteinase inhibitor 3, flagellar transport protein 27 homolog, fibrin-1, MIEF1 upstream open reading frame protein, aconitate hydratase (mitochondria), γ-tubulin complex component 6, centrioles / centroneal satellite proteins, retinosuxin, protein XRP2, dystrophin, X-linked retinitis pigmentosa GTPase regulator, nictaropine, Xaa-prodipeptidase, noline, voltage-gated L-type calcium channel subunit α-1F, phosphoglycerate kinase 1, Rab protein geranylgeranyltransferase component A1, mitochondrial import inner membrane transport enzyme subunit Tim8 A, ribose phosphate pyrophosphokinase 1, long-wave sensitive opsin 1, medium-wave sensitive opsin 1, short-wave sensitive opsin 1, transcription factor A (mitochondria), NADH ubiquinone oxidoreductase chain 1, NADH ubiquinone oxidoreductase chain 2, NADH ubiquinone oxidoreductase chain 3, NADH ubiquinone oxidoreductase chain 4L, NADH ubiquinone oxidoreductase chain 4, NADH ubiquinone oxidoreductase chain 5, NADH ubiquinone oxidoreductase chain 6, ATP synthase subunit a, ATP synthase protein 8, cytochrome c oxidase subunit 1, cytochrome c oxidase subunit 3, cytochrome b, leucine-tRNA ligase (mitochondria), indiscriminate glutamyl-tRNA synthesizer, Tase EARS2 (mitochondrial), lysine--tRNA ligase, histidine--tRNA ligase (mitochondrial), serine--tRNA ligase (mitochondrial), putative proline--tRNA ligase (mitochondrial), cyanocobalamin reductase / alkylcobalamin dealkylase, POU domain, class 3, transcription factor 4, ribosomal protein S6 kinase α-6, ciliation and planar polarity effector 1, Meckelin, TRAF3 interaction protein 1, flagellar transport protein 74 homolog, vesicles S-phase cyclin A-related protein, sodium channel and clathrin linker 1, protein TALPID3, tectonic-2, ADP-ribosylation factor-like protein 13B, B9 domain-containing protein 1, B9 domain-containing protein 2, C2 domain-containing protein 3, 41kDa centrosome protein, 104kDa centrosome protein, 120kDa centrosome protein, flagellar transport protein 172 homolog, katanin-interacting protein, kinesin-like protein KIF7, retinal rod rhodopsin-sensitive cGMP Encodes any one or more of the following in any preferred combination: 3',5'-cyclic phosphodiesterase subunit δ, tectonic-1, tectonic-3, transmembrane protein 107, transmembrane protein 138, transmembrane protein 231, tetratricopeptide repeat protein 21B, nuclear receptor ROR-α, β nerve growth factor, collagen α-2(VIII) chain, solute carrier family 4 member 11, zinc finger E-box linked homeobox 1, keratin type II cuticle Hb3, keratin type I cytoskeleton 12, transforming growth factor-β-inducing protein ig-h3, tumor-associated calcium signaling factor 2, carbohydrate sulfotransferase 6, gelzolin, UbiA prenyltransferase domain-containing protein 1, decorin, 1-phosphatidylinositol 3-phosphate 5-kinase, transcription factor Ovo-like 2, Gleinihead-like protein 2 homolog, and / or any chimeric polypeptides thereof.

[0063] The polynucleotides of this disclosure encoding polypeptides may further encode additional coding and non-coding sequences. Examples of additional coding and non-coding sequences may include, but are not limited to, sequences encoding additional polypeptide tags (e.g., encoded in-frame with polypeptides to produce fusion proteins), introns (e.g., native, modified, or heterologous introns), 5' and / or 3'UTRs (e.g., native, modified, or heterologous 5' and / or 3'UTRs), etc. Examples of preferred polypeptide tags may include, but are not limited to, any combination of purified tags, e.g., hist tags, flag tags, maltose-binding protein and glutathione-S-transferase tags, detection tags, e.g., photometrically measurable tags (e.g., green fluorescent protein, red fluorescent protein, etc.), tags having detectable enzymatic activity (e.g., alkaline phosphatase, etc.), secretion sequences, signal sequences, reader sequences and / or stabilization sequences, tags containing protease cleavage sites (e.g., furin cleavage sites, TEV cleavage sites, thrombin cleavage sites, etc.). In some embodiments, the 5' and / or 3'UTR increases the stability, localization, and / or translation efficiency of polynucleotides. In some embodiments, the 5' and / or 3'UTR improves the level and / or duration of protein expression. In some embodiments, the 5' and / or 3'UTR includes elements (e.g., one or more miRNA binding sites) that can block or reduce off-target expression (e.g., inhibiting expression in a particular cell type (e.g., nerve cells), at a particular time in the cell cycle, at a particular developmental stage, etc.). In some embodiments, the 5' and / or 3'UTR includes elements (e.g., one or more miRNA binding sites) that can enhance the expression of encoded polypeptides in a particular cell type.

[0064] In some embodiments, the polynucleotides of the present disclosure encoding a polypeptide are functionally linked to one or more (e.g., one or more, two or more, three or more, four or more, five or more, ten or more, etc.) regulatory sequences. The term “regulatory sequence” may include enhancers, insulators, promoters, and other expression regulatory elements (e.g., polyadenylation signals). Any suitable enhancers known in the art may be used, including, for example, enhancer sequences derived from mammalian genes (e.g., globin, elastase, albumin, α-fetoprotein, insulin, etc.), enhancer sequences derived from eukaryotic viruses (e.g., SV40 enhancers (bp 100-270) on the latter half of the origin of replication, cytomegalovirus early promoter enhancers, polyoma enhancers on the latter half of the origin of replication, adenovirus enhancers, etc.), and any combination thereof. For example, any suitable insulator known in the art may be used, including HSV chromatin boundary (CTRL / CTCF binding / insulator) elements CTRL1 and / or CTRL2, chicken high-sensitivity site 4 insulator (cHS4), human HNRPA2B1-CBX3 ubiquita chromatin opening element (UCOE), human interferon-β gene (IFNB1) derived scaffold / matrix attachment region (S / MAR), and any combination thereof.For example, any suitable promoter known in the art (e.g., suitable for transcription in mammalian host cells), including promoters obtained from the genomes of viruses (e.g., polyomavirus, fowlpox virus, adenovirus (adenovirus 2, etc.), bovine papillomavirus, aerosarcoma virus, cytomegalovirus, retrovirus, hepatitis B virus, Simian virus 40 (SV40), etc.), promoters derived from heterologous mammalian genes (e.g., actin promoter (e.g., β-actin promoter), ubiquitin promoter (e.g., ubiquitin C (UbC) promoter), phosphoglycerate kinase (PGK) promoter, immunoglobulin promoter, heat shock promoter, etc.), promoters derived from homologous mammalian genes, synthetic promoters (e.g., CAG promoter), and any combination thereof, may be used, provided they are compatible with the host cell. Regulatory sequences may include those that instruct the constitutive expression of nucleic acids, as well as tissue-specific regulatory sequences and / or inducible or repressive sequences.

[0065] In some embodiments, the polynucleotides of the Disclosure are functionally ligated to one or more heterologous promoters. In some embodiments, one or more heterologous promoters are one or more of constitutive promoters, tissue-specific promoters, temporal promoters, spatial promoters, inductive promoters, and repressive promoters. In some embodiments, one or more heterologous promoters are one or more of the human cytomegalovirus (HCMV) pre-early promoter, human elongation factor-1 (EF1) promoter, human β-actin promoter, human UbC promoter, human PGK promoter, synthetic CAGG promoter, and any combination thereof. In some embodiments, the polynucleotides of the Disclosure encoding a polypeptide are functionally ligated to an HCMV promoter.

[0066] In some embodiments, a polynucleotide of the Disclosure encoding a polypeptide expresses the polypeptide when the polynucleotide is delivered to one or more target cells of the subject (e.g., one or more cells such as the eye, anterior chamber, posterior chamber, ciliary body, corneal epithelial cells, rod cells, cone cells, photoreceptors, retinal pigment epithelial cells, retinal ganglion cells, bipolar cells, horizontal cells, Müller cells, axonless cells, etc.). In some embodiments, polypeptide expression enhances, increases, strengthens and / or supplements the level, function and / or activity of the polypeptide in one or more target cells of the subject (e.g., compared to before polypeptide expression, compared to the level of endogenous polypeptide expressed in the cells). In some embodiments, polypeptide expression provides prophylactic, mitigating, or therapeutic relief of one or more signs or symptoms of an eye condition or disease in the subject (e.g., compared to before polypeptide expression).

[0067] Chimeric polypeptide In some embodiments, the polynucleotides of this disclosure encode a chimeric polypeptide comprising a first polypeptide and a second polypeptide. In some embodiments, the first and second polypeptides are the same. In some embodiments, the first and second polypeptides are different. In some embodiments, the chimeric polypeptide further comprises a linker polypeptide that links the first and second polypeptides. In some embodiments, the chimeric polypeptide comprises, from n-terminus to c-terminus, first polypeptide-linker polypeptide-second polypeptide. The first and / or second polypeptide may be any polypeptide described herein or known in the art.

[0068] In some embodiments, the linker polypeptide is a cleavable linker polypeptide. Any cleavable linker polypeptide known in the art, such as T2A linkers, P2A linkers, E2A linkers, and F2A linkers, can be used in the chimeric polypeptide of this disclosure. In some embodiments, the linker polypeptide is a T2A linker polypeptide. An exemplary nucleic acid sequence encoding a T2A linker polypeptide is provided as SEQ ID NO:1. An exemplary amino acid sequence of a T2A linker polypeptide is provided as SEQ ID NO:5. In some embodiments, the linker polypeptide is a P2A linker polypeptide. An exemplary nucleic acid sequence encoding a P2A linker polypeptide is provided as SEQ ID NO:2. An exemplary amino acid sequence of a P2A linker polypeptide is provided as SEQ ID NO:6. In some embodiments, the linker polypeptide is an E2A linker polypeptide. An exemplary nucleic acid sequence encoding an E2A linker polypeptide is provided as SEQ ID NO:3. An exemplary amino acid sequence of an E2A linker polypeptide is provided as SEQ ID NO:7. In some embodiments, the linker polypeptide is an F2A linker polypeptide. An exemplary nucleic acid sequence encoding an F2A linker polypeptide is provided as SEQ ID NO:4. An exemplary amino acid sequence of an F2A linker polypeptide is provided as SEQ ID NO:8. In some embodiments, the linker polypeptide comprises a sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with an amino acid sequence selected from SEQ ID NO:68-71. In some embodiments, the linker polypeptide comprises a sequence selected from SEQ ID NO:5-8.

[0069] In some embodiments, the linker polypeptide is a non-cleavable linker polypeptide. For example, Any non-cleavable linker polypeptide known in the art, including TIFF2026515744000002.tif46167, may be used in the chimeric polypeptide of this disclosure. In some embodiments, the linker polypeptide comprises a sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with an amino acid sequence selected from SEQ ID NO:9-20. In some embodiments, the linker polypeptide comprises a sequence selected from SEQ ID NO:9-20.

[0070] In some embodiments, the polynucleotides of the Disclosure do not contain a coding sequence for collagen α-1(VII) chain polypeptide (COL7) (e.g., a transgene encoding said polypeptide). In some embodiments, the polynucleotides of the Disclosure do not contain a coding sequence for lysyl hydroxylase 3 polypeptide (LH3) (e.g., a transgene encoding said polypeptide). In some embodiments, the polynucleotides of the Disclosure do not contain a coding sequence for keratin type I cytoskeleton 17 polypeptide (KRT17) (e.g., a transgene encoding said polypeptide). In some embodiments, the polynucleotides of the Disclosure do not contain a coding sequence for transglutaminase (TGM) polypeptide (e.g., human transglutaminase polypeptide, e.g., human TGM1 polypeptide and / or human TGM5 polypeptide) (e.g., a transgene encoding said polypeptide). In some embodiments, the polynucleotides of the Disclosure do not contain coding sequences (e.g., transgenes encoding such proteins) of cosmetic proteins (e.g., collagen proteins, fibronectin, elastin, lumican, vitronectin / vitronectin receptors, laminin, neuromodulators, fibrillin, and further extracellular cutaneous matrix proteins). In some embodiments, the polynucleotides of the Disclosure do not contain coding sequences (e.g., transgenes encoding such antibodies) of antibodies (e.g., full-length antibodies, antibody fragments, etc.). In some embodiments, the polynucleotides of the Disclosure do not contain coding sequences (e.g., transgenes encoding such antibodies) of serine protease inhibitor Kazal-type (SPINK) polypeptides (e.g., human SPINK polypeptides such as SPINK5 polypeptide). In some embodiments, the polynucleotides of the Disclosure do not contain coding sequences (e.g., transgenes encoding such polypeptides) of filaggrin or filaggrin 2 polypeptides (e.g., human filaggrin or filaggrin 2 polypeptide). In some embodiments, the polynucleotides of the present disclosure do not contain a coding sequence (e.g., a transgene encoding the cystic fibrosis membrane conductance regulator (CFTR) polypeptide (e.g., a human CFTR polypeptide). In some embodiments,The polynucleotides of this disclosure are ichthyosis-related polypeptides (e.g., ATP-binding cassette subfamily A member 12 polypeptide, 1-acylglycerol-3-phosphate O-acyltransferase ABHD5 polypeptide, aldehyde dehydrogenase family 3 member A2 polypeptide, arachidonic acid 12-lipoxygenase 12R polypeptide, hydroperoxide isomerase ALOXE3 polypeptide, AP-1 complex subunit σ-1A polypeptide, arylsulfatase E polypeptide, caspase-14 polypeptide, corneodesmosine polypeptide, ceramide synthase 3 polypeptide, carbohydrate sulfotransferase 8 polypeptide, claudin-1 polypeptide, cystatin-A polypeptide, cytochrome P450) 4F22 polypeptide, 3-β-hydroxysteroid-δ(8),δ(7)-isomerase polypeptide, extra-long chain fatty acid elongation protein 4 polypeptide, filaggrin polypeptide, filaggrin 2 polypeptide, Gap-linked β-2 polypeptide, Gap-linked β-3 polypeptide, Gap-linked β-4 polypeptide, Gap-linked β-6 polypeptide, 3-ketodihydrosphingosine reductase polypeptide, keratin type II cytoskeleton 1 polypeptide, keratin type II cytoskeleton 2 epithelial polypeptide, keratin type I cytoskeleton 9 polypeptide, keratin type I cytoskeleton 10 polypeptide, lipase member N polypeptide, loricrin polypeptide, membrane-bound transcription factor site-2 protease polypeptide, magnesium transporter NIPA4 polypeptide, sterol-4-α-carboxylic acid 3-dehydrogenase, decarboxylation polypeptide, peroxisome targeting signal 2 receptor polypeptide, D-3-phosphoglycerate dehydrogenase polypeptide, phytanoyl-CoA dioxygenase, peroxisome polypeptide, patatin-like phospholipase domain-containing protein 1 polypeptide, proteasome maturation protein polypeptide, phosphoserine aminotransferase polypeptide, short-chain dehydrogenase / reductase family 9C member 7 polypeptides, serpine B 8 polypeptide, long-chain fatty acid transport protein 4 polypeptides, synaptosome-related protein 29 polypeptides,The polynucleotides of the present disclosure do not contain coding sequences (e.g., transgenes encoding such polypeptides) of tumorigenicity suppressor 14 protein polypeptide, steryl sulfatase polypeptide, vacuolar protein sorting-related protein 33B polypeptide, and CAAX prenyl protease 1 homolog polypeptide. In some embodiments, the polynucleotides of the present disclosure do not contain coding sequences (e.g., transgenes encoding such polypeptides) of collagen α-1(VII) chain polypeptide, lysyl hydroxylase 3 polypeptide, keratin type I cytoskeleton 17 polypeptide, and / or any chimeric polypeptides thereof. In some embodiments, the polynucleotides of this disclosure include collagen α-1(VII) chain polypeptide, lysyl hydroxylase 3 polypeptide, keratin type I cytoskeleton 17 polypeptide, transglutaminase (TGM) polypeptide, filaggrin polypeptide, beauty protein, antibody, SPINK polypeptide, CFTR polypeptide, ichthyosis-related polypeptide, α-1-antitrypsin polypeptide, sodium-dependent phosphate transport protein 2B polypeptide, dynein heavy chain 5 axonele polypeptide, dynein heavy chain 11 axonele polypeptide, coiled-coil domain-containing protein 39 polypeptide, dynein intermediate chain 1 axonele polypeptide, coiled-coil domain-containing protein 40 polypeptide, coiled-coil domain-containing protein 103 polypeptide, sperm-related antigen 1 polynucleotide Peptides, 10 polypeptides containing zinc finger MYND domain, 4 polypeptides containing armadillo repeats, 151 polypeptides containing coiled-coil domains, dynein intermediate chain biaxial polypeptide, radial spokehead 1 homolog polypeptide, 114 polypeptides containing coiled-coil domains, radial spokehead 4 homolog A polypeptide, dynein assembly factor 1axial polypeptide, dynein assembly factor biaxial polypeptide, 6 polypeptides containing leucine-rich repeats, pulmonary surfactant-related protein B polypeptide, pulmonary surfactant-related protein C polypeptide, homeobox protein Nkx-2.1 polypeptide, 3 polypeptides belonging to ATP-binding cassette subfamily A member.Cytokine receptor common subunit β polypeptide, granulocyte-macrophage colony-stimulating factor receptor subunit α polypeptide, bone morphogenetic protein receptor type 2 polypeptide, sarplasmosis / endoplasmic reticulum calcium ATPase 2 polypeptide, serine / threonine-protein kinase receptor R3 polypeptide, endoglin polypeptide, decapentaprezic and mothers against It does not contain coding sequences (e.g., transgenes encoding such polypeptides) for any of the following: decapentaplegic homolog 9 polypeptide, caveolin-1 polypeptide, potassium channel subfamily K member 3 polypeptide, eIF-2-α kinase GCN2 polypeptide, lung surfactant-associated protein A2 polypeptide, telomerase reverse transcriptase polypeptide, diskelin polypeptide, telomere elongation helicase 1 regulator polypeptide, poly(A)-specific ribonuclease PARN polypeptide, TERF1 interacting nuclear factor 2 polypeptide, H / ACA ribonucleoprotein complex noncore subunit NAF1 polypeptide, mucin-5B polypeptide, desmoplakin polypeptide, CST complex subunit STN1 polypeptide, dipeptidyl peptidase 9 polypeptide, and / or any of these chimeric polypeptides.

[0071] In some embodiments, the polynucleotides of the Disclosure do not contain coding sequences for immunomodulatory polypeptides (e.g., transgenes encoding such polypeptides). In some embodiments, the polynucleotides of the Disclosure do not contain coding sequences for cytokine polypeptides and / or chemokine polypeptides (e.g., transgenes encoding such polypeptides). In some embodiments, the polynucleotides of the Disclosure do not contain coding sequences for cytokine polypeptides (e.g., transgenes encoding such polypeptides). In some embodiments, the polynucleotides of the Disclosure do not contain coding sequences for IL-1 polypeptide, IL-2 polypeptide, IL-7 polypeptide, IL-12 polypeptide, IL-13 polypeptide, IL-15 polypeptide, IL-17 polypeptide, IL-18 polypeptide, IL-28 polypeptide, IL-32 polypeptide, IL-33 polypeptide, IL-34 polypeptide, TNFα polypeptide, IFNγ polypeptide, G-CSF polypeptide, GM-CSF polypeptide, and / or any chimeric polypeptide thereof (e.g., transgenes encoding such polypeptides).

[0072] In some embodiments, the polynucleotides of the Disclosure do not contain coding sequences for chemokine polypeptides (e.g., transgenes encoding such polypeptides). In some embodiments, the polynucleotides of the Disclosure do not contain coding sequences for CXCL1 polypeptide, CXCL2 polypeptide, CXCL8 polypeptide, CXCL9 polypeptide, CXCL11 polypeptide, CXCL16 polypeptide, CCL2 polypeptide, CCL3 polypeptide, CCL4 polypeptide, CCL5 polypeptide, CCL11 polypeptide, and / or any chimeric polypeptide thereof (e.g., transgenes encoding such polypeptides).

[0073] Recombinant nucleic acids In some embodiments, this disclosure relates to recombinant nucleic acids comprising one or more of the polynucleotides described herein. In some embodiments, the recombinant nucleic acid is a vector (e.g., an expression vector, a display vector, etc.). In some embodiments, the vector is a DNA vector or an RNA vector. Generally, a vector suitable for maintaining, amplifying, and / or expressing polynucleotides to produce one or more polypeptides in a subject may be used. Examples of suitable vectors may include, for example, plasmids, cosmids, episomes, transposons, and viral vectors (e.g., adenovirus vectors, adeno-associated virus vectors, vaccinia virus vectors, Sindbisvirus vectors, measles vectors, herpesvirus vectors, lentivirus vectors, retrovirus vectors, etc.). In some embodiments, the vector is a herpesvirus vector. In some embodiments, the vector is capable of autonomous replication in host cells. In some embodiments, the vector is not capable of autonomous replication in host cells. In some embodiments, the vector can be incorporated into host DNA. In some embodiments, the vector cannot be incorporated into host DNA (e.g., it is episomal). Methods for preparing vectors containing one or more polynucleotides of interest are well known to those skilled in the art, including, for example, by synthetic chemistry or by artificial manipulation of isolated nucleic acid segments (e.g., by genetic engineering techniques).

[0074] In some embodiments, the recombinant nucleic acids of this disclosure are herpes simplex virus (HSV) amplicons. Herpes virus amplicons, including their structural features and methods for producing them, are generally known to those skilled in the art (see, for example, de Silva S. and Bowers W. “Herpes Virus Amplicon Vectors”. Viruses 2009, 1, 594-629). In some embodiments, the herpes simplex virus amplicon is an HSV-1 amplicon. In some embodiments, the herpes simplex virus amplicon is an HSV-1 hybrid amplicon. Examples of HSV-1 hybrid amplicons may include, but are not limited to, HSV / AAV hybrid amplicons, HSV / EBV hybrid amplicons, HSV / EBV / RV hybrid amplicons, and / or HSV / Sleeping Beauty hybrid amplicons. In some embodiments, the amplicon is an HSV / AAV hybrid amplicon. In some embodiments, the amplicon is an HSV / Sleeping Beauty hybrid amplicon.

[0075] In some embodiments, the recombinant nucleic acids of the Disclosure are recombinant herpesvirus genomes. Recombinant herpesvirus genomes may be recombinant genomes derived from any member of the Herpesviridae family of DNA viruses known in the Art, including, for example, recombinant herpes simplex virus genomes, recombinant varicella-zoster virus genomes, recombinant human cytomegalovirus genomes, recombinant herpesvirus 6A genomes, recombinant herpesvirus 6B genomes, recombinant herpesvirus 7 genomes, recombinant Epstein-Barr virus genomes, recombinant Kaposi's sarcoma-associated herpesvirus genomes, and any combination or derivatives thereof. In some embodiments, recombinant herpesvirus genomes include one or more (e.g., one or more, two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, etc.) inactivating mutations. As used herein, “inactivating mutation” may mean any mutation that results in a reduced, undetectable, or removed amount and / or function of a gene or regulon product (RNA or protein) (e.g., compared to a corresponding sequence lacking the inactivating mutation). Examples of inactivating mutations may include, but are not limited to, deletions, insertions, point mutations, and rearrangements in transcriptional regulatory sequences (promoters, enhancers, insulators, etc.) and / or coding sequences of a given gene or regulon. Any suitable method known in the art to measure the amount of a gene or regulon product may be used, for example, qPCR, Northern blotting, RNA-seq, Western blotting, ELISA, etc. In some embodiments, one or more inactivating mutations are in one or more (e.g., one or more, two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, etc.) herpesvirus genes. In some embodiments, the recombinant herpesvirus genome is attenuated (e.g., compared to the corresponding wild-type herpesvirus genome). In some embodiments, the recombinant herpesvirus genome is replication-capable. In some embodiments, the recombinant herpesvirus genome is replication-deficient.In some embodiments, recombinant herpesvirus genomes are not oncolytic.

[0076] In some embodiments, the recombinant nucleic acid is a recombinant herpes simplex virus (HSV) genome. In some embodiments, the recombinant herpes simplex virus genome contains one or more (e.g., one or more, two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, etc.) inactivating mutations. In some embodiments, one or more inactivating mutations are present in one or more (e.g., one or more, two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, etc.) herpes simplex virus genes. In some embodiments, the recombinant herpes simplex virus genome is attenuated (e.g., compared to the corresponding wild-type herpes simplex virus genome). In some embodiments, the recombinant herpes simplex virus genome is reproducible. In some embodiments, the recombinant herpes simplex virus genome is replication-deficient. In some embodiments, the recombinant herpes simplex virus genome is not oncolytic.

[0077] In some embodiments, the recombinant herpesvirus genome is a recombinant herpes simplex virus type 1 (HSV-1) genome, a recombinant herpes simplex virus type 2 (HSV-2) genome, or any derivative thereof. In some embodiments, the recombinant herpes simplex virus genome is a recombinant HSV-1 genome. In some embodiments, the recombinant HSV-1 genome is, for example, 17, Ty25, R62, S25, Ku86, S23, R11, Ty148, Ku47, H166 syn, 1319-2005, F-13, M-12, 90237, F-17, KOS, 3083-2008, F12g, L2, CD38, H193, M-15, India 2011, 0116209, F-11I, 66-207, 2762, 369-2007, 3355, MacIntyre, McKrae, 7862, 7-h se, HF10, 1394,2005, 270-2007, OD4, SC16, M-19, 4J1037, 5J1060, J1060, KOS79, 132- It may be derived from any HSV-1 strain known in the art, including 1988, 160-1982, H166, 2158-2007, RE, 78326, F18g, F11, 172-2010, H129, F, E4, CJ994, F14g, E03, E22, E10, E06, E11, E25, E23, E35, E15, E07, E12, E14, E08, E19, E13, ATCC 2011 strain, etc. (see, for example, Bowen et al. J Virol. 2019 Apr 3;93(8)). In some embodiments, the recombinant HSV-1 genome is derived from the KOS strain. In some embodiments, the recombinant HSV-1 genome is not derived from the McKrae strain. In some embodiments, recombinant HSV-1 genomes are attenuated (e.g., compared to the corresponding wild-type HSV-1 genome). In some embodiments, recombinant HSV-1 genomes are replication-capable. In some embodiments, recombinant HSV-1 genomes are replication-deficient. In some embodiments, recombinant HSV-1 genomes are not oncolytic.

[0078] In some embodiments, the recombinant herpes simplex virus genome contains inactivating mutations in at least one, at least two, at least three, at least four, at least five, at least six, at least seven, or all eight of the following herpes simplex virus genes: Infectious Cell Protein (or Infectious Cell Polypeptide) (ICP)0, ICP4, ICP22, ICP27, ICP47, Thymidine Kinase (tk), Long Unique Region (UL)41, and / or UL55. In some embodiments, the recombinant herpes simplex virus genome does not contain inactivating mutations in ICP34.5 (one or both copies) and / or ICP47 herpes simplex virus gene (e.g., to avoid the production of immunostimulatory virus). In some embodiments, the recombinant herpes simplex virus genome does not contain inactivating mutations in ICP34.5 (one or both copies) herpes simplex virus gene. In some embodiments, the recombinant herpes simplex virus genome does not contain inactivating mutations in ICP47 herpes simplex virus gene. In some embodiments, the recombinant herpes simplex virus genome does not contain inactivating mutations in the ICP34.5 (one or both copies) and ICP47 herpes simplex virus genes. In some embodiments, the recombinant herpes simplex virus genome is not oncolytic. In some embodiments, the recombinant herpes simplex virus genome is conditionally non-replicating. In some embodiments, the recombinant herpes simplex virus genome is conditionally non-replicating in cancerous cells.

[0079] In some embodiments, the recombinant herpes simplex virus genome contains an inactivating mutation in one or both copies of the ICP0 gene. In some embodiments, the recombinant herpes simplex virus genome contains an inactivating mutation in one or both copies of the ICP0 gene, and further contains inactivating mutations in one or both copies of the ICP4, ICP22, ICP27, ICP47, UL41, and / or UL55 genes. In some embodiments, the recombinant herpes simplex virus genome contains an inactivating mutation in one or both copies of the ICP0 gene and an inactivating mutation in one or both copies of the ICP4 gene. In some embodiments, the recombinant herpes simplex virus genome contains an inactivating mutation in one or both copies of the ICP0 gene and an inactivating mutation in the ICP22 gene. In some embodiments, the recombinant herpes simplex virus genome contains an inactivating mutation in one or both copies of the ICP0 gene and an inactivating mutation in the UL41 gene. In some embodiments, the recombinant herpes simplex virus genome includes an inactivating mutation in one or both copies of the ICP0 gene, an inactivating mutation in one or both copies of the ICP4 gene, and an inactivating mutation in the ICP22 gene. In some embodiments, the recombinant herpes simplex virus genome includes an inactivating mutation in one or both copies of the ICP0 gene, an inactivating mutation in one or both copies of the ICP4 gene, and an inactivating mutation in the UL41 gene. In some embodiments, the recombinant herpes simplex virus genome includes an inactivating mutation in one or both copies of the ICP0 gene, an inactivating mutation in the ICP22 gene, and an inactivating mutation in the UL41 gene. In some embodiments, the recombinant herpes simplex virus genome includes an inactivating mutation in one or both copies of the ICP0 gene, an inactivating mutation in one or both copies of the ICP4 gene, an inactivating mutation in the ICP22 gene, and an inactivating mutation in the UL41 gene. In some embodiments, the inactivating mutation is a deletion of the coding sequence in the ICP0 (one or both copies), ICP4 (one or both copies), ICP22, and / or UL41 gene.In some embodiments, the recombinant herpes simplex virus genome further includes inactivating mutations in the ICP27, ICP47, and / or UL55 genes.

[0080] In some embodiments, the recombinant herpes simplex virus genome contains an inactivating mutation in one or both copies of the ICP4 gene. In some embodiments, the recombinant herpes simplex virus genome contains an inactivating mutation in one or both copies of the ICP4 gene, and further contains inactivating mutations in one or both copies of the ICP0, ICP22, ICP27, ICP47, UL41, and / or UL55 genes. In some embodiments, the recombinant herpes simplex virus genome contains an inactivating mutation in one or both copies of the ICP4 gene and an inactivating mutation in the ICP22 gene. In some embodiments, the recombinant herpes simplex virus genome contains an inactivating mutation in one or both copies of the ICP4 gene and an inactivating mutation in the UL41 gene. In some embodiments, the recombinant herpes simplex virus genome contains an inactivating mutation in one or both copies of the ICP4 gene, an inactivating mutation in the ICP22 gene, and an inactivating mutation in the UL41 gene. In some embodiments, the inactivating mutation is a deletion in the coding sequence of the ICP4 (one or both copies), ICP22, and / or UL41 gene. In some embodiments, the recombinant herpes simplex virus genome further includes inactivating mutations in the ICP0 (one or both copies), ICP27, ICP47, and / or UL55 gene.

[0081] In some embodiments, the recombinant herpes simplex virus genome contains an inactivating mutation in the ICP22 gene. In some embodiments, the recombinant herpes simplex virus genome contains an inactivating mutation in the ICP22 gene and further contains inactivating mutations in the ICP0 (one or both copies), ICP4 (one or both copies), ICP27, ICP47, UL41, and / or UL55 genes. In some embodiments, the recombinant herpes simplex virus genome contains an inactivating mutation in the ICP22 gene and an inactivating mutation in the UL41 gene. In some embodiments, the inactivating mutation is a deletion in the coding sequence of the ICP22 and / or UL41 genes. In some embodiments, the recombinant herpes simplex virus genome further contains inactivating mutations in the ICP0 (one or both copies), ICP4 (one or both copies), ICP27, ICP47, and / or UL55 genes.

[0082] In some embodiments, the recombinant herpes simplex virus genome contains an inactivating mutation in the ICP27 gene. In some embodiments, the recombinant herpes simplex virus genome contains an inactivating mutation in the ICP27 gene and further contains inactivating mutations in the ICP0 (one or both copies), ICP4 (one or both copies), ICP22, ICP47, UL41, and / or UL55 genes. In some embodiments, the inactivating mutation is a deletion in the coding sequence of the ICP27 gene.

[0083] In some embodiments, the recombinant herpes simplex virus genome contains an inactivating mutation in the ICP47 gene. In some embodiments, the recombinant herpes simplex virus genome contains an inactivating mutation in the ICP47 gene and further contains inactivating mutations in the ICP0 (one or both copies), ICP4 (one or both copies), ICP22, ICP27, UL41, and / or UL55 genes. In some embodiments, the inactivating mutation is a deletion in the coding sequence of the ICP47 gene.

[0084] In some embodiments, the recombinant herpes simplex virus genome contains an inactivating mutation in the UL41 gene. In some embodiments, the recombinant herpes simplex virus genome contains an inactivating mutation in the UL41 gene and further contains inactivating mutations in the ICP0 (one or both copies), ICP4 (one or both copies), ICP22, ICP27, ICP47, and / or UL55 genes. In some embodiments, the inactivating mutation is a deletion in the coding sequence of the UL41 gene.

[0085] In some embodiments, the recombinant herpes simplex virus genome contains an inactivating mutation in the UL55 gene. In some embodiments, the recombinant herpes simplex virus genome contains an inactivating mutation in the UL55 gene and further contains inactivating mutations in the ICP0 (one or both copies), ICP4 (one or both copies), ICP22, ICP27, ICP47, and / or UL41 genes. In some embodiments, the inactivating mutation is a deletion in the coding sequence of the UL55 gene.

[0086] In some embodiments, the recombinant herpes simplex virus genome has internal repeat longs (IRs). L ) and internal repeat short (IR SThe recombinant herpes simplex virus genome contains an inactivating mutation (e.g., deletion of the region) in an internal repeat (joint) region. In some embodiments, inactivation (e.g., deletion) of the joint region removes one copy each of the ICP4 and ICP0 genes. In some embodiments, inactivation (e.g., deletion) of the joint region further inactivates (e.g., deletes) the promoters of the ICP22 and ICP47 genes. If desired, the expression of one or both of these genes can be restored by inserting a pre-early promoter into the recombinant herpes simplex virus genome (see, e.g., Hill et al. (1995). Nature 375 (6530): 411-415; Goldsmith et al. (1998). J Exp Med 187(3): 341-348). While we do not wish to be constrained by theory, it is thought that inactivating (e.g., deleting) the joint region may contribute to the stability of the recombinant herpes simplex virus genome and / or allow the recombinant herpes simplex virus genome to accommodate more and / or larger transgenes.

[0087] In some embodiments, the recombinant herpes simplex virus genome contains inactivating mutations in the ICP4 (one or both copies), ICP22, and ICP27 genes. In some embodiments, the recombinant herpes simplex virus genome contains inactivating mutations in the ICP4 (one or both copies), ICP27, and UL55 genes. In some embodiments, the recombinant herpes simplex virus genome contains inactivating mutations in the ICP4 (one or both copies), ICP22, ICP27, ICP47, and UL55 genes. In some embodiments, the inactivating mutations in the ICP4 (one or both copies), ICP27, and / or UL55 genes are deletions of the coding sequences in the ICP4 (one or both copies), ICP27, and / or UL55 genes. In some embodiments, inactivating mutations in the ICP22 and ICP47 genes are deletions in the promoter regions of the ICP22 and ICP47 genes (e.g., the ICP22 and ICP47 coding sequences are intact but not transcriptionally active). In some embodiments, the recombinant herpes simplex virus genome contains deletions in the coding sequences of the ICP4 (one or both copies), ICP27, and UL55 genes, and deletions in the promoter regions of the ICP22 and ICP47 genes. In some embodiments, the recombinant herpes simplex virus genome further contains inactivating mutations in the ICP0 (one or both copies) and / or UL41 gene.

[0088] In some embodiments, the recombinant herpes simplex virus genome contains an inactivating mutation in the ICP0 (one or both copies) gene. In some embodiments, the recombinant herpes simplex virus genome contains inactivating mutations in the ICP0 (one or both copies) and ICP4 (one or both copies) genes. In some embodiments, the recombinant herpes simplex virus genome contains inactivating mutations in the ICP0 (one or both copies), ICP4 (one or both copies), and ICP22 genes. In some embodiments, the recombinant herpes simplex virus genome contains inactivating mutations in the ICP0 (one or both copies), ICP4 (one or both copies), ICP22, and ICP27 genes. In some embodiments, the recombinant herpes simplex virus genome contains inactivating mutations in the ICP0 (one or both copies), ICP4 (one or both copies), ICP22, ICP27, and UL55 genes. In some embodiments, inactivating mutations in the ICP0 (one or both copies), ICP4 (one or both copies), ICP22, ICP27, and / or UL55 genes include deletions of the coding sequences in the ICP0 (one or both copies), ICP4 (one or both copies), ICP22, ICP27, and / or UL55 genes. In some embodiments, the recombinant herpes simplex virus genome further includes inactivating mutations in the ICP47 and / or UL41 genes.

[0089] In some embodiments, a recombinant herpes simplex virus genome contains one or more polynucleotides of the Disclosure within one, two, three, four, five, six, seven or more viral loci. Examples of preferred viral loci include, but are not limited to, the ICP0 (one or both copies), ICP4 (one or both copies), ICP22, ICP27, ICP47, tk, UL41, and UL55 herpes simplex virus loci. In some embodiments, a recombinant herpes simplex virus genome contains one or more polynucleotides of the Disclosure within one or both loci of the viral ICP4 locus (e.g., a recombinant virus containing a polypeptide-encoding polynucleotide in one or both ICP4 loci). In some embodiments, a recombinant herpes simplex virus genome contains one or more polynucleotides of the Disclosure within the viral ICP22 locus (e.g., a recombinant virus containing a polypeptide-encoding polynucleotide in the ICP22 locus). In some embodiments, the recombinant herpes simplex virus genome contains one or more polynucleotides of the Disclosure within the viral UL41 locus (e.g., a recombinant virus containing a polypeptide-encoding polynucleotide at the UL41 locus). In some embodiments, the recombinant herpes simplex virus genome contains one or more polynucleotides of the Disclosure within the viral ICP27 locus (e.g., a recombinant virus containing a polypeptide-encoding polynucleotide at the ICP27 locus). In some embodiments, the recombinant herpes simplex virus genome contains one or more polynucleotides of the Disclosure within the viral ICP47 locus (e.g., a recombinant virus containing a polypeptide-encoding polynucleotide at the ICP47 locus). In some embodiments, the recombinant herpes simplex virus genome contains one or more polynucleotides of the Disclosure within the viral UL55 locus (e.g., a recombinant virus containing a polypeptide-encoding polynucleotide at the UL55 locus). In some embodiments, the recombinant herpes simplex virus genome contains one or more polynucleotides of the Disclosure within the viral tk locus (e.g., a recombinant virus containing a polypeptide-encoding polynucleotide at the tk locus).

[0090] In some embodiments, the recombinant herpes simplex virus genome contains one or more polynucleotides of the Disclosure in one or both of the viral ICP4 loci and one or more polynucleotides of the Disclosure in the viral ICP22 loci (e.g., a recombinant virus containing a polypeptide-coding polynucleotide in one or both of the ICP4 loci and a polypeptide-coding polynucleotide in the ICP22 loci). In some embodiments, the recombinant herpes simplex virus genome contains one or more polynucleotides of the Disclosure in one or both of the viral ICP4 loci and one or more polynucleotides of the Disclosure in the viral UL41 loci (e.g., a recombinant virus containing a polypeptide-coding polynucleotide in one or both of the ICP4 loci and a polypeptide-coding polynucleotide in the UL41 loci). In some embodiments, the recombinant herpes simplex virus genome contains one or more polynucleotides of the Disclosure in the viral ICP22 loci and one or more polynucleotides of the Disclosure in the viral UL41 loci (e.g., a recombinant virus containing a polypeptide-coding polynucleotide in the ICP22 loci and a polypeptide-coding polynucleotide in the UL41 loci). In some embodiments, the recombinant herpes simplex virus genome comprises one or more polynucleotides of the Disclosure in one or both of the viral ICP4 loci, one or more polynucleotides of the Disclosure in the viral ICP22 loci, and one or more polynucleotides of the Disclosure in the viral UL41 loci (for example, a recombinant virus comprising a polypeptide-encoding polynucleotide in one or both of the ICP4 loci, a polypeptide-encoding polynucleotide in the ICP22 loci, and a polypeptide-encoding polynucleotide in the UL41 loci).In some embodiments, the recombinant herpes simplex virus genome includes one or more polynucleotides of the Disclosure in one or both loci of the viral ICP4 locus, one or more polynucleotides of the Disclosure in the viral ICP22 locus, one or more polynucleotides of the Disclosure in the viral UL41 locus, one or more polynucleotides of the Disclosure in the viral ICP27 locus, one or more polynucleotides of the Disclosure in the viral ICP47 locus, one or more polynucleotides of the Disclosure in the viral tk locus, and / or one or more polynucleotides of the Disclosure in the viral UL55 locus.

[0091] In some embodiments, a recombinant herpesvirus genome (e.g., recombinant herpes simplex virus genome) is engineered to reduce or eliminate the expression of one or more herpesvirus genes (e.g., one or more virulent herpesvirus genes), such as one or both copies of the HSV ICP0 gene, one or both copies of the HSV ICP4 gene, the HSV ICP22 gene, the HSV UL41 gene, the HSV ICP27 gene, the HSV ICP47 gene, the HSV tk gene, the HSV UL55 gene, etc. In some embodiments, a recombinant herpesvirus genome (e.g., recombinant herpes simplex virus genome) is engineered to reduce the cytotoxicity of the recombinant genome (e.g., when introduced into target cells) compared to the corresponding wild-type herpesvirus genome (e.g., wild-type herpes simplex virus genome). In some embodiments, the target cells are human cells (primary cells or cell lines derived therefrom). In some embodiments, the target cells are eye cells (primary cells or cell lines derived therefrom). In some embodiments, the cytotoxicity (e.g., in target cells) of a recombinant genome (e.g., recombinant herpes simplex virus genome) is reduced by at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 99% compared to the corresponding wild-type herpes simplex virus genome (e.g., measuring the relative cytotoxicity of a recombinant ΔICP4 (one or both copies) herpes simplex virus genome to a wild-type herpes simplex virus genome in target cells; measuring the relative cytotoxicity of a recombinant ΔICP4 (one or both copies) / ΔICP22 herpes simplex virus genome to a wild-type herpes simplex virus genome in target cells, etc.).In some embodiments, the cytotoxicity (e.g., in target cells) of recombinant herpes genomes (e.g., recombinant herpes simplex virus genomes) is at least about 1.5 times, at least about 2 times, at least about 3 times, at least about 4 times, at least about 5 times, at least about 6 times, at least about 7 times, at least about 8 times, at least about 9 times, at least about 10 times, at least about 15 times, at least about 20 times, at least about 25 times, at least about 50 times, at least about 75 times, and less than that of the corresponding wild-type herpesvirus genome. The reduction is at least 100 times, at least 250 times, at least 500 times, at least 750 times, at least 1000 times, or more (e.g., measuring the relative cytotoxicity of recombinant ΔICP4 (one or both copies) herpes simplex virus genome to wild-type herpes simplex virus genome in target cells; measuring the relative cytotoxicity of recombinant ΔICP4 (one or both copies) / ΔICP22 herpes simplex virus genome to wild-type herpes simplex virus genome in target cells, etc.). Methods for measuring cytotoxicity are known to those skilled in the art, including, for example, those using biological dyes (formazan dyes), protease biomarkers, MTT assays (or assays using related tetrazolium salts such as XTT, MTS, water-soluble tetrazolium salts, etc.), and those measuring ATP content.

[0092] In some embodiments, recombinant genomes (e.g., recombinant herpes simplex virus genomes) are engineered to reduce the effect on target cell proliferation after exposure to the recombinant genome compared to the corresponding wild-type genome (e.g., wild-type herpes simplex virus genome). In some embodiments, the target cells are human cells (primary cells or cell lines derived therefrom). In some embodiments, the target cells are eye cells (primary cells or cell lines derived therefrom). In some embodiments, target cell proliferation after exposure to a recombinant genome is at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 99% faster than target cell proliferation after exposure to a corresponding wild-type genome (e.g., measuring relative cell proliferation after exposure to a recombinant ΔICP4 (one or both copies) herpes simplex virus genome compared to cell proliferation after exposure to a wild-type herpes simplex virus genome in target cells; measuring relative cell proliferation after exposure to a recombinant ΔICP4 (one or both copies) / ΔICP22 herpes simplex virus genome compared to cell proliferation after exposure to a wild-type herpes simplex virus genome in target cells, etc.).In some embodiments, target cell proliferation after exposure to a recombinant genome is at least about 1.5 times, at least about 2 times, at least about 3 times, at least about 4 times, at least about 5 times, at least about 6 times, at least about 7 times, at least about 8 times, at least about 9 times, at least about 10 times, at least about 15 times, at least about 20 times, at least about 25 times, at least about 50 times, at least about 75 times, at least about 100 times, at least about 250 times, at least about 500 times, at least about 750 times, or at least about 1000 times faster (e.g., measuring relative cell proliferation after exposure to a recombinant ΔICP4 (one or both copies) herpes simplex virus genome compared to cell proliferation after exposure to a wild-type herpes simplex virus genome in target cells; measuring relative cell proliferation after exposure to a recombinant ΔICP4 (one or both copies) / ΔICP22 herpes simplex virus genome compared to cell proliferation after exposure to a wild-type herpes simplex virus genome in target cells, etc.). Methods for measuring cell proliferation are known to those skilled in the art, including, for example, those using the Ki67 cell proliferation assay and the BrdU cell proliferation assay.

[0093] A vector (e.g., a herpesvirus vector) may contain one or more polynucleotides of the present disclosure in a form suitable for polynucleotide expression in a host cell. The vector may also contain one or more regulatory sequences functionally linked to the polynucleotide to be expressed (e.g., as described above).

[0094] In some aspects, this disclosure relates to one or more heterologous polynucleotides (e.g., bacterial artificial chromosomes (BACs)) comprising any of the recombinant nucleic acids described herein.

[0095] In some embodiments, the recombinant nucleic acids of this disclosure (e.g., recombinant herpes simplex virus genome) include one or more of the polynucleotides described herein inserted into the recombinant nucleic acid in any orientation. If the recombinant nucleic acid includes two or more polynucleotides described herein (e.g., two or more, three or more, etc.), the polynucleotides may be inserted in the same orientation or in opposite orientations to each other. While we do not wish to be bound by theory, incorporating two polynucleotides (e.g., two transgenes) into a recombinant nucleic acid (e.g., a vector) in antisense orientation may help avoid read-through and ensure proper expression of each polynucleotide.

[0096] In some embodiments, the recombinant nucleic acids of the Disclosure do not contain polynucleotides encoding collagen α-1(VII) chain polypeptide (COL7). In some embodiments, the recombinant nucleic acids of the Disclosure do not contain polynucleotides encoding lysyl hydroxylase 3 polypeptide (LH3). In some embodiments, the recombinant nucleic acids of the Disclosure do not contain polynucleotides encoding keratin type I cytoskeleton 17 polypeptide (KRT17). In some embodiments, the recombinant nucleic acids of the Disclosure do not contain polynucleotides encoding transglutaminase (TGM) polypeptides (e.g., human transglutaminase polypeptides, e.g., human TGM1 polypeptide and / or human TGM5 polypeptide). In some embodiments, the recombinant nucleic acids of the Disclosure do not contain polynucleotides encoding cosmetic proteins (e.g., collagen protein, fibronectin, elastin, lumican, vitronectin / vitronectin receptor, laminin, neuromodulators, fibrillin, further skin extracellular matrix proteins, etc.). In some embodiments, the recombinant nucleic acids of the Disclosure do not contain polynucleotides encoding antibodies (e.g., full-length antibodies, antibody fragments, etc.). In some embodiments, the recombinant nucleic acids of the Disclosure do not contain polynucleotides encoding serine protease inhibitor Kazal-type (SPINK) polypeptides (e.g., human SPINK polypeptides such as SPINK5 polypeptide). In some embodiments, the recombinant nucleic acids of the Disclosure do not contain polynucleotides encoding filaggrin or filaggrin 2 polypeptides (e.g., human filaggrin or filaggrin 2 polypeptide). In some embodiments, the recombinant nucleic acids of the Disclosure do not contain polynucleotides encoding cystic fibrosis membrane conductance regulator (CFTR) polypeptides (e.g., human CFTR polypeptide). In some embodiments, the recombinant nucleic acids of the Disclosure do not contain polynucleotides encoding ichthyosis-related polypeptides (e.g., ATP-binding cassette subfamily A member 12 polypeptide, 1-acylglycerol-3-phosphate O-acyltransferase ABHD5 polypeptide, aldehyde dehydrogenase family 3 member A2 polypeptide, arachidonic acid 12-lipoxygenase 12R-type polypeptide,Hydroperoxide isomerase ALOXE3 polypeptide, AP-1 complex subunit σ-1A polypeptide, arylsulfatase E polypeptide, caspase-14 polypeptide, cornodesmosine polypeptide, ceramide synthase 3 polypeptide, carbohydrate sulfotransferase 8 polypeptide, claudin-1 polypeptide, cystatin-A polypeptide, cytochrome P450 4F22 polypeptide, 3-β-hydroxysteroid-δ(8),δ(7)-isomerase polypeptide, extra-long chain fatty acid elongation protein 4 polypeptide, filaggrin polypeptide, filaggrin 2 polypeptide, Gap-linked β-2 polypeptide, Gap-linked β-3 polypeptide, Gap-linked β-4 polypeptide, Gap-linked β-6 polypeptide, 3-ketodihydrosphingosine reductase polypeptide, keratin type II cytoskeleton 1 polypeptide, keratin type II cytoskeleton 2 epithelial polypeptide, keratin type I cytoskeleton 9 polypeptide, keratin type I cytoskeleton 10 polypeptide, lipase member N polypeptide, loricrin polypeptide, membrane-bound transcription factor site-2 protease polypeptide, magnesium transporter NIPA4 polypeptide, sterol-4-α-carboxylic acid The recombinant nucleic acids of this disclosure do not contain polynucleotides encoding 3-dehydrogenase, decarboxylation polypeptide, peroxisome targeting signal 2 receptor polypeptide, D-3-phosphoglycerate dehydrogenase polypeptide, phytanoyl-CoA dioxygenase, peroxisome polypeptide, patatin-like phospholipase domain-containing protein 1 polypeptide, proteasome maturation protein polypeptide, phosphoserine aminotransferase polypeptide, short-chain dehydrogenase / reductase family 9C member 7 polypeptide, serpine B 8 polypeptide, long-chain fatty acid transport protein 4 polypeptide, synaptosome-related protein 29 polypeptide, tumorigenicity suppressor 14 protein polypeptide, steryl sulfatase polypeptide, vacuolar protein sorting-related protein 33B polypeptide, and CAAX prenylprotease 1 homolog polypeptide. In some embodiments, the recombinant nucleic acids of this disclosure include collagen α-1(VII) chain polypeptide, lysyl hydroxylase 3 polypeptide,The recombinant nucleic acids of this disclosure do not contain polynucleotides encoding 17 keratin type I cytoskeleton polypeptides and / or any chimeric polypeptides thereof. In some embodiments, the recombinant nucleic acids of this disclosure include collagen α-1(VII) chain polypeptide, lysyl hydroxylase 3 polypeptide, keratin type I cytoskeleton 17 polypeptide, transglutaminase (TGM) polypeptide, filaggrin polypeptide, beauty protein, antibody, SPINK polypeptide, CFTR polypeptide, ichthyosis-related polypeptide, α-1-antitrypsin polypeptide, sodium-dependent phosphate transport protein 2B polypeptide, dynein heavy chain 5-axial polypeptide, dynein heavy chain 11-axial polypeptide, coiled-coil domain-containing protein 39 polypeptide, dynein intermediate chain 1-axial polypeptide, coiled-coil domain-containing protein 40 polypeptide, coiled-coil domain-containing protein 103 polypeptide, sperm-related antigen 1 polypeptide, zinc finger MYND domain-containing protein 10 polypeptide, armadillo repeat-containing protein 4 polypeptide, coiled-coil domain-containing protein 151 polypeptide, dynein intermediate chain 2-axial polypeptide, radial sponge Spokehead 1 homolog polypeptide, Coiled Coil Domain-containing Protein 114 polypeptide, Radial Spokehead Protein 4 homolog A polypeptide, Dynein Assembly Factor 1 Axoneme polypeptide, Dynein Assembly Factor 2 Axoneme polypeptide, Leucine-Rich Repeat-containing Protein 6 polypeptide, Lung Surfactant-Associated Protein B polypeptide, Lung Surfactant-Associated Protein C polypeptide, Homeobox Protein Nkx-2.1 polypeptide, ATP-binding Cassette Subfamily A Member 3 polypeptide, Cytokine Receptor Common Subunit β polypeptide, Granulocyte-Macrophage Colony-Stimulating Factor Receptor Subunit α polypeptide, Osteogenesis Imperative Receptor Type 2 polypeptide, Sarplasmosis / Endoplasmic Reticulum Calcium ATPase 2 polypeptide, Serine / Threonine-Protein Kinase Receptor R3 polypeptide, Endoglin polypeptide, Decapentaplesic Maternal Homolog 9 polypeptide, Caveolin-1 polypeptide, Potassium Channel Subfamily K Member 3 polypeptide,It does not contain polynucleotides encoding eIF-2-α kinase GCN2 polypeptide, lung surfactant-associated protein A2 polypeptide, telomerase reverse transcriptase polypeptide, diskelin polypeptide, telomere elongation helicase 1 regulator polypeptide, poly(A)-specific ribonuclease PARN polypeptide, TERF1 interacting nuclear factor 2 polypeptide, H / ACA ribonucleoprotein complex noncore subunit NAF1 polypeptide, mucin-5B polypeptide, desmoplakin polypeptide, CST complex subunit STN1 polypeptide, dipeptidyl peptidase 9 polypeptide, and / or any chimeric polypeptides thereof.

[0097] In some embodiments, the recombinant nucleic acids of the Disclosure do not contain polynucleotides encoding immunomodulatory polypeptides. In some embodiments, the recombinant nucleic acids of the Disclosure do not contain polynucleotides encoding cytokine polypeptides and / or chemokine polypeptides. In some embodiments, the recombinant nucleic acids of the Disclosure do not contain polynucleotides encoding cytokine polypeptides. In some embodiments, the recombinant nucleic acids of the Disclosure do not contain polynucleotides encoding IL-1 polypeptide, IL-2 polypeptide, IL-7 polypeptide, IL-12 polypeptide, IL-13 polypeptide, IL-15 polypeptide, IL-17 polypeptide, IL-18 polypeptide, IL-28 polypeptide, IL-32 polypeptide, IL-33 polypeptide, IL-34 polypeptide, TNFα polypeptide, IFNγ polypeptide, G-CSF polypeptide, GM-CSF polypeptide, and / or any chimeric polypeptide thereof.

[0098] In some embodiments, the recombinant nucleic acids of the Disclosure do not contain polynucleotides encoding chemokine polypeptides. In some embodiments, the recombinant nucleic acids of the Disclosure do not contain polynucleotides encoding CXCL1 polypeptide, CXCL2 polypeptide, CXCL8 polypeptide, CXCL9 polypeptide, CXCL11 polypeptide, CXCL16 polypeptide, CCL2 polypeptide, CCL3 polypeptide, CCL4 polypeptide, CCL5 polypeptide, CCL11 polypeptide, and / or any chimeric polypeptide thereof.

[0099] IV. Viruses Certain aspects of this disclosure relate to viruses comprising any of the polynucleotides and / or recombinant nucleic acids described herein. In some embodiments, the virus is capable of infecting one or more target cells of a subject (e.g., human). In some embodiments, the virus is suitable for delivering polynucleotides and / or recombinant nucleic acids to one or more target cells of a subject (e.g., human). In some embodiments, the one or more target cells are human cells. In some embodiments, the one or more target cells are one or more cells of the eye (e.g., anterior chamber; posterior chamber; ciliary body; corneal epithelial cells; rod cells; cone cells; photoreceptors; retinal pigment epithelial cells; retinal ganglion cells; bipolar cells; horizontal cells; Müller cells; axonless cells; etc.).

[0100] Any suitable virus known in the art may be used, for example, including adenoviruses, adeno-associated viruses, retroviruses, lentiviruses, Sendai viruses, papillomaviruses, herpesviruses (e.g., herpes simplex virus), vaccinia viruses, and / or any hybrid or derivative viruses thereof. In some embodiments, the virus is attenuated. In some embodiments, the virus is reproducible. In some embodiments, the virus is replication-deficient. In some embodiments, the virus is not oncolytic. In some embodiments, the virus is modified to alter its tissue affinity compared to the corresponding unmodified wild-type virus. In some embodiments, the virus has reduced cytotoxicity (e.g., in target cells) compared to the corresponding wild-type virus. Methods for producing viruses containing recombinant nucleic acids are well known to those skilled in the art.

[0101] In some embodiments, the virus is a member of the Herpesviridae family of DNA viruses, including, for example, herpes simplex virus, varicella-zoster virus, human cytomegalovirus, herpesvirus 6A, herpesvirus 6B, herpesvirus 7, Epstein-Barr virus, and Kaposi's sarcoma-associated herpesvirus. In some embodiments, the herpesvirus is attenuated. In some embodiments, the herpesvirus is replication-deficient. In some embodiments, the herpesvirus is replication-capable. In some embodiments, the herpesvirus is replication-capable. In some embodiments, the herpesvirus is engineered to reduce or eliminate the expression of one or more herpesvirus genes (e.g., one or more virulent herpesvirus genes). In some embodiments, the herpesvirus has reduced cytotoxicity compared to the corresponding wild-type herpesvirus. In some embodiments, the herpesvirus is not oncolytic.

[0102] In some embodiments, the virus is herpes simplex virus. Herpes simplex virus containing recombinant nucleic acid may be produced by processes disclosed, for example, in WO2015 / 009952, WO2017 / 176336, WO2019 / 200163, and / or WO2019 / 210219. In some embodiments, the herpes simplex virus is attenuated. In some embodiments, the herpes simplex virus is replication-deficient. In some embodiments, the herpes simplex virus is replication-capable. In some embodiments, the herpes simplex virus is replication-capable. In some embodiments, the herpes simplex virus is engineered to reduce or eliminate the expression of one or more herpes simplex virus genes (e.g., one or more virulent herpes simplex virus genes). In some embodiments, the herpes simplex virus has reduced cytotoxicity compared to the corresponding wild-type herpes simplex virus. In some embodiments, the herpes simplex virus is not oncolytic. In some embodiments, the herpes simplex virus is HSV-1, HSV-2, or any derivative thereof. In some embodiments, the herpes simplex virus is the HSV-1 virus. In some embodiments, HSV-1 is attenuated. In some embodiments, HSV-1 is replication-deficient. In some embodiments, HSV-1 is replication-capable. In some embodiments, HSV-1 is engineered to reduce or eliminate the expression of one or more HSV-1 genes (e.g., one or more toxic HSV-1 genes). In some embodiments, HSV-1 has reduced cytotoxicity compared to the corresponding wild-type HSV-1. In some embodiments, HSV-1 is not oncolytic.

[0103] In some embodiments, the herpes simplex virus is modified to alter its tissue affinity relative to that of unmodified wild-type herpes simplex virus. In some embodiments, the herpes simplex virus includes a modified envelope. In some embodiments, the modified envelope includes one or more (e.g., one or more, two or more, three or more, four or more, etc.) variant herpes simplex virus glycoproteins. Examples of herpes simplex virus glycoproteins may include, but are not limited to, glycoproteins gB, gC, gD, gH, and gL. In some embodiments, the modified envelope alters the herpes simplex virus tissue affinity relative to that of wild-type herpes simplex virus.

[0104] In some embodiments, the transduction efficiency (in vitro and / or in vivo) of the virus of the Disclosure (e.g., a herpesvirus such as herpes simplex virus) to one or more target cells (e.g., one or more cells of the eye) is at least about 25%. For example, the transduction efficiency of the virus to one or more target cells may be at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 99%, at least about 99.5%, or higher. In some embodiments, the virus is a herpes simplex virus, and the transduction efficiency of the virus to one or more target cells (e.g., one or more cells of the eye) is about 85% to about 100%. In some embodiments, the virus is a herpes simplex virus, and the transduction efficiency of the virus to one or more target cells (e.g., one or more cells of the eye) is at least about 85%, at least about 86%, at least about 87%, at least about 88%, at least about 89%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or 100%. Methods for measuring the transduction efficiency of the virus in vitro or in vivo are well known to those skilled in the art, including, for example, qPCR analysis, deep sequencing, Western blotting, and fluorescence quantitative analysis (e.g., fluorescence in situ hybridization (FISH), fluorescence reporter gene expression, immunofluorescence, FACS).

[0105] In some embodiments, recombinant viruses, which may or may not be pseudotyped, that produce one or more therapeutic polypeptides for the treatment of eye conditions or diseases are provided herein. In some embodiments, one or more therapeutic polypeptides produced by the recombinant viruses described herein mediate or enhance the treatment of eye conditions or diseases. The disclosure further provides therapeutic compositions comprising the recombinant viruses and methods of use in the treatment of eye conditions or diseases.

[0106] V. Pharmaceutical Compositions and Formulations Certain aspects of the disclosure relate to pharmaceutical compositions or formulations comprising any of the recombinant nucleic acids (e.g., recombinant herpesvirus genomes) and / or viruses (e.g., herpesviruses comprising recombinant genomes) described herein (such as herpes simplex virus comprising a recombinant herpes simplex virus genome) and a pharmaceutically acceptable excipient or carrier.

[0107] In some embodiments, the pharmaceutical composition or formulation comprises any one or more of the viruses (e.g., herpesviruses) described herein. In some embodiments, the pharmaceutical composition or formulation comprises from about 10 4 to about 10 12 plaque forming units (PFU) / mL of virus. For example, the pharmaceutical composition or formulation comprises from about 10 4 to about 10 12 , from about 10 5 to about 10 12 , from about 10 6 to about 10 12 , from about 10 7 to about 10 12 , from about 10 8 to about 10 12 , from about 10 9 to about 10 12 , from about 10 10 to about 10 12 , from about 10 11 to about 10 12 , from about 10 4 to about 10 11 , from about 10 5 to about 10 11 , from about 106 ~about 10 11 , about 10 7 ~about 10 11 , about 10 8 ~about 10 11 , about 10 9 ~about 10 11 , about 10 10 ~about 10 11 , about 10 4 ~about 10 10 , about 10 5 ~about 10 10 , about 10 6 ~about 10 10 , about 10 7 ~about 10 10 , about 10 8 ~about 10 10 , about 10 9 ~about 10 10 , about 10 4 ~about 10 9 , about 10 5 ~about 10 9 , about 10 6 ~about 10 9 , about 10 7 ~about 10 9 , about 10 8 ~about 10 9 , about 10 4 ~about 10 8 , about 10 5 ~about 10 8 , about 10 6 ~approximately 108, approximately 10 7 ~about 10 8 , about 10 4 ~about 10 7 , about 10 5 ~about 10 7 , about 10 6 ~about 10 7 , about 10 4 ~about 10 6 , about 10 5 ~about 10 6 , or about 10 4 ~about 10 5 It may contain PFU / mL of virus. In some embodiments, the pharmaceutical composition or formulation may contain about 10 4 , about 10 5 , about 10 6 , about 10 7 , about 10 8 , about 109 , about 10 10 , about 10 11 , or about 10 12 Contains PFU / mL of virus.

[0108] Pharmaceutical compositions and formulations can be prepared by mixing an active ingredient (such as recombinant nucleic acids and / or viruses) of desired purity with one or more pharmaceutically acceptable carriers or excipients. Pharmaceutically acceptable carriers or excipients are generally non-toxic to the recipient at the dosage and concentration used and include: buffers (such as phosphoric acid, citrate, acetic acid, and other organic acids); antioxidants (such as ascorbic acid and methionine); preservatives (such as octadecyldimethylbenzylammonium chloride, benzalkonium chloride, benzethonium chloride, phenol, butyl or benzyl alcohol, alkylparabens, catechol, resorcinol, cyclohexanol, 3-pentanol, and m-cresol); amino acids (such as glycine, glutamine, asparagine, histidine, arginine, or lysine); low molecular weight (less than about 10 residues) polypeptides; and proteins (serum albumin). This may include, but is not limited to, pharmaceutically acceptable carriers such as: gelatin, immunoglobulins, etc.; polyols (such as glycerol, e.g., formulations containing glycerol in concentrations of 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%); hydrophilic polymers (such as polyvinylpyrrolidone); monosaccharides, disaccharides, and other hydrocarbons (including glucose, mannose, or dextrin); chelating agents (such as EDTA); sugars (such as sucrose, mannitol, trehalose, or sorbitol); salt-forming counterions (such as sodium); metal complexes (such as Zn-protein complexes); and / or nonionic surfactants (such as polyethylene glycol (PEG)). A detailed discussion of pharmaceutically acceptable carriers is available in REMINGTON'S PHARMACEUTICAL SCIENCES (Mack Pub. Co., NJ 1991).

[0109] In some embodiments, the pharmaceutical composition or formulation is suitable for use as eye drops, ointments, pastes, creams, suspensions, emulsions, fatty ointments, gels, bioadhesive gels, powders, lotions, solutions, and / or sprays.

[0110] In some embodiments, the pharmaceutical composition or formulation comprises one or more lipid (e.g., cationic lipid) carriers. In some embodiments, the pharmaceutical composition or formulation comprises one or more nanoparticle carriers. Nanoparticles are submicron (less than about 1000 nm) sized drug delivery vehicles capable of carrying encapsulated drugs (such as synthetic small molecules, proteins, peptides, cells, viruses, and nucleic acid-based biotherapeutic agents) for rapid or controlled release. A variety of molecules (e.g., proteins, peptides, recombinant nucleic acids, etc.) can be efficiently encapsulated in nanoparticles using processes well known in the art. In some embodiments, a molecule "encapsulated" in a nanoparticle may mean a molecule (such as a virus) that is contained within the nanoparticle, or attached to and / or associated with the surface of the nanoparticle, or any combination thereof. Nanoparticles for use in the compositions or formulations described herein may be any type of biocompatible nanoparticle known in the art, including, for example, nanoparticles containing poly(lactic acid), poly(glycolic acid), PLGA, PLA, PGA, and any combination thereof (see, for example, Vauthier et al. Adv Drug Del Rev. (2003) 55: 519-48; US2007 / 0148074; US2007 / 0092575; US2006 / 0246139; US5753234; US7081483; and WO2006 / 052285).

[0111] In some embodiments, pharmaceutically acceptable carriers or excipients may be adapted to or suitable for any route of administration known in the art, including, for example, ocular, subretinal, intraocular, intravitreous, topical, subcutaneous, subconjunctival, sub-Tenon's capsule, sub-Tenon's capsule, intrachorporeal, retrobulbar, systemic, parenteral, periocular, periscleral, anterior scleral, posterior scleral, oral, peribulbar, or choroidal administration.

[0112] In some embodiments, pharmaceutically acceptable carriers or excipients may be adapted to or suitable for any route of administration known in the art, including, for example, intravenous, intramuscular, subcutaneous, cutaneous, oral, intranasal, intratracheal, sublingual, buccal, topical, transdermal, intradermal, intraperitoneal, intraorbital, intravitreous, subretinal, suprachoroidal, transmucosal, intra-articular, implantable, inhaled, intrathecal, intraventricular, and / or intranasal administration.

[0113] In some embodiments, the pharmaceutical composition or formulation may be adapted to or suitable for any route of administration known in the art, including, for example, intravenous, intramuscular, subcutaneous, cutaneous, oral, intranasal, intratracheal, sublingual, buccal, topical, transdermal, intradermal, intraperitoneal, intraorbital, intravitreous, subretinal, suprachoroidal, transmucosal, intra-articular, implantable, inhaled, intrathecal, intraventricular, or intranasal administration.

[0114] In some embodiments, the pharmaceutical composition or formulation further comprises one or more additional components. Examples of additional ingredients may include, but are not limited to, binders (e.g., pregelatinized corn starch, polyvinylpyrrolidone, or hydroxypropyl methylcellulose); fillers (e.g., lactose and other sugars, microcrystalline cellulose, pectin, gelatin, calcium sulfate, ethylcellulose, polyacrylate, or calcium hydrogen phosphate); lubricants (e.g., magnesium stearate, talc, silica, colloidal silicon dioxide, stearic acid, metal stearate, hydrogenated vegetable oil, corn starch, polyethylene glycol, sodium benzoate, sodium acetate, etc.); disintegrants (e.g., starch, sodium starch glycolate, etc.); humectants (e.g., sodium lauryl sulfate, etc.); salt solutions; alcohols; polyethylene glycol; gelatin; lactose; amylase; magnesium stearate; talc; silicic acid; viscous paraffin; hydroxymethylcellulose; polyvinylpyrrolidone; sweeteners; flavorings; fragrances; colorants; humectants; sunscreens; antibacterial agents; and active ingredients that can stabilize polynucleotides or prevent their degradation. In some embodiments, the pharmaceutical composition or formulation comprises a methylcellulose gel (e.g., hydroxypropylmethylcellulose, carboxymethylcellulose, etc.). In some embodiments, the pharmaceutical composition or formulation comprises a phosphate buffer. In some embodiments, the pharmaceutical composition or formulation comprises glycerol (e.g., about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 12%, about 13%, about 14%, about 15%, etc.). In some embodiments, the pharmaceutical composition or formulation comprises a phosphate buffer and glycerol.

[0115] Pharmaceutical compositions and formulations intended for in vivo administration are generally sterile. Sterility can be easily achieved, for example, by filtration through a sterile filtration membrane.

[0116] In some embodiments, one or more polynucleotides encoding a polypeptide can be delivered to one or more cells of a subject (e.g., one or more cells of the eye of a subject) using any of the recombinant nucleic acids, viruses and / or pharmaceutical compositions or formulations described herein. In some embodiments, the subject suffers from an eye condition or disease. In some embodiments, any of the recombinant nucleic acids, viruses and / or pharmaceutical compositions or formulations described herein can be delivered to retinitis pigmentosa, recessive retinitis pigmentosa, severe recessive retinitis pigmentosa, dominant retinitis pigmentosa, dominant retinitis pigmentosa with choroidal lesions, recessive retinitis pigmentosa with paraarteriolar preservation of RPE (PPRPE), recessive retinitis pigmentosa with posterior column ataxia (PCARP), recessive retinitis pigmentosa with microcytosis, symptomatic recessive retinitis pigmentosa, and recessive retinitis pigmentosa. Symptomatic disease, non-symptomatic recessive retinitis pigmentosa, non-symptomatic dominant retinitis pigmentosa, symptomatic dominant retinitis pigmentosa, juvenile recessive retinitis pigmentosa, recessive retinitis pigmentosa and intellectual disability, recessive retinitis pigmentosa with macular degeneration, severe early-onset recessive retinitis pigmentosa, recessive retinitis pigmentosa and bone malformations, recessive retinitis pigmentosa and skeletal abnormalities, dominant retinitis pigmentosa with sensorineural hearing loss, recessive retinitis pigmentosa with hearing loss, recessive retinitis pigmentosa with hearing loss and additional disability, recessive retinitis pigmentosa with vitreous degeneration , early-onset recessive retinitis pigmentosa with macular defect, X-linked retinitis pigmentosa, recessive X-linked retinitis pigmentosa, dominant X-linked retinitis pigmentosa, severe X-linked retinitis pigmentosa, X-linked retinitis pigmentosa with intellectual disability, X-linked retinitis pigmentosa with myopathy, Valday-Beedl-like retinitis pigmentosa, Valday-Beedl-like recessive retinitis pigmentosa, bigenic retinitis pigmentosa, bigenic retinitis pigmentosa with retinal outer segment membrane protein 1, bigenic retinitis pigmentosa with PRPH2, recessive retinitis pigmentosa with early macular lesions, recessive hearing loss without retinitis pigmentosa, recessive congenital hearing loss without retinitis pigmentosa, recessive retinitis pigmentosa and recessive ataxia, recessive retinitis pigmentosa and dominant ataxia, mitochondrial retinitis pigmentosa, mitochondrial retinitis pigmentosa with developmental and neurological abnormalities, mitochondrial retinitis pigmentosa with progressive sensorineural hearing loss, mitochondrial retinitis pigmentosa with hearing loss and neurological abnormalities, autosomal dominant retinitis pigmentosa, non-symptomatic autosomal dominant retinitis pigmentosa,Autosomal recessive retinitis pigmentosa, non-syndromic autosomal recessive retinitis pigmentosa, retinal pigment epithelium (RPE), recessive RPE, dominant RPE, recessive RPE degeneration, dominant RPE degeneration, ataxia, recessive ataxia, dominant ataxia, Senior-Loken syndrome, recessive Senior-Loken syndrome, dominant Senior-Loken syndrome, nephronoplasia, recessive nephronoplasia, dominant nephronoplasia, adolescent recessive nephronoplasia, ciliopathy-associated recessive nephronoplasia, juvenile nephronoplasia, juvenile recessive nephronoplasia, juvenile dominant nephronoplasia, Usher syndrome, Usher syndrome type I, Usher syndrome type II, Usher syndrome Group III, recessive Usher syndrome, atypical recessive Usher syndrome, dominant Usher syndrome, type 2 recessive Usher syndrome, type 2a recessive Usher syndrome, type 3 recessive Usher syndrome, type 3-like recessive Usher syndrome, atypical recessive Usher syndrome, type 1 recessive Usher syndrome, type 1b recessive Usher syndrome, type 1d recessive Usher syndrome, type 1f recessive Usher syndrome, type 1J recessive Usher syndrome, type 1k recessive Usher syndrome, dizygotic Usher syndrome with CDH23, dizygotic Usher syndrome with PCDH15, acadian recessive Usher syndrome, recessive atypical Usher syndrome (USH3-like), Leber's congenital amaurosis, recessive Leber's congenital amaurosis, dominant Leber's congenital amaurosis, de novo Leber's congenital amaurosis, dominant Leber's congenital amaurosis with pituitary dysfunction, recessive Leber's congenital amaurosis with myopathy, recessive Leber's congenital amaurosis with severe childhood retinal dystrophy, mitochondrial Leber hereditary optic neuropathy, Leber's hereditary optic neuropathy, optic nerve atrophy, recessive optic nerve atrophy, dominant optic nerve atrophy, optic nerve atrophy with ataxia, recessive optic nerve atrophy with ataxia, with ataxia Dominant optic atrophy, recessive optic atrophy with ataxia and 3-methylglutaconic aciduria, dominant optic atrophy with cataracts, ataxia and anreflexia, Kahr-type dominant optic atrophy, dominant optic atrophy with sensorineural hearing loss, recessive cerebellar degeneration with optic atrophy, optic atrophy with anesthesia-dystonia syndrome, X-linked optic atrophy with anesthesia-dystonia syndrome, retinal dystrophy, recessive retinal dystrophy, dominant retinal dystrophy, hereditary retinal dystrophy, early-onset recessive retinal dystrophy, recessive symptomatic retinal dystrophy, recessive non-symptomatic retinal dystrophy,Recessive symptomatic and asymptomatic retinal dystrophy, recessive optic atrophy and retinal dystrophy, recessive retinal dystrophy and obesity, recessive retinal dystrophy and cerebellar dysplasia, symptomatic recessive optic atrophy and retinal dystrophy, dominant retinal dystrophy with iris defects, ciliopathy spectrum including retinal dystrophy, recessive ciliopathy spectrum including retinal dystrophy, dominant ciliopathy spectrum including retinal dystrophy, dominant optic atrophy with neuropathy and myopathy, dominant optic atrophy with intellectual disability and developmental delay, symptomatic optic atrophy , non-symptomatic optic nerve atrophy, recessive non-symptomatic optic nerve atrophy, dominant non-symptomatic optic nerve atrophy, recessive symptomatic optic nerve atrophy, dominant symptomatic optic nerve atrophy, Charcot-Marie-Tooth disease, recessive Charcot-Marie-Tooth disease, dominant Charcot-Marie-Tooth disease, benign spotted retina, recessive benign spotted retina, dominant benign spotted retina, symptomatic retinopathy, recessive symptomatic retinopathy, dominant symptomatic retinopathy, Batten disease, recessive Batten disease, dominant Batten disease, recessive Batten disease (neuroceroid lipofuscinosis type 3), juvenile recessive Batten disease (neuroceroid lipofuscinosis type 3), neuroceroid lipofuscinosis, recessive Ceroid lipofuscinosis of the nervous system, recessive ceroid lipofuscinosis type 1, dominant ceroid lipofuscinosis, Stargart disease, recessive Stargart disease, dominant Stargart disease, juvenile Stargart disease, late-onset Stargart disease, Stargart-like macular dystrophy, recessive Stargart-like macular dystrophy, dominant Stargart-like macular dystrophy, macular dystrophy, recessive macular dystrophy, early-onset macular dystrophy, adult-onset macular dystrophy, early-onset recessive macular dystrophy, adult-onset recessive macular dystrophy, early adult-onset recessive macular dystrophy Sexual macular dystrophy, juvenile recessive macular dystrophy with hypotrichosis, dominant macular dystrophy, late-onset dominant macular dystrophy, dominant macular dystrophy with lens zonules, bullseye dominant macular dystrophy, butterfly-shaped dominant macular dystrophy, age-related dominant macular dystrophy, benign concentric annular dominant macular dystrophy, vitelloid recessive macular dystrophy, vitelloid dominant macular dystrophy, atypical vitelloid dominant macular dystrophy, dominant adult-type vitelloid macular dystrophy, Stargard-type dominant macular dystrophy, Stargard-type dominant macular dystrophy,North Carolina dominant macular dystrophy, North Carolina-like dominant macular dystrophy, North Carolina-like dominant macular dystrophy with progressive sensorineural hearing loss, cystoid dominant macular dystrophy, Best-type dominant macular dystrophy, occult macular dystrophy, recessive occult macular dystrophy, dominant occult macular dystrophy, age-related familial macular dystrophy, X-linked atrophic macular dystrophy, recessive X-linked atrophic macular dystrophy, dominant X-linked atrophic macular dystrophy, mitochondrial macular pattern dystrophy with type II diabetes and hearing loss Rophy, yellow spot fundus, recessive yellow spot fundus, dominant yellow spot fundus, rod dystrophy, recessive rod dystrophy, dominant rod dystrophy, cone dystrophy, recessive cone dystrophy, dominant cone dystrophy, recessive cone dystrophy with supernormal rod electroretinogram, early-onset recessive cone dystrophy, late-onset recessive cone dystrophy, cone dystrophy 1, X-linked cone dystrophy 1, cone dystrophy 2, progressive cone dystrophy 2, X-linked progressive cone dystrophy 2, delayed cone adaptation, recessive delayed cone adaptation, dominant delayed cone adaptation, cone rod Rod-condylophysical dystrophy, recessive rod-condylophysical dystrophy, dominant rod-condylophysical dystrophy, solitary rod-condylophysical dystrophy, progressive rod-condylophysical dystrophy, X-linked rod-condylophysical dystrophy, X-linked progressive rod-condylophysical dystrophy, progressive dominant rod-condylophysical dystrophy, rod-condylophysical dystrophy and enamel hypoplasia syndrome, recessive rod-condylophysical dystrophy and enamel hypoplasia syndrome, dominant rod-condylophysical dystrophy and enamel hypoplasia syndrome, recessive rod-condylophysical dystrophy with internal retinopathy, recessive rod-condylophysical dystrophy with bone disease, congenital disorders Symptomatic non-progressive recessive pyramidal-rodylosis, recessive pyramidal-rodylosis with hearing loss, recessive pyramidal-rodylosis with psychomotor retardation, recessive pyramidal and pyramidal-rodylosis, pyramidal-rodylosis synaptic disease, congenital pyramidal-rodylosis synaptic disease, recessive congenital pyramidal-rodylosis synaptic disease, dominant congenital pyramidal-rodylosis synaptic disease, rod-pyramidal dystrophy, recessive rod-pyramidal dystrophy, dominant rod-pyramidal dystrophy, early-onset recessive rod-pyramidal dystrophy, non-symptomatic recessive rod-pyramidal dystrophy, recessive Newfoundland rod-pyramidal dystrophy, recessive progressive pyramidal dystrophy,Stickler syndrome, dominant Stickler syndrome, recessive Stickler syndrome, dominant Stickler syndrome type I, dominant Stickler syndrome type II, Marshall syndrome, dominant Marshall syndrome, recessive Marshall syndrome, monochromacy, recessive monochromacy, dominant monochromacy, recessive complete monochromacy, recessive incomplete monochromacy, macular degeneration, age-related macular degeneration, complex etiology age-related macular degeneration, isolated age-related macular degeneration, wet age-related macular degeneration, dry age-related macular degeneration, drusen, recessive drusen, dominant drusen, early-onset recessive drusen, early Dominant drusen, macular drusen, dominant radial macular drusen, pigmentary paravenous retinal choroidal atrophy, recessive pigmentary paravenous retinal choroidal atrophy, dominant pigmentary paravenous retinal choroidal atrophy, progressive bifocal retinal choroidal atrophy, Valday-Beedl syndrome, recessive Valday-Beedl syndrome, dominant Valday-Beedl syndrome, recessive Valday-Beedl syndrome with developmental abnormalities, retinal degeneration, recessive retinal degeneration, dominant retinal degeneration, non-symptomatic recessive retinal degeneration, Doynn's honeycomb retinal degeneration, Doynn's recessive honeycomb retinal degeneration, Doynn's dominant honeycomb retinal degeneration (Malattiya) Leventinese), recessive nephronoplasia with retinal degeneration, Alström syndrome, recessive Alström syndrome, dominant Alström syndrome, Joubert syndrome, recessive Joubert syndrome, dominant Joubert syndrome, Joubert syndrome, recessive Joubert syndrome, dominant Joubert syndrome, X-linked Joubert syndrome, vitreoretinal degeneration, recessive vitreoretinal degeneration, dominant vitreoretinal degeneration, snowflake vitreoretinal degeneration, snowflake dominant vitreoretinal degeneration, Oguchi disease, recessive Oguchi disease, dominant Oguchi disease, night blindness, stasis night blindness, congenital night blindness, congenital stasis night blindness, severe congenital stasis night blindness, recessive congenital stasis night blindness, recessive complete type Congenital congenital nyctalopsia, dominant congenital nyctalopsia, Nogarette type dominant congenital nyctalopsia, Oguchi type recessive congenital nyctalopsia, Riggs type recessive congenital nyctalopsia, Schubert-Bornschein type recessive congenital nyctalopsia, white punctate fundus type recessive congenital nyctalopsia, complete recessive congenital nyctalopsia, X-linked congenital nyctalopsia, incomplete X-linked congenital nyctalopsia, retinal vascular disease, cerebral leukodystrophy, retinal vascular disease with cerebral leukodystrophy, recessive retinal vascular disease with cerebral leukodystrophy, dominant retinal vascular disease with cerebral leukodystrophy, Eicardi-Gutierre syndrome, Eicardi-Gutierre syndrome 1,Recessive Eycardi-Gutierre syndrome 1, dominant Eycardi-Gutierre syndrome 1, lupus frostbite, recessive lupus frostbite, dominant lupus frostbite, Martinique retinal dystrophy and retinitis pigmentosa, recessive Martinique retinal dystrophy and retinitis pigmentosa, dominant Martinique retinal dystrophy and retinitis pigmentosa, spinocerebellar ataxia, recessive spinocerebellar ataxia, dominant spinocerebellar ataxia, spinocerebellar ataxia with macular dystrophy, spinocerebellar ataxia with retinal degeneration, macular dystrophy or retinal degeneration, Spinocerebellar ataxia with macular dystrophy or retinal degeneration, recessive spinocerebellar ataxia with macular dystrophy or retinal degeneration, dominant spinocerebellar ataxia with macular dystrophy or retinal degeneration, Wolfram syndrome, recessive Wolfram syndrome, dominant Wolfram syndrome, low-frequency sensorineural hearing loss, recessive low-frequency sensorineural hearing loss, dominant low-frequency sensorineural hearing loss, ophthalmo-otitis syndrome, recessive ophthalmo-otitis syndrome, dominant ophthalmo-otitis syndrome, recessive kidney, skeletal and retinal abnormalities, recessive abetalipoproteinemia, microcephaly, recessive microcephaly, dominant microcephaly, growth disorders and retinopathy recessive microcephaly, Vietti crystalline corneal-retinal dystrophy, recessive Vietti crystalline corneal-retinal dystrophy Fee, dominant Vietti crystalline corneal-retinal dystrophy, Wagner disease, erosive vitreoretinopathy, Wagner disease and erosive vitreoretinopathy, recessive Wagner disease and erosive vitreoretinopathy, dominant Wagner disease and erosive vitreoretinopathy, febrile seizures, recessive febrile seizures, dominant febrile seizures, dominant / recessive febrile seizures, choroidal dystrophy, recessive choroidal dystrophy, dominant choroidal dystrophy, centrally ring-shaped choroidal dystrophy, dominant centrally ring-shaped choroidal dystrophy, recessive centrally ring-shaped choroidal dystrophy, epiphyseal dysplasia, recessive epiphyseal dysplasia, dominant epiphyseal dysplasia, Multiple epiphyseal dysplasia, recessive multiple epiphyseal dysplasia, dominant multiple epiphyseal dysplasia, ichthyosis, recessive ichthyosis, dominant ichthyosis, quadriplegia and delayed recessive ichthyosis, chorioretinal atrophy, bifocal chorioretinal atrophy, progressive bifocal chorioretinal atrophy, recessive progressive bifocal chorioretinal atrophy, dominant progressive bifocal chorioretinal atrophy, Refsum disease, recessive Refsum disease, dominant Refsum disease, adult-onset recessive Refsum disease, infantile recessive Refsum disease, retinal cone dystrophy, recessive retinal cone dystrophy, dominant retinal cone dystrophy, retinal cone dystrophy 1, recessive retinal cone dystrophy 1, dominant retinal cone dystrophy Type 1, Type 3 dichromacy, recessive type 3 dichromacy, dominant type 3 dichromacy, mucopolysaccharidosis, recessive mucopolysaccharidosis, dominant mucopolysaccharidosis, monochromacy Pingelap, recessive monochromacy Pingelap, dominant monochromacy Pingelap, Klippel-Vehr syndrome, recessive Klippel-Vehr syndrome, dominant Klippel-Vehr syndrome, microphthalmia, recessive microphthalmia, dominant microphthalmia, limb-girdle muscular dystrophy, recessive limb-girdle muscular dystrophy, dominant limb-girdle muscular dystrophy, short-rib thoracic dysplasia, recessive short-rib thoracic dysplasia, dominant short-rib thoracic dysplasia, polydactyly recessive short-rib thoracic dysplasia, retinal dystrophy recessive short-rib thoracic dysplasia,Intellectual disability, trunk obesity, retinal dystrophy, and micropenis (MORM) syndrome, recessive MORM syndrome, dominant MORM syndrome, spasticity and retinal degeneration recessive intellectual disability, Cockayne syndrome, recessive Cockayne syndrome, dominant Cockayne syndrome, congenital retinal detachment, recessive asymptomatic congenital retinal detachment, dominant asymptomatic congenital retinal detachment, hemolytic anemia, nonspherocytic hemolytic anemia, recessive nonspherocytic hemolytic anemia, dominant nonspherocytic hemolytic anemia, hereditary neuropathy, hereditary neuropathy (Lasse type), recessive hereditary neuropathy (Lasse type), dominant hereditary neuropathy (Lasse type) Choroidal sclerosis, recessive choroidal sclerosis, dominant choroidal sclerosis, retinopathy, recessive retinopathy, dominant retinopathy, combined dominant and recessive retinopathy, diffuse dominant retinopathy, variable dominant retinopathy, diffuse and variable dominant retinopathy, microcephaly, recessive microcephaly, dominant microcephaly, lymphedema-dominant microcephaly, chorioretinopathy-dominant microcephaly, lymphedema- and chorioretinopathy-dominant microcephaly, chorioretinopathy, recessive chorioretinopathy, dominant chorioretinopathy, chorioretinopathy and microcephaly, recessive chorioretinopathy and microcephaly, dominant chorioretinopathy and microcephaly, renal coloboma syndrome, recessive renal coloboma syndrome, dominant renal coloboma syndrome, asymptomatic dysplasia Hearing, inferior non-symptomatic hearing loss, dominant non-symptomatic hearing loss, gyroscopic atrophy, inferior gyroscopic atrophy, dominant gyroscopic atrophy, gyroscopic retinochoroidal atrophy, vitreoretinopathy, exudative vitreoretinopathy, familial exudative vitreoretinopathy, recessive familial exudative vitreoretinopathy, dominant familial exudative vitreoretinopathy, dominant familial exudative vitreoretinopathy and Coats disease, neovascular inflammatory vitreoretinopathy, recessive neovascular inflammatory vitreoretinopathy, dominant neovascular inflammatory vitreoretinopathy, focal atrophy, recessive focal atrophy, dominant focal atrophy, Meckel syndrome, recessive Meckel syndrome, dominant Meckel syndrome, vitreoretinopathy, recessive vitreoretinopathy Body-retinal choriolepidosis, dominant vitreous-retinal choriolepidosis, bethrophinosis, recessive bethrophinosis, dominant bethrophinosis, high bone mass trait, recessive high bone mass trait, dominant high bone mass trait, osteoporosis-pseudoglioma syndrome, recessive osteoporosis-pseudoglioma syndrome, dominant osteoporosis-pseudoglioma syndrome, microphthalmia, recessive microphthalmia, dominant microphthalmia, retinal disease syndrome, recessive retinal disease syndrome, dominant retinal disease syndrome, microphthalmia and retinal disease syndrome, recessive microphthalmia and retinal disease syndrome, dominant microphthalmia and retinal disease syndrome, true microphthalmia, recessive true microphthalmia, dominant true microphthalmia, osteogenesis imperfecta, recessive osteogenesis imperfecta,Dominant osteogenesis imperfecta, developmental disorders, osteoarthritis and symptomatic disorders, syringomyelia optic disc malformation, recessive syringomyelia malformation, dominant syringomyelia optic disc malformation, pitted white retina, recessive pitted white retina, dominant pitted white retina, mevalonic aciduria, recessive mevalonic aciduria, dominant mevalonic aciduria, hyper-IgD syndrome, recessive hyper-IgD syndrome, dominant hyper-IgD syndrome, spastic paraplegia, recessive spastic paraplegia, dominant spastic paraplegia, neuropathy, recessive spastic paraplegia, optic nerve atrophy, recessive spastic paraplegia, neuropathy and optic nerve atrophy, recessive spastic paraplegia (dementia), recessive dementia, dominant dementia, familial dominant dementia, retinoblastosis Tumor, recessive retinoblastoma, dominant retinoblastoma, germline retinoblastoma, somatic retinoblastoma, dominant germline or somatic retinoblastoma, retinocytoma, benign retinocytoma, pineal glandoma, osteosarcoma, rod monochromacy, recessive rod monochromacy, dominant rod monochromacy, monochromacy, recessive monochromacy, dominant monochromacy, rod monochromacy, rod recessive monochromacy, rod dominant monochromacy, recessive rod monochromacy or monochromacy, pattern dystrophy, recessive pattern dystrophy, dominant pattern dystrophy, S cone syndrome, reinforced S cone syndrome (ESC), recessive ESC, dominant ESC, Goldmann-Fabre syndrome Syndrome, recessive Goldmann-Fabre syndrome, dominant Goldmann-Fabre syndrome, bosniadystrophy, recessive bosniadystrophy, dominant bosniadystrophy, leukotritinitis, recessive leukotritinitis, dominant leukotritinitis, mucolipidosis IIIγ, recessive mucolipidosis IIIγ, dominant mucolipidosis IIIγ, Meinzer-Sardino syndrome, recessive Meinzer-Sardino syndrome, dominant Meinzer-Sardino syndrome, pseudoxanthoma elastica, recessive pseudoxanthoma elastica, dominant pseudoxanthoma elastica, Knobloch syndrome Recessive Knobloch syndrome, dominant Knobloch syndrome, foveal hypoplasia, recessive foveal hypoplasia, dominant foveal hypoplasia, anterior segment malformation, recessive anterior segment malformation, dominant anterior segment malformation, foveal hypoplasia and anterior segment malformation, recessive foveal hypoplasia and anterior segment malformation, dominant foveal hypoplasia and anterior segment malformation, spastic ataxia, recessive spastic ataxia, dominant spastic ataxia, de Grouchy syndrome, Boucher-Neuhauser syndrome, recessive Boucher-Neuhauser syndrome, dominant Boucher-Neuhauser syndrome, Boucher-Neuhauser syndrome with chorioretinal dystrophy,Recessive Boucher-Neuhauser syndrome with chorioretinal dystrophy, dominant Boucher-Neuhauser syndrome with chorioretinal dystrophy, hypoprebetalipoproteinemia, polyacanthocytosis, retinitis pigmentosa, and globus pallidus (HARP) degeneration, recessive HARP degeneration, dominant HARP degeneration, Haller-Folden-Spatz syndrome, recessive Haller-Folden-Spatz syndrome, dominant Haller-Folden-Spatz syndrome, Alagille syndrome, recessive Alagille syndrome, dominant Alagille syndrome, polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and premature cataracts PHARC (Phase-Retinal Atrophy), recessive PHARC, dominant PHARC, recessive symptomatic PHARC, Sausby's retinal degeneration, recessive Sausby's retinal degeneration, dominant Sausby's retinal degeneration, vitreoretinal dystrophy, recessive vitreoretinal dystrophy, dominant vitreoretinal dystrophy, optic neuropathy, recessive optic neuropathy, dominant optic neuropathy, late-onset dominant optic neuropathy, mouth-face-finger syndrome 1, Simpson-Goravi-Boehmel syndrome 2, X-linked retinoschisis, X-linked Oregon eye disease, X-linked optic nerve atrophy, retinal dysplasia, recessive retinal dysplasia, dominant retinal dysplasia, X-linked retinal dysplasia, primary X-linked retinal Dysplasia, X-linked Norie disease, Coats disease, X-linked Åland Island eye disease, autoimmune inner ear disease (AIED), AIED-like disease, colloideremia, X-linked colloideremia, neuropathy, optic atrophy, hearing loss and retinitis pigmentosa, X-linked neuropathy, optic atrophy, hearing loss and retinitis pigmentosa, X-linked blue cone monochromacy, X-linked type 1 trichromacy and rare macular dystrophy in blue cone monochromacy (BCM), X-linked type 2 trichromacy and rare macular dystrophy in blue cone monochromacy (BCM), mitochondrial Kearns-Sey syndrome including retinitis pigmentosa Aar syndrome, Leigh syndrome, retinopathy, mitochondrial pigmentary retinopathy and sensorineural hearing loss, albinism, oculocutaneous albinism, neuronal ceroid lipofuscinosis, Zellweger spectrum disorder, cobalamin C deficiency, blue cone monochromacy, hereditary red-green color blindness, type 3 color blindness and yellow-blue color blindness, strepoptic vision, delayed cone adaptation, uveitis, diabetic retinopathy, diabetic macular edema, persistent corneal epithelial defect, neurotrophic keratitis, herpes interstitial keratitis, chronic dry eye, glaucoma, ocular detachment, ocular blister formation, ocular scarring, visual loss, blindness, corneal blindness, dry eye disease, tear-deficient dry eye disease.Sjögren's syndrome-related tear-deficient dry eye disease, non-Sjögren's syndrome-related dry eye disease, evaporative dry eye disease, meibomian gland dysfunction, blepharitis, blepharitis, ocular rosacea and atopic dermatitis, tear-deficient and evaporative dry eye diseases, Fuchs dystrophy, Fuchs corneal endothelial dystrophy (FECD), Fuchs endothelial dystrophy (FED), panuveitis, diffuse uveitis, panuveitis, cataract, partial cataract, complete cataract, secular cataract, progressive cataract, hard cataract, soft cataract, nuclear cataract, nuclear sclerosis cataract, cortical cataract, posterior subcapsular cataract Cataracts, congenital cataracts, corneal dystrophy, epithelial and subepithelial dystrophy, epithelial basement membrane dystrophy, epithelial recurrent erosive dystrophy (Franschetti corneal dystrophy, Dystrophia smolandiensis, and / or Dystrophia helsinglandica), subepithelial mucinous corneal dystrophy, Miesmann corneal dystrophy, Risch epithelial corneal dystrophy, gelatinous drop-like corneal dystrophy, Bowman's layer dystrophy, Reiss-Bücklers corneal dystrophy, Thiel-Benkhe corneal dystrophy, stromal dystrophy Fie-TGFB1 corneal dystrophy, lattice corneal dystrophy, type 1 variant of lattice corneal dystrophy (III, IIIA, I / IIIA, IV), granular corneal dystrophy type 1, granular corneal dystrophy type 2, stromal dystrophy, maculoplasty, Schneider crystalline corneal dystrophy, congenital stromal corneal dystrophy, Fleck's dystrophy, posterior amorphous corneal dystrophy, François central cloud dystrophy, pre-Descemet's corneal dystrophy, endothelial dystrophy, Fuchs' dystrophy, posterior polymorphism Corneal dystrophy, congenital hereditary endothelial dystrophy, X-linked corneal endothelial dystrophy, superficial dystrophy, epithelial basement membrane dystrophy, Miesmann's juvenile corneal epithelial dystrophy, gelatinous drop-like corneal dystrophy, Risch epithelial corneal dystrophy, subepithelial mucinous corneal dystrophy, Reiss-Bücklers corneal dystrophy, Thiel-Benkhe dystrophy, stromal dystrophy, lattice corneal dystrophy, granular corneal dystrophy, maculoplasty, Schneider crystalline corneal dystrophy, congenital stromal corneal dystrophy,It can be used in the treatment of Fleck's dystrophy, posterior dystrophy, Fuchs' dystrophy, posterior polymorphic corneal dystrophy, congenital hereditary endothelial dystrophy, keratopathy, keratopathy zolia, corneal keratopathy zolia, and / or calcific keratopathy zolia.

[0117] In some embodiments, one or more transgenes include genes expressed in the photoreceptor of interest.

[0118] In some embodiments, the disease or condition is Stargardt disease. In some embodiments, one or more symptoms include central visual field loss that develops in childhood or early adolescence. In some embodiments, the disease or condition is autosomal recessive. In some embodiments, the disease or condition is associated with one or more mutations in ABCA4. In some embodiments, the disease or condition has a prevalence of about 1 in 10,000 people. Mutations in ABCA4 also cause cone-rod dystrophy (loss of visual clarity, photophobia, color blindness), which is also autosomal recessive and worsens over time. In some embodiments, the disease or condition is associated with one or more mutations in ELOVL4. For example, Stargardt disease can also be caused, less frequently, by mutations in the ELOVL4 gene.

[0119] In some embodiments, the disease or condition is retinitis pigmentosa. In some embodiments, one or more symptoms include a wide range of severity and, depending on the mutation, may develop in childhood or late adulthood. In some embodiments, one or more symptoms include night blindness, peripheral vision loss, and / or symptoms that eventually affect the central vision. In some embodiments, the disease or condition is caused by one or more gene mutations. In some embodiments, the disease or condition is associated with about 60 gene mutations. In some embodiments, the disease or condition is associated with an autosomal dominant mutation in RHO, which may account for about 20–30% of cases. In some embodiments, the disease or condition is associated with an autosomal recessive mutation in USH2A (Usher syndrome type II), which may account for about 10–15% of cases and may have a prevalence of about 4 in 100,000 people. In some embodiments, one or more symptoms develop in late adolescence / early adulthood. In some embodiments, the disease or condition has a prevalence of about 1 in 4,000 people.

[0120] In some embodiments, one or more transgenes include genes that are expressed in the target retinal pigment epithelial (RPE) cells.

[0121] In some embodiments, the disease or condition is Leber's congenital amaurosis (LCA). In some embodiments, one or more symptoms include severe visual impairment that develops in infancy. In some embodiments, the disease or condition is autosomal recessive. In some embodiments, the disease or condition has a prevalence of about 2 in 100,000 people. In some embodiments, the disease or condition is associated with one or more mutations in RPE65 and / or CEP290. Other major gene mutation populations are genes that are expressed primarily in photoreceptors rather than in RPE cells.

[0122] In some embodiments, the disease or condition is characterized by white punctate retina. In some embodiments, one or more symptoms include night blindness and delayed dark adaptation. In some embodiments, the disease or condition is autosomal recessive. In some embodiments, the disease or condition is a type of congenital arresting night blindness. In some embodiments, the disease or condition involves one or more mutations in the RDH5 gene in RPE cells.

[0123] In some embodiments, the disease or condition is white spot retinitis. In some embodiments, one or more symptoms may develop in childhood and may include night blindness. In some embodiments, the disease or condition is autosomal recessive. In some embodiments, the disease or condition develops in about 1% of patients with autosomal recessive RCD (1 in 800,000 individuals worldwide). In some embodiments, the disease or condition is associated with one or more mutations in RLBP1.

[0124] In some embodiments, the disease or condition is hereditary retinal dystrophy (IRD). In some embodiments, the disease or condition is IRD caused by one or more MERTK receptor mutations. In some embodiments, the disease or condition is autosomal recessive. In some embodiments, the disease or condition is hereditary retinal dystrophy (IRD), affecting about 2% of patients, and IRD has a prevalence of about 1 in 2000 people.

[0125] In some aspects, the disease or condition or its symptoms may include one or more of the following: Stargardt disease; Leber congenital amaurosis; early-onset severe retinal dystrophy; retinitis pigmentosa; asymptomatic retinitis pigmentosa; Usher syndrome types 1-3; Vietti crystalline corneal retinal dystrophy; congenital stasis nyctina; punctate fundus; punctate retinitis; choroideremia; monochromacy; retinal manifestation of Alström syndrome; Valday-Biedl syndrome; Joubert syndrome; cerebral gyroretinal atrophy; X-linked congenital retinoschisis; progressive bifocal chorioretinal atrophy; retinoblastoma; uveitis; diabetic retinopathy; diabetic macular edema; persistent corneal epithelial defects; neurotrophic keratitis; chronic dry eye; wet AMD; dry AMD; geographic atopic dermatitis; and glaucoma.

[0126] In some embodiments, compositions, methods, and uses for gene therapy of ocular disorders are provided herein. In some embodiments, recombinant HSV genome or HSV can be used for topical administration.

[0127] VI. Method A particular aspect of this disclosure relates to a method for delivering polypeptides to one or more cells of a target (e.g., one or more cells of the eye, e.g., anterior chamber; posterior chamber; ciliary body; corneal epithelial cells; rod cells; cone cells; photoreceptors; retinal pigment epithelial cells; retinal ganglion cells; bipolar cells; horizontal cells; Müller cells; axonal cells; etc.), comprising administering a pharmaceutical composition to a target comprising one or more recombinant nucleic acids described herein that comprise one or more polynucleotides encoding a polypeptide (e.g., recombinant herpes simplex virus genomes such as recombinant HSV-1 genome) and a pharmaceutically acceptable carrier. In some embodiments, the pharmaceutical composition is administered to a subject by injection, by injection into the eye, by subretinal injection, by intraocular injection, by intravitreous injection, by suprachoroidal injection, by intrachorionic injection, intraocular, intravitreous, topically, subcutaneously, subconjunctivally, subtenon's capsule, intrachorionically, retroocularly, systemically, parenterally, periocularly, near the sclera, near the anterior sclera, near the posterior sclera, orally, periocularly, or onto the choroid. In some embodiments, the herpesvirus or pharmaceutical composition is administered using eye drops, ointments, pastes, creams, suspensions, emulsions, fatty ointments, gels, bioadhesive gels, powders, lotions, solutions, or sprays. In some embodiments, the herpesvirus (e.g., herpes simplex virus) is replication-capable. In some embodiments, the herpesvirus (e.g., herpes simplex virus) is replication-deficient. In some aspects, herpesviruses (e.g., herpes simplex virus) are not oncolytic.

[0128] In some embodiments, the subject is human. In some embodiments, the subject has an eye condition or disease. In some embodiments, the eye condition or disease is retinitis pigmentosa, recessive retinitis pigmentosa, severe recessive retinitis pigmentosa, dominant retinitis pigmentosa, dominant retinitis pigmentosa with choroidal lesions, recessive retinitis pigmentosa with paraarteriolar preservation of RPE (PPRPE), recessive retinitis pigmentosa with posterior column ataxia (PCARP), recessive retinitis pigmentosa with microcytosis, symptomatic recessive retinitis pigmentosa, recessive symptomatic disease with retinitis pigmentosa, non-symptomatic recessive retinitis pigmentosa, non-symptomatic dominant retinitis pigmentosa, symptomatic dominant retinitis pigmentosa, juvenile recessive retinitis pigmentosa, recessive retinitis pigmentosa and intellectual disability, recessive retinitis pigmentosa with macular degeneration, severe early-onset recessive retinitis pigmentosa, recessive retinitis pigmentosa and bone malformations, recessive retinitis pigmentosa and skeletal abnormalities, dominant retinitis pigmentosa with sensorineural hearing loss, recessive retinitis pigmentosa with hearing loss, recessive retinitis pigmentosa with hearing loss and additional disability, recessive retinitis pigmentosa with vitreous degeneration, early-onset recessive retinitis pigmentosa with macular defect, X-linked retinitis pigmentosa, recessive X-linked retinitis pigmentosa, dominant X-linked retinitis pigmentosa, severe X-linked retinitis pigmentosa, X-linked retinitis pigmentosa with intellectual disability, myopathy X-linked retinitis pigmentosa with -, Valday-Beedl-like retinitis pigmentosa, Valday-Beedl-like recessive retinitis pigmentosa, bigenic retinitis pigmentosa, bigenic retinitis pigmentosa with retinal outer segment membrane protein 1, bigenic retinitis pigmentosa with PRPH2, recessive retinitis pigmentosa with early macular lesions, recessive hearing loss without retinitis pigmentosa, recessive congenital hearing loss without retinitis pigmentosa, recessive retinitis pigmentosa and recessive ataxia, recessive retinitis pigmentosa and dominant ataxia, mitochondrial retinitis pigmentosa, mitochondrial retina with developmental and neurological abnormalities Pigmentous degeneration, mitochondrial retinitis pigmentosa with progressive sensorineural hearing loss, mitochondrial retinitis pigmentosa with hearing loss and neurological abnormalities, autosomal dominant retinitis pigmentosa, asymptomatic autosomal dominant retinitis pigmentosa, autosomal recessive retinitis pigmentosa, asymptomatic autosomal recessive retinitis pigmentosa, retinal pigment epithelium (RPE), recessive RPE, dominant RPE, recessive RPE degeneration, dominant RPE degeneration, ataxia, recessive ataxia, dominant ataxia, Senior-Loken syndrome, recessive Senior-Loken syndrome, dominant Senior-Loken syndrome, nephronoplasia, recessive nephronoplasia, dominant nephronoplasia,Adolescent recessive nephronoplasia, ciliopathy-associated recessive nephronoplasia, juvenile nephronoplasia, juvenile recessive nephronoplasia, juvenile dominant nephronoplasia, Usher syndrome, Usher syndrome type I, Usher syndrome type II, Usher syndrome type III, recessive Usher syndrome, atypical recessive Usher syndrome, dominant Usher syndrome, type 2 recessive Usher syndrome, type 2a recessive Usher syndrome, type 3 recessive Usher syndrome, type 3-like recessive Usher syndrome, atypical recessive Usher syndrome, type 1 recessive Usher syndrome, type 1b recessive Usher syndrome, type 1d recessive Usher syndrome, type 1f recessive Usher syndrome, 1J recessive Usher syndrome, 1k recessive Usher syndrome, bigenic Usher syndrome with CDH23, bigenic Usher syndrome with PCDH15, Acadian recessive Usher syndrome, recessive atypical Usher syndrome (USH3-like), Leber's congenital amaurosis, recessive Leber's congenital amaurosis, dominant Leber's congenital amaurosis, de novo Leber's congenital amaurosis, dominant Leber's congenital amaurosis and pituitary dysfunction, recessive Leber's congenital amaurosis with myopathy, recessive Leber's congenital amaurosis with severe childhood retinal dystrophy, mitochondrial Ndoria-type Leber hereditary optic neuropathy, Leber hereditary optic neuropathy, optic atrophy, recessive optic atrophy, dominant optic atrophy, optic atrophy with ataxia, recessive optic atrophy with ataxia, dominant optic atrophy with ataxia, recessive optic atrophy with ataxia and 3-methylglutaconic aciduria, cataract, dominant optic atrophy with ataxia and anreflexia, Kaer-type dominant optic atrophy, dominant optic atrophy with sensorineural hearing loss, recessive cerebellar degeneration with optic atrophy, optic atrophy with anesthesia-dystonia syndrome, X-linked optic atrophy with anesthesia-dystonia syndrome, retinal dystrophy, recessive Dominant retinal dystrophy, hereditary retinal dystrophy, early-onset recessive retinal dystrophy, recessive symptomatic retinal dystrophy, recessive asymptomatic retinal dystrophy, recessive symptomatic and asymptomatic retinal dystrophy, recessive optic atrophy and retinal dystrophy, recessive retinal dystrophy and obesity, recessive retinal dystrophy and cerebellar dysplasia, symptomatic recessive optic atrophy and retinal dystrophy, dominant retinal dystrophy with iris defects, ciliopathy spectrum including retinal dystrophy, recessive ciliopathy spectrum including retinal dystrophy,Dominant ciliopathies spectrum including retinal dystrophy, dominant optic atrophy with neuropathy and myopathy, dominant optic atrophy with intellectual disability and developmental delay, symptomatic optic atrophy, asymptomatic optic atrophy, recessive asymptomatic optic atrophy, dominant asymptomatic optic atrophy, recessive symptomatic optic atrophy, dominant symptomatic optic atrophy, Charcot-Marie-Tooth disease, recessive Charcot-Marie-Tooth disease, dominant Charcot-Marie-Tooth disease, benign spotted retina, recessive benign spotted retina, dominant benign spotted retina, symptomatic retinopathy, recessive symptomatic retinopathy, dominant symptomatic retinopathy, Batten disease, recessive Batten Batten disease, dominant Batten disease, recessive Batten disease (neuroceroid lipofuscinosis type 3), juvenile recessive Batten disease (neuroceroid lipofuscinosis type 3), neuroceroid lipofuscinosis, recessive neuroceroid lipofuscinosis, recessive neuroceroid lipofuscinosis type 1, dominant neuroceroid lipofuscinosis, Stargart disease, recessive Stargart disease, dominant Stargart disease, juvenile Stargart disease, late-onset Stargart disease, Stargart-like macular dystrophy, recessive Stargart-like macular dystrophy, dominant Stargart-like macular dystrophy, macular dystrophy Rophy, recessive macular dystrophy, early-onset macular dystrophy, adult-onset macular dystrophy, early-onset recessive macular dystrophy, adult-onset recessive macular dystrophy, early adult-onset recessive macular dystrophy, juvenile recessive macular dystrophy with hypotrichosis, dominant macular dystrophy, late-onset dominant macular dystrophy, dominant macular dystrophy with lens zonules, bullseye dominant macular dystrophy, butterfly-shaped dominant macular dystrophy, age-related dominant macular dystrophy, benign concentric annular dominant macular dystrophy, vitelloid recessive macular dystrophy, vitelloid dominant macular dystrophy Stroke, atypical vitelloid-dominant macular dystrophy, dominant adult-type vitelloid-dominant macular dystrophy, Stargard-type dominant macular dystrophy, Stargard-type dominant macular dystrophy, North Carolina-dominant macular dystrophy, North Carolina-like dominant macular dystrophy, North Carolina-like dominant macular dystrophy with progressive sensorineural hearing loss, cystic-type dominant macular dystrophy, Best-type dominant macular dystrophy, occult macular dystrophy, recessive occult macular dystrophy, dominant occult macular dystrophy, age-related familial macular dystrophy,X-linked atrophic macular dystrophy, recessive X-linked atrophic macular dystrophy, dominant X-linked atrophic macular dystrophy, mitochondrial macular pattern dystrophy with type II diabetes and hearing loss, macular fundus, recessive macular fundus, dominant macular fundus, rod dystrophy, recessive rod dystrophy, dominant rod dystrophy, cone dystrophy, recessive cone dystrophy, dominant cone dystrophy, recessive cone dystrophy with supernormal rod electroretinogram, early-onset recessive cone dystrophy, late-onset recessive cone dystrophy, cone dystrophy 1, X-linked Chain-linked pyramidal dystrophy 1, pyramidal dystrophy 2, progressive pyramidal dystrophy 2, X-linked progressive pyramidal dystrophy 2, delayed pyramidal adaptation, recessive delayed pyramidal adaptation, dominant delayed pyramidal adaptation, pyramidal-rod dystrophy, recessive pyramidal-rod dystrophy, dominant pyramidal-rod dystrophy, isolated pyramidal-rod dystrophy, progressive pyramidal-rod dystrophy, X-linked pyramidal-rod dystrophy, X-linked progressive pyramidal-rod dystrophy, progressive dominant pyramidal-rod dystrophy, pyramidal-rod dystrophy and enamel hypoplasia syndrome, recessive pyramidal-rod dystrophy and Enamel hypoplasia syndrome, dominant cone-rod dystrophy and enamel hypoplasia syndrome, recessive cone-rod dystrophy with internal retinopathy, recessive cone-rod dystrophy with bone disease, congenital symptomatic non-progressive recessive cone-rod dystrophy, recessive cone-rod dystrophy with hearing loss, recessive cone-rod dystrophy with psychomotor retardation, recessive cone and cone-rod dystrophy, cone-rod synapse disease, congenital cone-rod synapse disease, recessive congenital cone-rod synapse disease, dominant congenital cone-rod synapse disease, rod-cone dystrophy, recessive rod-cone dystrophy Dominant rod-cone dystrophy, early-onset recessive rod-cone dystrophy, non-symptomatic recessive rod-cone dystrophy, recessive Newfoundland rod-cone dystrophy, recessive progressive cone dystrophy, Stickler syndrome, dominant Stickler syndrome, recessive Stickler syndrome, dominant Stickler syndrome type I, dominant Stickler syndrome type II, Marshall syndrome, dominant Marshall syndrome, recessive Marshall syndrome, monochromacy, recessive monochromacy, dominant monochromacy, recessive complete monochromacy, recessive incomplete monochromacy, macular degeneration, age-related macular degeneration, complex etiology age-related macular degeneration.Solitary age-related macular degeneration, wet age-related macular degeneration, dry age-related macular degeneration, drusen, recessive drusen, dominant drusen, early-onset recessive drusen, early-onset dominant drusen, macular drusen, dominant radial macular drusen, pigmentary paravenous chorioretinal atrophy, recessive pigmentary paravenous chorioretinal atrophy, dominant pigmentary paravenous chorioretinal atrophy, progressive bifocal chorioretinal atrophy, Valday-Beedl syndrome, recessive Valday-Beedl syndrome, dominant Valday-Beedl syndrome, recessive Valday-Beedl syndrome with developmental abnormalities, retinal degeneration, recessive retinal degeneration, dominant retinal degeneration, non-symptomatic recessive retinal degeneration, Doynn's honeycomb retinal degeneration, Doynn's recessive honeycomb retinal degeneration, Doynn's dominant honeycomb retinal degeneration (Malattiya) Reventinese, recessive nephronoplasia with retinal degeneration, Alström syndrome, recessive Alström syndrome, dominant Alström syndrome, Joubert syndrome, recessive Joubert syndrome, dominant Joubert syndrome, Joubert syndrome, recessive Joubert syndrome, dominant Joubert syndrome, X-linked Joubert syndrome, vitreoretinal degeneration, recessive vitreoretinal degeneration, dominant vitreoretinal degeneration, snowflake vitreoretinal degeneration Vitreous retinal degeneration, snowflake dominant vitreoretinal degeneration, small mouth disease, recessive small mouth disease, dominant small mouth disease, night blindness, stop night blindness, congenital night blindness, congenital stop night blindness, severe congenital stop night blindness, recessive congenital stop night blindness, Recessive complete congenital stop night blindness, dominant congenital stop night blindness, Nougarette type dominant congenital stop night blindness, small-mouth type recessive congenital stop night blindness, Riggs type recessive congenital stop night blindness, Schubert-Bornschein type Recessive congenital pycnophobia, pitted retinal recessive congenital pycnophobia, complete recessive congenital pycnophobia, X-linked congenital pycnophobia, incomplete X-linked congenital pycnophobia, retinal vascular disease, cerebral leukodystrophy, retinal vascular disease with cerebral leukodystrophy, recessive retinal vascular disease with cerebral leukodystrophy, dominant retinal vascular disease with cerebral leukodystrophy, Eicardi-Goutier syndrome, Eicardi-Goutier syndrome 1, recessive Eicardi-Goutier syndrome 1, dominant Eicardi-Goutier syndrome 1, lupus frostbite, recessive lupus frostbite, dominant lupus frostbite, Martinique retinal dystrophy and retinitis pigmentosa, recessive Martinique retinal dystrophy and retinitis pigmentosa, dominant Martinique retinal dystrophy and retinitis pigmentosa, spinocerebellar ataxia, recessive spinocerebellar ataxia,Dominant spinocerebellar ataxia, spinocerebellar ataxia with macular dystrophy, spinocerebellar ataxia with retinal degeneration, spinocerebellar ataxia with macular dystrophy or retinal degeneration, recessive spinocerebellar ataxia with macular dystrophy or retinal degeneration, dominant spinocerebellar ataxia with macular dystrophy or retinal degeneration, Wolfram syndrome, recessive Wolfram syndrome, dominant Wolfram syndrome, low-frequency sensorineural hearing loss, recessive low-frequency sensorineural hearing loss, dominant low-frequency sensorineural hearing loss, ophthalmo-otitis syndrome, recessive ophthalmo-otitis syndrome, dominant ophthalmo-otitis syndrome, recessive kidney, skeletal and retinal abnormalities, recessive abetalipoproteinemia, microcephaly, recessive microcephaly, dominant microcephaly, growth disorders and retinopathy recessive microcephaly, Vietti crystalline corneal-retinal dystrophy, recessive Vietti crystalline corneal-retinal dystrophy, dominant Vietti crystalline corneal-retinal dystrophy, Wagner's disease, erosive vitreoretinopathy, Wagner's disease and erosive vitreoretinopathy, recessive Wagner's disease Erosive vitreoretinopathy, dominant Wagner disease and erosive vitreoretinopathy, febrile seizures, recessive febrile seizures, dominant febrile seizures, dominant / recessive febrile seizures, choroidal dystrophy, recessive choroidal dystrophy, dominant choroidal dystrophy, central corticochoroidal dystrophy, dominant central corticochoroidal dystrophy, recessive central corticochoroidal dystrophy, epiphyseal dysplasia, recessive epiphyseal dysplasia, dominant epiphyseal dysplasia, multiple epiphyseal dysplasia, recessive multiple epiphyseal dysplasia, dominant multiple epiphyseal dysplasia, ichthyosis, recessive ichthyosis, dominant ichthyosis, quadriplegia and delayed recessive ichthyosis, chorioretinal atrophy Retinal atrophy, bifocal chorioretinal atrophy, progressive bifocal chorioretinal atrophy, recessive progressive bifocal chorioretinal atrophy, dominant progressive bifocal chorioretinal atrophy, Refsum disease, recessive Refsum disease, dominant Refsum disease, adult-type recessive Refsum disease, infant-type recessive Refsum disease, retinal cone dystrophy, recessive retinal cone dystrophy, dominant retinal cone dystrophy, retinal cone dystrophy 1, recessive retinal cone dystrophy 1, dominant retinal cone dystrophy 1, type 3 dichromacy, recessive type 3 dichromacy, dominant type 3 dichromacy, mucopolysaccharidosis, recessive mucopolysaccharidosis, dominant mucopolysaccharidosis, monochromacy Pingelap, recessive monochromacy Pingelap, dominant Monochromacy Pingelap, Klippel-Veil syndrome, recessive Klippel-Veil syndrome, dominant Klippel-Veil syndrome, microphthalmia, recessive microphthalmia, dominant microphthalmia, limb-girdle muscular dystrophy, recessive limb-girdle muscular dystrophy, dominant limb-girdle muscular dystrophy, short-rib thoracic dysplasia, recessive short-rib thoracic dysplasia, dominant short-rib thoracic dysplasia, polydactyly recessive short-rib thoracic dysplasia, retinal dystrophy recessive short-rib thoracic dysplasia, intellectual disability, trunk obesity, retinal dystrophy, and micropenis (MORM) syndrome, recessive MORM syndrome, dominant MORM syndrome, spasticity and retinal degeneration recessive intellectual disability.Cockayne syndrome, recessive Cockayne syndrome, dominant Cockayne syndrome, congenital retinal detachment, recessive asymptomatic congenital retinal detachment, dominant asymptomatic congenital retinal detachment, hemolytic anemia, nonspherocytic hemolytic anemia, recessive nonspherocytic hemolytic anemia, dominant nonspherocytic hemolytic anemia, hereditary neuropathy, hereditary neuropathy (Lasse type), recessive hereditary neuropathy (Lasse type), dominant hereditary neuropathy (Lasse type), choroidal sclerosis, recessive choroidal sclerosis, dominant choroidal sclerosis, retinopathy, recessive retinopathy, dominant retinopathy, combined dominant and recessive retinopathy, diffuse dominant retinopathy, variable dominant retinopathies Membrane disease, diffuse and variable dominant retinopathy, microcephaly, recessive microcephaly, dominant microcephaly, lymphedema dominant microcephaly, chorioretinopathy dominant microcephaly, lymphedema and chorioretinopathy dominant microcephaly, chorioretinopathy, recessive chorioretinopathy, dominant chorioretinopathy, chorioretinopathy and microcephaly, recessive chorioretinopathy and microcephaly, dominant chorioretinopathy and microcephaly, renal coloboma syndrome, recessive renal coloboma syndrome, dominant renal coloboma syndrome, asymptomatic hearing loss, recessive asymptomatic hearing loss, dominant asymptomatic hearing loss, gyroretinopathy, recessive gyroretinopathy, dominant gyroretinopathy, gyroretinal choroidal atrophy, vitreoretinopathy, exudative vitreoretinopathy Familial exudative vitreoretinopathy, recessive familial exudative vitreoretinopathy, dominant familial exudative vitreoretinopathy, dominant familial exudative vitreoretinopathy and Coats disease, neovascular inflammatory vitreoretinopathy, recessive neovascular inflammatory vitreoretinopathy, dominant neovascular inflammatory vitreoretinopathy, focal atrophy, recessive focal atrophy, dominant focal atrophy, Meckel syndrome, recessive Meckel syndrome, dominant Meckel syndrome, vitreoretinopathy, recessive vitreoretinopathy, dominant vitreoretinopathy, bestrofinosis, recessive bestrofinosis, dominant bestrofinosis, high bone mass trait, recessive high bone mass trait, dominant high bone mass trait, osteoporosis - Pseudoglioma syndrome, recessive osteoporosis-pseudoglioma syndrome, dominant osteoporosis-pseudoglioma syndrome, microphthalmia, recessive microphthalmia, dominant microphthalmia, retinal disease syndrome, recessive retinal disease syndrome, dominant retinal disease syndrome, microphthalmia and retinal disease syndrome, recessive microphthalmia and retinal disease syndrome, dominant microphthalmia and retinal disease syndrome, true microphthalmia, recessive true microphthalmia, dominant true microphthalmia, osteogenesis imperfecta, recessive osteogenesis imperfecta, dominant osteogenesis imperfecta, developmental disorders, osteoarthritis and symptomatic disorders, caudal optic disc malformation, recessive caudal optic disc malformation, dominant caudal optic disc malformation, white punctate fundus, recessive white punctate fundus,Dominant white pitted fundus, mevalonic aciduria, recessive mevalonic aciduria, dominant mevalonic aciduria, hyper IgD syndrome, recessive hyper IgD syndrome, dominant hyper IgD syndrome, spastic paraplegia, recessive spastic paraplegia, dominant spastic paraplegia, neuropathy, recessive spastic paraplegia, optic nerve atrophy, recessive spastic paraplegia, neuropathy and optic nerve atrophy, recessive spastic paraplegia (dementia), recessive dementia, dominant dementia, familial dominant dementia, retinoblastoma, recessive retinoblastoma, dominant retinoblastoma, germline retinoblastoma, somatic retinoblastoma, dominant germline or somatic retinoblastoma, retinoblastoma, benign retinoblastoma, pineal glandoma Osteosarcoma, rod monochromacy, recessive rod monochromacy, dominant rod monochromacy, monochromacy, recessive monochromacy, dominant monochromacy, rod monochromacy, rod recessive monochromacy, rod dominant monochromacy, recessive rod monochromacy or monochromacy, pattern dystrophy, recessive pattern dystrophy, dominant pattern dystrophy, S cone syndrome, reinforced S cone syndrome (ESC), recessive ESC, dominant ESC, Goldmann-Fabre syndrome, recessive Goldmann-Fabre syndrome, dominant Goldmann-Fabre syndrome, Bosniadystrophy, recessive Bosniadystrophy, dominant Bosniadystrophy, white pitted reticularis Retinitis, recessive leukotritinitis, dominant leukotritinitis, mucolipidosis IIIγ, recessive mucolipidosis IIIγ, dominant mucolipidosis IIIγ, Meinzer-Sardino syndrome, recessive Meinzer-Sardino syndrome, dominant Meinzer-Sardino syndrome, pseudoxanthoma elastica, recessive pseudoxanthoma elastica, dominant pseudoxanthoma elastica, Knobloch syndrome, recessive Knobloch syndrome, dominant Knobloch syndrome, foveal hypoplasia, recessive foveal hypoplasia, dominant foveal hypoplasia, anterior segment malformation, recessive anterior segment malformation, dominant anterior segment malformation, foveal hypoplasia and anterior eye Partial malformation, recessive foveal hypoplasia and anterior segment malformation, dominant foveal hypoplasia and anterior segment malformation, spastic ataxia, recessive spastic ataxia, dominant spastic ataxia, de Grouchy syndrome, Boucher-Neuhauser syndrome, recessive Boucher-Neuhauser syndrome, dominant Boucher-Neuhauser syndrome, Boucher-Neuhauser syndrome with chorioretinal dystrophy, recessive Boucher-Neuhauser syndrome with chorioretinal dystrophy, dominant Boucher-Neuhauser syndrome with chorioretinal dystrophy, hypoprebetalipoproteinemia, acanthocyanosis, retinitis pigmentosa,and globus pallidus (HARP) degeneration, recessive HARP degeneration, dominant HARP degeneration, Haller-Folden-Spatz syndrome, recessive Haller-Folden-Spatz syndrome, dominant Haller-Folden-Spatz syndrome, Alagille syndrome, recessive Alagille syndrome, dominant Alagille syndrome, polyneuropathy, hearing loss, ataxia, retinitis pigmentosa and early-onset cataract (PHARC), recessive PHARC, dominant PHARC, recessive symptomatic PHARC, Sausby's retinal degeneration, recessive Sausby's retinal degeneration, dominant Sausby's retinal degeneration, vitreoretinal dystrophy, recessive vitre Somatic retinal dystrophy, dominant vitreoretinal dystrophy, optic neuropathy, recessive optic neuropathy, dominant optic neuropathy, late-onset dominant optic neuropathy, mouth-face-finger syndrome 1, Simpson-Goravi-Boehmel syndrome 2, X-linked retinoschisis, X-linked Oregon eye disease, X-linked optic atrophy, retinal dysplasia, recessive retinal dysplasia, dominant retinal dysplasia, X-linked retinal dysplasia, primary X-linked retinal dysplasia, X-linked Norie disease, Coats disease, X-linked Orlando Island eye disease, autoimmune cochlear disease (AIED), AIED-like disease, colloideremia, X-linked colloideremia, neuropathy, optic atrophy Hearing loss and retinitis pigmentosa, X-linked neuropathy, optic nerve atrophy, hearing loss and retinitis pigmentosa, X-linked blue cone monochromacy, X-linked type 1 trichromacy and rare macular dystrophy in blue cone monochromacy (BCM), X-linked type 2 trichromacy and rare macular dystrophy in blue cone monochromacy (BCM), mitochondrial Kearns-Sayer syndrome including retinitis pigmentosa, Leigh syndrome, retinopathy, mitochondrial pigmentary retinopathy and sensorineural hearing loss, albinism, oculocutaneous albinism, neuronal ceroid lipofuscinosis, Zellweger spectrum disorder, cobalamin C deficiency , blue cone monochromacy, hereditary red-green color blindness, type 3 color blindness and yellow-blue color blindness, tardive vision, delayed cone adaptation, uveitis, diabetic retinopathy, diabetic macular edema, persistent corneal epithelial defect, neurotrophic keratitis, herpes interstitial keratitis, chronic dry eye, glaucoma, ocular detachment, ocular blister formation, ocular scarring, visual loss, blindness, corneal blindness, dry eye disease, tear-deficient dry eye disease, Sjögren's syndrome-related tear-deficient dry eye disease, non-Sjögren's syndrome-related dry eye disease, evaporative dry eye disease, meibomian gland dysfunction, blepharitis, blepharitis, ocular rosacea and atopic dermatitis,Tear-deficient and evaporative dry eye diseases, Fuchs dystrophy, Fuchs corneal endothelial dystrophy (FECD), Fuchs endothelial dystrophy (FED), panuveitis, diffuse uveitis, panuveitis, cataract, partial cataract, complete cataract, absent cataract, progressive cataract, hard cataract, soft cataract, nuclear cataract, nuclear sclerosis cataract, cortical cataract, posterior subcapsular cataract, congenital cataract, corneal dystrophy, epithelial and subepithelial dystrophy, epithelial basement membrane dystrophy, epithelial recurrent erosive dystrophy (Franschetti corneal dystrophy, dyst Lorphia smolandiensis and / or Dystrophia helsinglandica), subepithelial mucinous corneal dystrophy, Miesmann corneal dystrophy, Risch epithelial corneal dystrophy, gelatinous drop-like corneal dystrophy, Bowman layer dystrophy, Reiss-Bücklers corneal dystrophy, Thiel-Benkhe corneal dystrophy, stromal dystrophy-TGFB1 corneal dystrophy, lattice corneal dystrophy, type 1 variant of lattice corneal dystrophy (III, IIIA, I / IIIA, IV), granular corneal dystrophy type 1 Granular corneal dystrophy type 2, stromal dystrophy, maculoplasty, Schneider crystalline corneal dystrophy, congenital stromal corneal dystrophy, Fleck's dystrophy, posterior amorphous corneal dystrophy, François central cloud dystrophy, predescemet's membrane corneal dystrophy, endothelial dystrophy, Fuchs dystrophy, posterior polymorphic corneal dystrophy, congenital hereditary endothelial dystrophy, X-linked corneal endothelial dystrophy, superficial dystrophy, epithelial basement membrane dystrophy, Miesmann's juvenile corneal epithelial dystrophy, Gelatinous drop-type corneal dystrophy, Risch epithelial corneal dystrophy, subepithelial mucinous corneal dystrophy, Reiss-Bücklers corneal dystrophy, Thiel-Benkhe dystrophy, stromal dystrophy, lattice corneal dystrophy, granular corneal dystrophy, maculoid corneal dystrophy, Schneider crystalline corneal dystrophy, congenital stromal corneal dystrophy, Fleck's dystrophy, posterior dystrophy, Fuchs dystrophy, posterior polymorphic corneal dystrophy, congenital hereditary endothelial dystrophy, keratopathy, keratopathy, corneal keratopathy,The subjects are selected from a group consisting of calcific keratopathy and other conditions. In some embodiments, the subjects have Stargardt disease. In some embodiments, the subjects have neurotrophic keratitis. In some embodiments, the subjects have Leber's congenital amaurosis.

[0129] In some embodiments, administration of recombinant nucleic acids, viruses, pharmaceuticals and / or pharmaceutical compositions or formulations to a subject increases polypeptide levels (transcript or protein levels) in one or more contacted or treated cells of the subject by at least about twofold compared to the endogenous levels of polypeptides in one or more corresponding untreated cells of the subject. For example, administration of recombinant nucleic acids, viruses, pharmaceuticals and / or pharmaceutical compositions or formulations can increase polypeptide levels (transcript or protein levels) in one or more contacted or treated cells of the subject by at least about twofold, at least about threefold, at least about fourfold, at least about fivefold, at least about sixfold, at least about sevenfold, at least about eightfold, at least about ninefold, at least about tenfold, at least about fifteenfold, at least about twentyfold, at least about 25fold, at least about 50fold, at least about 75fold, at least about 100fold, at least about 250fold, at least about 500fold, at least about 750fold, at least about 1000fold, or more compared to the endogenous levels of polypeptides in one or more corresponding untreated cells of the subject. In some embodiments, one or more contacted or treated cells are one or more cells of the eye. Methods for measuring transcript or protein levels from the sample are well known to those skilled in the art, including, for example, qPCR, Western blotting, and mass spectrometry.

[0130] Other aspects of this disclosure relate to methods for providing preventive, mitigating, or therapeutic relief for one or more signs or symptoms of an ocular condition or disease in a subject in need, comprising administering an effective amount of any recombinant nucleic acid, virus, pharmaceutical and / or pharmaceutical composition or formulation described herein to the subject. In some embodiments, the subject is human. In some embodiments, the subject suffers from an ocular condition or disease. In some embodiments, the ocular condition or disease is retinitis pigmentosa, recessive retinitis pigmentosa, severe recessive retinitis pigmentosa, dominant retinitis pigmentosa, dominant retinitis pigmentosa with choroidal lesions, recessive retinitis pigmentosa with parapeteropallor preservation of RPE (PPRPE), recessive retinitis pigmentosa with posterior column ataxia (PCARP), recessive retinitis pigmentosa with microcytosis, symptomatic recessive retinitis pigmentosa, recessive symptomatic disease with retinitis pigmentosa, non-symptomatic recessive retinitis pigmentosa, non-symptomatic dominant retinitis Retinitis pigmentosa, symptomatic dominant retinitis pigmentosa, juvenile recessive retinitis pigmentosa, recessive retinitis pigmentosa and intellectual disability, recessive retinitis pigmentosa with macular degeneration, severe early-onset recessive retinitis pigmentosa, recessive retinitis pigmentosa and bone malformations, recessive retinitis pigmentosa and skeletal abnormalities, dominant retinitis pigmentosa with sensorineural hearing loss, recessive retinitis pigmentosa with hearing loss, recessive retinitis pigmentosa with hearing loss and additional disability, recessive retinitis pigmentosa with vitreous degeneration, early-onset recessive retinitis pigmentosa with macular defect Retinitis pigmentosa, X-linked retinitis pigmentosa, recessive X-linked retinitis pigmentosa, dominant X-linked retinitis pigmentosa, severe X-linked retinitis pigmentosa, X-linked retinitis pigmentosa with intellectual disability, X-linked retinitis pigmentosa with myopathy, Valday-Beedl-like retinitis pigmentosa, Valday-Beedl-like recessive retinitis pigmentosa, bigenic retinitis pigmentosa, bigenic retinitis pigmentosa with retinal outer segment membrane protein 1, bigenic retinitis pigmentosa with PRPH2, recessive retinitis pigmentosa with early macular lesions, recessive hearing loss without retinitis pigmentosa, recessive congenital hearing loss without retinitis pigmentosa, recessive retinitis pigmentosa and recessive ataxia, recessive retinitis pigmentosa and dominant ataxia, mitochondrial retinitis pigmentosa, mitochondrial retinitis pigmentosa with developmental and neurological abnormalities, mitochondrial retinitis pigmentosa with progressive sensorineural hearing loss, mitochondrial retinitis pigmentosa with hearing loss and neurological abnormalities, autosomal dominant retinitis pigmentosa, non-symptomatic autosomal dominant retinitis pigmentosa,Autosomal recessive retinitis pigmentosa, non-syndromic autosomal recessive retinitis pigmentosa, retinal pigment epithelium (RPE), recessive RPE, dominant RPE, recessive RPE degeneration, dominant RPE degeneration, ataxia, recessive ataxia, dominant ataxia, Senior-Loken syndrome, recessive Senior-Loken syndrome, dominant Senior-Loken syndrome, nephronoplasia, recessive nephronoplasia, dominant nephronoplasia, adolescent recessive nephronoplasia, ciliopathy-associated recessive nephronoplasia, juvenile nephronoplasia, juvenile recessive nephronoplasia, juvenile dominant nephronoplasia, Usher syndrome, Usher syndrome type I, Usher syndrome type II, Usher syndrome Group III, recessive Usher syndrome, atypical recessive Usher syndrome, dominant Usher syndrome, type 2 recessive Usher syndrome, type 2a recessive Usher syndrome, type 3 recessive Usher syndrome, type 3-like recessive Usher syndrome, atypical recessive Usher syndrome, type 1 recessive Usher syndrome, type 1b recessive Usher syndrome, type 1d recessive Usher syndrome, type 1f recessive Usher syndrome, type 1J recessive Usher syndrome, type 1k recessive Usher syndrome, dizygotic Usher syndrome with CDH23, dizygotic Usher syndrome with PCDH15, acadian recessive Usher syndrome, recessive atypical Usher syndrome (USH3-like), Leber's congenital amaurosis, recessive Leber's congenital amaurosis, dominant Leber's congenital amaurosis, de novo Leber's congenital amaurosis, dominant Leber's congenital amaurosis with pituitary dysfunction, recessive Leber's congenital amaurosis with myopathy, recessive Leber's congenital amaurosis with severe childhood retinal dystrophy, mitochondrial Leber hereditary optic neuropathy, Leber's hereditary optic neuropathy, optic nerve atrophy, recessive optic nerve atrophy, dominant optic nerve atrophy, optic nerve atrophy with ataxia, recessive optic nerve atrophy with ataxia, with ataxia Dominant optic atrophy, recessive optic atrophy with ataxia and 3-methylglutaconic aciduria, dominant optic atrophy with cataracts, ataxia and anreflexia, Kahr-type dominant optic atrophy, dominant optic atrophy with sensorineural hearing loss, recessive cerebellar degeneration with optic atrophy, optic atrophy with anesthesia-dystonia syndrome, X-linked optic atrophy with anesthesia-dystonia syndrome, retinal dystrophy, recessive retinal dystrophy, dominant retinal dystrophy, hereditary retinal dystrophy, early-onset recessive retinal dystrophy, recessive symptomatic retinal dystrophy, recessive non-symptomatic retinal dystrophy,Recessive symptomatic and asymptomatic retinal dystrophy, recessive optic atrophy and retinal dystrophy, recessive retinal dystrophy and obesity, recessive retinal dystrophy and cerebellar dysplasia, symptomatic recessive optic atrophy and retinal dystrophy, dominant retinal dystrophy with iris defects, ciliopathy spectrum including retinal dystrophy, recessive ciliopathy spectrum including retinal dystrophy, dominant ciliopathy spectrum including retinal dystrophy, dominant optic atrophy with neuropathy and myopathy, dominant optic atrophy with intellectual disability and developmental delay, symptomatic optic atrophy , non-symptomatic optic nerve atrophy, recessive non-symptomatic optic nerve atrophy, dominant non-symptomatic optic nerve atrophy, recessive symptomatic optic nerve atrophy, dominant symptomatic optic nerve atrophy, Charcot-Marie-Tooth disease, recessive Charcot-Marie-Tooth disease, dominant Charcot-Marie-Tooth disease, benign spotted retina, recessive benign spotted retina, dominant benign spotted retina, symptomatic retinopathy, recessive symptomatic retinopathy, dominant symptomatic retinopathy, Batten disease, recessive Batten disease, dominant Batten disease, recessive Batten disease (neuroceroid lipofuscinosis type 3), juvenile recessive Batten disease (neuroceroid lipofuscinosis type 3), neuroceroid lipofuscinosis, recessive Ceroid lipofuscinosis of the nervous system, recessive ceroid lipofuscinosis type 1, dominant ceroid lipofuscinosis, Stargart disease, recessive Stargart disease, dominant Stargart disease, juvenile Stargart disease, late-onset Stargart disease, Stargart-like macular dystrophy, recessive Stargart-like macular dystrophy, dominant Stargart-like macular dystrophy, macular dystrophy, recessive macular dystrophy, early-onset macular dystrophy, adult-onset macular dystrophy, early-onset recessive macular dystrophy, adult-onset recessive macular dystrophy, early adult-onset recessive macular dystrophy Sexual macular dystrophy, juvenile recessive macular dystrophy with hypotrichosis, dominant macular dystrophy, late-onset dominant macular dystrophy, dominant macular dystrophy with lens zonules, bullseye dominant macular dystrophy, butterfly-shaped dominant macular dystrophy, age-related dominant macular dystrophy, benign concentric annular dominant macular dystrophy, vitelloid recessive macular dystrophy, vitelloid dominant macular dystrophy, atypical vitelloid dominant macular dystrophy, dominant adult-type vitelloid macular dystrophy, Stargard-type dominant macular dystrophy, Stargard-type dominant macular dystrophy,North Carolina dominant macular dystrophy, North Carolina-like dominant macular dystrophy, North Carolina-like dominant macular dystrophy with progressive sensorineural hearing loss, cystoid dominant macular dystrophy, Best-type dominant macular dystrophy, occult macular dystrophy, recessive occult macular dystrophy, dominant occult macular dystrophy, age-related familial macular dystrophy, X-linked atrophic macular dystrophy, recessive X-linked atrophic macular dystrophy, dominant X-linked atrophic macular dystrophy, mitochondrial macular pattern dystrophy with type II diabetes and hearing loss Rophy, yellow spot fundus, recessive yellow spot fundus, dominant yellow spot fundus, rod dystrophy, recessive rod dystrophy, dominant rod dystrophy, cone dystrophy, recessive cone dystrophy, dominant cone dystrophy, recessive cone dystrophy with supernormal rod electroretinogram, early-onset recessive cone dystrophy, late-onset recessive cone dystrophy, cone dystrophy 1, X-linked cone dystrophy 1, cone dystrophy 2, progressive cone dystrophy 2, X-linked progressive cone dystrophy 2, delayed cone adaptation, recessive delayed cone adaptation, dominant delayed cone adaptation, cone rod Rod-condylophysical dystrophy, recessive rod-condylophysical dystrophy, dominant rod-condylophysical dystrophy, solitary rod-condylophysical dystrophy, progressive rod-condylophysical dystrophy, X-linked rod-condylophysical dystrophy, X-linked progressive rod-condylophysical dystrophy, progressive dominant rod-condylophysical dystrophy, rod-condylophysical dystrophy and enamel hypoplasia syndrome, recessive rod-condylophysical dystrophy and enamel hypoplasia syndrome, dominant rod-condylophysical dystrophy and enamel hypoplasia syndrome, recessive rod-condylophysical dystrophy with internal retinopathy, recessive rod-condylophysical dystrophy with bone disease, congenital disorders Symptomatic non-progressive recessive pyramidal-rodylosis, recessive pyramidal-rodylosis with hearing loss, recessive pyramidal-rodylosis with psychomotor retardation, recessive pyramidal and pyramidal-rodylosis, pyramidal-rodylosis synaptic disease, congenital pyramidal-rodylosis synaptic disease, recessive congenital pyramidal-rodylosis synaptic disease, dominant congenital pyramidal-rodylosis synaptic disease, rod-pyramidal dystrophy, recessive rod-pyramidal dystrophy, dominant rod-pyramidal dystrophy, early-onset recessive rod-pyramidal dystrophy, non-symptomatic recessive rod-pyramidal dyst...

Claims

1. A recombinant herpesvirus genome comprising one or more polynucleotides encoding a polypeptide.

2. A recombinant herpesvirus genome according to claim 1, having replication ability.

3. The recombinant herpesvirus genome according to claim 1, which is a replication defect.

4. A recombinant herpesvirus genome according to any one of claims 1 to 3, selected from the group consisting of recombinant herpes simplex virus genome, recombinant varicella-zoster virus genome, recombinant human cytomegalovirus genome, recombinant herpesvirus 6A genome, recombinant herpesvirus 6B genome, recombinant herpesvirus 7 genome, recombinant Epstein-Barr virus genome, recombinant Kaposi's sarcoma-associated herpesvirus genome, and any derivative thereof.

5. A recombinant herpes simplex virus genome according to any one of claims 1 to 4.

6. The recombinant herpesvirus genome according to claim 5, wherein the recombinant herpesvirus genome is a recombinant herpesvirus type 1 (HSV-1) genome, a recombinant herpesvirus type 2 (HSV-2) genome, or any derivative thereof.

7. The recombinant herpesvirus genome according to claim 5 or claim 6, wherein the recombinant herpesvirus genome is a recombinant herpesvirus type 1 (HSV-1) genome.

8. The recombinant herpesvirus genome according to any one of claims 4 to 7, wherein the recombinant herpesvirus genome is manipulated to reduce or eliminate the expression of one or more toxic herpesvirus genes.

9. The recombinant herpes simplex virus genome according to any one of claims 4 to 8, wherein the recombinant herpes simplex virus genome includes an inactivating mutation.

10. The recombinant herpesvirus genome according to claim 9, wherein the inactivating mutation is present in the herpes simplex virus gene.

11. The recombinant herpesvirus genome according to claim 10, wherein the inactivating mutation is a deletion of the coding sequence of the herpes simplex virus gene.

12. The recombinant herpesvirus genome according to claim 10 or claim 11, wherein the herpes simplex virus gene is selected from the group consisting of infecting cell protein (ICP) 0, ICP4, ICP22, ICP27, ICP47, thymidine kinase (tk), long unique region (UL) 41, and UL55.

13. The recombinant herpes simplex virus genome according to claim 12, wherein the recombinant herpes simplex virus genome comprises an inactivating mutation in one or both copies of the ICP4 gene.

14. The recombinant herpes simplex virus genome according to claim 12 or claim 13, wherein the recombinant herpes simplex virus genome includes an inactivating mutation in the ICP22 gene.

15. The recombinant herpes simplex virus genome according to any one of claims 12 to 14, wherein the recombinant herpes simplex virus genome includes an inactivating mutation in the UL41 gene.

16. The recombinant herpes simplex virus genome according to any one of claims 12 to 15, wherein the recombinant herpes simplex virus genome comprises an inactivating mutation in one or both copies of the ICP0 gene.

17. The recombinant herpes simplex virus genome according to any one of claims 12 to 16, wherein the recombinant herpes simplex virus genome includes an inactivating mutation in the ICP27 gene.

18. The recombinant herpes simplex virus genome according to any one of claims 12 to 17, wherein the recombinant herpes simplex virus genome includes an inactivating mutation in the UL55 gene.

19. The recombinant herpes simplex virus genome according to any one of claims 12 to 18, wherein the recombinant herpes simplex virus genome does not contain an inactivating mutation in the ICP47 gene.

20. The recombinant herpesvirus genome according to any one of claims 12 to 19, wherein the recombinant herpes simplex virus does not contain an inactivating mutation in either one copy or both copies of the ICP34.5 gene.

21. The recombinant herpes simplex virus genome according to any one of claims 4 to 20, wherein the recombinant herpes simplex virus genome comprises one or more polynucleotides encoding the polypeptide within one or both loci of the ICP4 viral gene locus.

22. The recombinant herpes simplex virus genome according to any one of claims 4 to 21, wherein the recombinant herpes simplex virus genome comprises one or more polynucleotides encoding the polypeptide within the ICP22 viral locus.

23. The recombinant herpes simplex virus genome according to any one of claims 4 to 22, wherein the recombinant herpes simplex virus genome comprises one or more polynucleotides encoding the polypeptide within the UL41 viral locus.

24. The recombinant herpes simplex virus genome according to any one of claims 4 to 23, wherein the recombinant herpes simplex virus genome comprises one or more polynucleotides encoding the polypeptide within one or both loci of the ICP0 viral gene locus.

25. The recombinant herpes simplex virus genome according to any one of claims 4 to 24, wherein the recombinant herpes simplex virus genome comprises one or more polynucleotides encoding the polypeptide within the ICP27 viral locus.

26. The recombinant herpes simplex virus genome according to any one of claims 4 to 25, wherein the recombinant herpes simplex virus genome comprises one or more polynucleotides encoding the polypeptide within the UL55 viral locus.

27. The recombinant herpesvirus genome according to any one of claims 1 to 26, wherein the polypeptide is a human polypeptide.

28. The polypeptide comprises steryl α-motif domain-containing protein 11, nephrocystin-4, espin, nicotinamide / nicotinic acid mononucleotide adenylyltransferase 1, mitofusin-2, ER membrane protein complex subunit 1, phospholipase A2 group V, dehydrodritilyl diphosphate synthase complex subunit, palmitoyl protein thioesterase 1, very long-chain fatty acid elongation protein 1, protein O-linked mannose β-1,2-N-acetylglucosaminyltransferase 1, and retinoic acid Doisomerohydrolase, retina-specific phospholipid transport ATPase, collagen α-1 (XI), guanine nucleotide-binding protein G(t) subunit α-2, chloride channel CLIC-like protein 1, DNA damage-modulating autophagy modulator protein 2, U4 / U6 nuclear small ribonucleoprotein Prp3, α-endosulfin, semaphorin-4A, cyclic AMP-dependent transcription factor ATF-6α, hemisentin-1, complement factor H, Crams protein homolog 1, adiponectin receptor protein 1, protein RD3, serine / threonine protein kinase Nek2, feline leukemia virus subgroup C receptor-related protein 1, usherin, serologically defined colon cancer antigen 8, olfactory receptor 2W3, NBAS subunit of NRZ tethering factor complex, cytoplasmic carboxypeptidase-like protein 5, zinc finger protein 513, flagellar transport protein 172 homolog, photoreceptor ciliary actin regulator, EGF-containing fibrin-like extracellular matrix protein 1 / TLE family member 5, protein FAM1 61A, WD repeat-containing planar cell polarity effector protein Fritz homolog, centrosome-related protein ALMS1, U5 nuclear small ribonucleoprotein 200kDa helicase, metal transporter CNNM4, cyclic nucleotide gate cation channel α-3, nephrocystin-1, tyrosine-protein kinase Mer, Valday-Beedl syndrome 5 protein, ceramide kinase-like protein, neurogenic differentiation factor 1, transmembrane protein 237, inward rectifying potassium channel 13, S-arrestin, secreted phosphoprotein 24, CCA tRNA nucleotidyltransferase 1 (mitochondria),Sodium bicarbonate cotransporter 3, leucine zipper transcription factor-like protein 1, guanine nucleotide-binding protein G(t) subunit α-1, 3-prime repair exonuclease 1, MAP kinase-activated protein kinase 3, ataxin-7, vitamin K-dependent protein S, ADP ribosylation factor-like protein 6, photoreceptor matrix proteoglycan 2, IQ calmodulin-binding motif-containing protein 1, rhodopsin, nephrocystin-3, clarine-1, putative cationic amino acid transporter / solute carrier family 7 members 14, choline phosphate cytidylyltransferase A, 19kDa centrosome protein, rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit β, wolframin, homeobox protein HM X1, Ras-related protein Rab-28, Coiled-coil C2 domain-containing protein 2A, Prominin-1, Adhesion-type G protein-coupled receptor A3, Death domain-containing protein 1, WD repeat-containing protein 19, cGMP gated cation channel α-1, CDGSH iron-sulfur domain-containing protein 2, Microsomal triglyceride transport protein large subunit, Leucine-rich repeat, Immunoglobulin-like domain / transmembrane domain-containing protein 3, Valday-Beedl syndrome protein 7, Valday-Beedl syndrome protein 12, Major promoter superfamily domain-containing protein 8, Serine / threonine-protein kinase PLK4, Lecithin retinol acyltransferase, Toll-like receptor 3, Cytochrome P450 4V2, Spliceosome-related protein CWC27 homolog, Centrosome protein POC5, Versican core protein, Adhesion-type G protein-coupled receptor V1, COUP transcription factor 1, Mitochondrial outer membrane protein SLC25A46, Catenin α-1, Histidine--tRNA ligase (cytoplasm), Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit α, Metabotropic glutamate receptor 6, Serine / threonine-protein kinase MAK, Complement C2, Complement factor B, Tubby-related protein 1, Guanylyl cyclase-activated protein 1, Guanylyl cyclase-activated protein 2, Peripherin-2, Photoreceptor matrix proteoglycan 1, I-Shut homolog protein,Collagen α-1(IX) chain, regulatory synaptic membrane exocytosis protein 1, level cylin, extra-long chain fatty acid elongation protein 4, PR domain zinc finger protein 13, reticulon-4 interacting protein 1 (mitochondria), jubelin, peroxisome targeting signal 2 receptor, CCR4-NOT transcription complex subunit 9, aromatic hydrocarbon receptor, Kelch-like protein 7, retinitis pigmentosa protein 9, protein PTHB 1, peroxisome ATPase PEX 1, tetraspanin-1 2, inosine-5'-monophosphate dehydrogenase 1, shortwave sensitive opsin 1, UPF0606 protein KIAA1549, retinitis pigmentosa-like protein 1, disintegrin / metalloproteinase domain-containing protein 9, heparan-α-glucosaminid N-acetyltransferase, oxygen regulatory protein 1, α-tocopherol transport protein, centrosome / spindle pole-related protein 1, dynamin-like 120kDa protein (mitochondrial), peroxisome formation factor 2, cyclic nucleotide gate cation channel β-3, ciliary / flagellar-related protein 418, growth / differentiation factor 6, regulatory synaptic membrane exocytosis protein 2, voltage-gated potassium channel superfamily V member 2, E3 ubiquitin protein ligase Topors, 78kDa centrosome protein, inversin, U4 / U6 nuclear small ribonucleoprotein Prp4, Warlin, E3 ubiquitin protein ligase TRIM32, Toll-like receptor 4, cytoplasmic dynein 2 intermediate chain 2, programmed cell death protein 2, exosome complex component RRP4, phosphatidylinositol polyphosphate 5-phosphatase type IV, phytanoyl-CoA dioxygenase (peroxisome), acyl-CoA binding domain-containing protein, protocadherin-15, retinol-binding protein 3, DNA excision repair protein ERCC-6, hexokinase-1, cadherin-23, cadherin-related family member 1, RPE retinal G protein-coupled receptor, kinesin-like protein KIF11, retinol-binding protein 4, cone cGMP-specific 3',5'-cyclic phosphodiesterase subunit α, paired-box protein Pax-2, PDZ domain-containing protein 7,ADP ribosylation factor-like protein 3, BBSome interaction protein 1, age-related macular degeneration-sensitive protein 2, serine protease HTRA 1, ornithine aminotransferase (mitochondrial), zinc finger protein 408, Tubby protein homolog, transcription enhancer factor TEF-1, harmonin, transmembrane protein 216, bethroffin-1, isoaspartyl peptidase / L-asparaginase, rod extrasegmental membrane protein 1, Valday-Beedl syndrome 1 protein, Calcium-binding protein 4, low-density lipoprotein receptor-related protein 5, calpain-5, atypical myosin-VIIa, transmembrane protein 126A, frizzled-4, cytoplasmic dynein 2 light intermediate chain 1, 164kDa centrosome protein, complement C1q tumor necrosis factor-related protein 5, membrane frizzled-related protein, voltage-gated calcium channel subunit α-2 / δ-4, guanine nucleotide-binding protein G(I) / G(S) / G(T) subunit β-3, retinal cone rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit γ, collagen α-1(II) chain, matrix metalloproteinase-19, retinol dehydrogenase 5, T complex protein 1 subunit β, Balday-Beedl syndrome 10 protein, 290kDa centrosome protein, POC1 centriole protein homolog B, mevalonate kinase, flagellar transport protein 81 homolog, mitochondrial translation termination factor in rescue, intrinsic membrane protein 2B, retinoblastoma-associated protein, RCC1 and BTB domain-containing protein 1, rhodopsin kinase GRK1, X-linked retinitis pigmentosa GTPase Regulatory factor interaction protein 1, neuroretinal specific leucine zipper protein, homeobox protein OTX2, retinol dehydrogenase 11, retinol dehydrogenase 12, tubulin polyglutamylase TTLL5, spermatogenesis-related protein 7, tetratricopeptide repeat protein 8, fibrin-5, transient receptor potential cation channel subfamily M member 1, γ-tubulin complex component 4, sodium / potassium / calcium exchanger 1, photoreceptor-specific nuclear receptor, Valday-Beedl syndrome 4 protein, calcium and integrin-binding family member 2,Retinaldehyde-binding protein 1, N-acetylglucosamine-1-phosphotransferase subunit γ, flagellar transport protein 140 homolog, clatherin-related protein 1, ATP-binding cassette subfamily C member 6, ketimin reductase μ-crystallin, battenin, zinc finger protein 423, protein phantom, Valday-Beedl syndrome 2 protein, ADP-ribosylation factor-like protein 2 binding protein, cyclic nucleotide gate cation channel β-1, cadherin-3, premRNA splicing factor, ATP-dependent RNA helicase PRP16, thrombospondin motif A disintegrin metalloproteinase with 18, solute carrier family 38 member 8, retinal guanylyl cyclase 1, premRNA processing splicing factor 8, aromatic hydrocarbon interacting protein-like 1, membrane-bound phosphatidylinositol transport protein 3, protein unc-119 homolog A, putative G protein-coupled receptor 179, tectonic-like complex member MKS1, carbonic anhydrase 4, G protein signaling regulator 9, aryl sulfatase G, premRNA splicing regulator USH1G, photoreceptor disk component PRCD, phascin-2, retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit γ, laminin subunit α-1, AFG3-like protein 2, cone-rod homeobox protein, receptor expression-enhancing protein 6, anterior retinal nerve fold homeobox protein 2, complement C3, Rho guanine nucleotide exchange factor 18, patatin-like phospholipase domain-containing protein 6, G protein signaling regulator 9-binding protein, optic nerve atrophy protein 3, U4 / U6 nuclear small ribonucleoprotein Prp31, isocitrate dehydrogenase [NAD] subunit β (mitochondria), pantothenate kinase 2 (mitochondria), protein jagged-1, molecular chaperone MKKS, centrosome protein kizuna, lysophosphatidylserine lipase ABHD12, kinesin-like protein KIF3B, centrosome-related protein CEP250, premRNA processing factor 6, ciliary-flagellar-related protein 410, dynamin-1-like protein,Metalloproteinase inhibitor 3, flagellar transport protein 27 homolog, fibrin-1, MIEF1 upstream open reading frame protein, aconitate hydratase (mitochondria), γ-tubulin complex component 6, centrioles / centronome satellite proteins, retinosuxin, protein XRP2, dystrophin, X-linked retinitis pigmentosa GTPase regulator, nictaropine, Xaa-prodipeptidase, noline, voltage-gated L-type calcium channel subunit α-1F, phosphoglycerate kinase 1, Rab protein geranylgeranyltransferase component A1, mitochondrial import inner membrane transport enzyme subunit Tim8 A, ribose phosphate pyrophosphokinase 1, long-wave sensitive opsin 1, medium-wave sensitive opsin 1, short-wave sensitive opsin 1, transcription factor A (mitochondria), NADH ubiquinone oxidoreductase chain 1, NADH ubiquinone oxidoreductase chain 2, NADH ubiquinone oxidoreductase chain 3, NADH ubiquinone oxidoreductase chain 4L, NADH ubiquinone oxidoreductase chain 4, NADH ubiquinone oxidoreductase chain 5, NADH ubiquinone oxidoreductase chain 6, ATP synthase subunit a, ATP synthase protein 8, cytochrome c oxidase subunit 1, cytochrome c oxidase subunit 3, cytochrome b, ro, Icin-tRNA ligase (mitochondrial), indiscriminate glutamyl-tRNA synthetase EARS2 (mitochondrial), lysine-tRNA ligase, histidine-tRNA ligase (mitochondrial), serine-tRNA ligase (mitochondrial), putative proline-tRNA ligase (mitochondrial), cyanocobalamin reductase / alkylcobalamin dealkylase, POU domain, class 3, transcription factor 4, ribosomal protein S6 kinase α-6, ciliation and planar polarity effector 1, Meckelin, TRAF3 interaction protein 1, Flagellar transport protein 74 homolog, S-phase cyclin A-related protein in the endoplasmic reticulum, sodium channel and clathrin linker 1, protein TALPID3, tectonic-2, ADP-ribosylation factor-like protein 13B, B9 domain-containing protein 1, B9 domain-containing protein 2, C2 domain-containing protein 3, 41kDa centrosome protein, 104kDa centrosome protein, 120kDa centrosome protein, flagellar transport protein 172 homolog, katanin-interacting protein, kinesin-like protein KIF7, retinal rod rhodopsin-sensitive cGMP A recombinant herpesvirus genome according to any one of claims 1 to 27, selected from the group consisting of 3',5'-cyclic phosphodiesterase subunit δ, tectonic-1, tectonic-3, transmembrane protein 107, transmembrane protein 138, transmembrane protein 231, tetratricopeptide repeat protein 21B, nuclear receptor ROR-α, β nerve growth factor, collagen α-2 (VIII) chain, solute carrier family 4 member 11, zinc finger E-box linked homeobox 1, keratin type II cuticle Hb3, keratin type I cytoskeleton 12, transforming growth factor-β-inducing protein ig-h3, tumor-associated calcium signaling factor 2, carbohydrate sulfotransferase 6, gelzolin, UbiA prenyltransferase domain-containing protein 1, decorin, 1-phosphatidylinositol 3-phosphate 5-kinase, transcription factor Ovo-like 2, and Grainyhead-like protein 2 homolog.

29. The recombinant herpesvirus genome according to claim 28, wherein the polypeptide comprises a sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with an amino acid sequence selected from the group consisting of SEQ ID NO: 21-377, SEQ ID NO: 739, and SEQ ID NO:

740.

30. The recombinant herpesvirus genome according to any one of claims 1 to 29, wherein the polypeptide is β-nerve growth factor, retina-specific phospholipid transport ATPase, or 290 kDa centrosome protein.

31. The recombinant herpesvirus genome according to any one of claims 1 to 30, wherein the polypeptide is β-nerve growth factor.

32. The recombinant herpesvirus genome according to claim 31, wherein the β-nerve growth factor comprises a sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with respect to the amino acid sequence of SEQ ID NO: 363, SEQ ID NO: 739, or SEQ ID NO:

740.

33. The recombinant herpesvirus genome according to claim 31 or 32, wherein the β-nerve growth factor comprises a sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with respect to the amino acid sequence of SEQ ID NO:

740.

34. The recombinant herpesvirus genome according to any one of claims 1 to 30, wherein the polypeptide is a retina-specific phospholipid transport ATPase.

35. The recombinant herpesvirus genome according to claim 34, wherein the retina-specific phospholipid transport ATPase comprises a sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with respect to the amino acid sequence of SEQ ID NO:

33.

36. The recombinant herpesvirus genome according to any one of claims 1 to 30, wherein the polypeptide is a 290 kDa centrosome protein.

37. The recombinant herpesvirus genome according to claim 36, wherein the 290kDa centrosome protein comprises a sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with respect to the amino acid sequence of SEQ ID NO:

219.

38. A recombinant herpesvirus genome according to any one of claims 1 to 37, which, when introduced into target cells, exhibits reduced cytotoxicity compared to the corresponding wild-type herpesvirus genome.

39. The recombinant herpesvirus genome according to claim 38, wherein the target cell is a human cell.

40. The recombinant herpesvirus genome according to claim 38 or claim 39, wherein the target cell is an eye cell.

41. The recombinant herpesvirus genome according to any one of claims 38 to 40, wherein the target cells are corneal epithelial cells, rod cells, cone cells, photoreceptors, retinal pigment epithelial cells, retinal ganglion cells, bipolar cells, horizontal cells, Müller cells, or axonless cells.

42. A herpesvirus comprising the recombinant herpesvirus genome described in any one of claims 1 to 41.

43. The herpes virus according to claim 42, having replication ability.

44. The herpesvirus according to claim 42, which is replication-deficient.

45. A herpesvirus according to any one of claims 42 to 44, having reduced cytotoxicity compared to the corresponding wild-type herpesvirus.

46. A herpesvirus according to any one of claims 42 to 45, selected from the group consisting of herpes simplex virus, varicella-zoster virus, human cytomegalovirus, herpesvirus 6A, herpesvirus 6B, herpesvirus 7, Epstein-Barr virus, and Kaposi's sarcoma-associated herpesvirus.

47. A herpes simplex virus, as described in any one of claims 42 to 46.

48. The herpesvirus according to claim 46 or claim 47, wherein the herpes simplex virus is herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2), or any derivative thereof.

49. The herpesvirus according to any one of claims 46 to 48, wherein the herpes simplex virus is herpes simplex virus type 1 (HSV-1).

50. A pharmaceutical composition comprising a recombinant herpesvirus genome according to any one of claims 1 to 41 or a herpesvirus according to any one of claims 42 to 49, and a pharmaceutically acceptable excipient.

51. The pharmaceutical composition according to claim 50, suitable for administration in the eye, subretinal, intraocular, intravitreous, anterior chamber, topical, subcutaneous, subconjunctival, sub-Tenon's, sub-Tenon's capsule, anterior chamber, retroocular, systemic, parenteral, periocular, juxtascleral, anterior juxtascleral, posterior juxtascleral, oral, periocular, or choroidal.

52. A pharmaceutical composition according to claim 50 or claim 51, suitable for intraocular, subretinal, intravitreous, anterior chamber, suprachoroidal, or topical administration.

53. A pharmaceutical composition according to any one of claims 50 to 52, suitable for choroidal or topical administration.

54. A pharmaceutical composition according to any one of claims 50 to 53, suitable for administration via the choroid.

55. A pharmaceutical composition according to any one of claims 50 to 53, suitable for topical administration.

56. A pharmaceutical composition according to any one of claims 50 to 55, suitable for use in eye drops, ointments, pastes, creams, suspensions, emulsions, fatty ointments, gels, bioadhesive gels, powders, lotions, solutions, sprays, or any combination thereof.

57. The pharmaceutical composition according to any one of claims 50 to 56, wherein the herpes virus or pharmaceutical composition is formulated as eye drops, ointment, paste, cream, suspension, emulsion, fatty ointment, gel, bioadhesive gel, powder, lotion, solution, or spray.

58. A herpes virus according to any one of claims 42 to 49 or a pharmaceutical composition according to any one of claims 50 to 57, for use as a pharmaceutical.

59. Optionally, the herpesvirus or pharmaceutical composition is intended for use in the treatment of an eye condition or disease, and optionally, the eye condition or disease is retinitis pigmentosa, recessive retinitis pigmentosa, severe recessive retinitis pigmentosa, dominant retinitis pigmentosa, dominant retinitis pigmentosa with choroidal lesions, recessive retinitis pigmentosa with parapeteropallor preservation of RPE (PPRPE), recessive retinitis pigmentosa with posterior column ataxia (PCARP), recessive retinitis pigmentosa with microcytosis, symptomatic recessive retinitis pigmentosa, recessive symptomatic disease with retinitis pigmentosa, non-symptomatic recessive retinitis pigmentosa, non-symptomatic dominant retinitis pigmentosa, Symptomatic dominant retinitis pigmentosa, juvenile recessive retinitis pigmentosa, recessive retinitis pigmentosa and intellectual disability, recessive retinitis pigmentosa with macular degeneration, severe early-onset recessive retinitis pigmentosa, recessive retinitis pigmentosa and bone malformations, recessive retinitis pigmentosa and skeletal abnormalities, dominant retinitis pigmentosa with sensorineural hearing loss, recessive retinitis pigmentosa with hearing loss, recessive retinitis pigmentosa with hearing loss and additional disability, recessive retinitis pigmentosa with vitreous degeneration, early-onset recessive retinitis pigmentosa with macular defect, X-linked retinitis pigmentosa, recessive X-linked retinitis pigmentosa, dominant X-linked retinitis pigmentosa, severe X-linked retinitis pigmentosa, intellectual disability X-linked retinitis pigmentosa with myopathy, X-linked retinitis pigmentosa with myopathy, Valday-Beedl-like retinitis pigmentosa, Valday-Beedl-like recessive retinitis pigmentosa, bigenic retinitis pigmentosa, bigenic retinitis pigmentosa with retinal outer segment membrane protein 1, bigenic retinitis pigmentosa with PRPH2, recessive retinitis pigmentosa with early macular lesions, recessive hearing loss without retinitis pigmentosa, recessive congenital hearing loss without retinitis pigmentosa, recessive retinitis pigmentosa and recessive ataxia, recessive retinitis pigmentosa and dominant ataxia, mitochondrial retinitis pigmentosa, mitochondrial retinitis with developmental and neurological abnormalities Mitochondrial retinitis pigmentosa, progressive sensorineural hearing loss, mitochondrial retinitis pigmentosa with hearing loss and neurological abnormalities, autosomal dominant retinitis pigmentosa, asymptomatic autosomal dominant retinitis pigmentosa, autosomal recessive retinitis pigmentosa, asymptomatic autosomal recessive retinitis pigmentosa, retinal pigment epithelium (RPE), recessive RPE, dominant RPE, recessive RPE degeneration, dominant RPE degeneration, ataxia, recessive ataxia, dominant ataxia, Senior-Loken syndrome, recessive Senior-Loken syndrome, dominant Senior-Loken syndrome, nephronoplasia, recessive nephronoplasia, dominant nephronoplasia, adolescent recessive nephronoplasia,Ciliopathy-associated recessive nephronoplasia, juvenile nephronoplasia, juvenile recessive nephronoplasia, juvenile dominant nephronoplasia, Usher syndrome, Usher syndrome type I, Usher syndrome type II, Usher syndrome type III, recessive Usher syndrome, atypical recessive Usher syndrome, dominant Usher syndrome, type 2 recessive Usher syndrome, type 2a recessive Usher syndrome, type 3 recessive Usher syndrome, type 3-like recessive Usher syndrome, atypical recessive Usher syndrome, type 1 recessive Usher syndrome, type 1b recessive Usher syndrome, type 1d recessive Usher syndrome, type 1f recessive Usher syndrome Syndrome, 1J recessive Usher syndrome, 1k recessive Usher syndrome, bigenic Usher syndrome with CDH23, bigenic Usher syndrome with PCDH15, Acadian recessive Usher syndrome, recessive atypical Usher syndrome (USH3-like), Leber's congenital amaurosis, recessive Leber's congenital amaurosis, dominant Leber's congenital amaurosis, de novo Leber's congenital amaurosis, dominant Leber's congenital amaurosis with pituitary dysfunction, recessive Leber's congenital amaurosis with myopathy, recessive Leber's congenital amaurosis with severe childhood retinal dystrophy Monocular optic neuropathy, mitochondrial Leber hereditary optic neuropathy, Leber hereditary optic neuropathy, optic atrophy, recessive optic atrophy, dominant optic atrophy, optic atrophy with ataxia, recessive optic atrophy with ataxia, dominant optic atrophy with ataxia, recessive optic atrophy with ataxia and 3-methylglutaconic aciduria, cataract, dominant optic atrophy with ataxia and anreflexia, Kjer type dominant optic atrophy, dominant optic atrophy with sensorineural hearing loss, recessive cerebellar degeneration with optic atrophy, optic atrophy with anesthesia-dystonia syndrome, X-linked anesthesia-dystonia syndrome Ciliary retinal dystrophy, recessive retinal dystrophy, dominant retinal dystrophy, hereditary retinal dystrophy, early-onset recessive retinal dystrophy, recessive symptomatic retinal dystrophy, recessive asymptomatic retinal dystrophy, recessive symptomatic and asymptomatic retinal dystrophy, recessive optic atrophy and retinal dystrophy, recessive retinal dystrophy and obesity, recessive retinal dystrophy and cerebellar dysplasia, symptomatic recessive optic atrophy and retinal dystrophy, dominant retinal dystrophy with iris defects, ciliopathy spectrum including retinal dystrophy,Recessive ciliopathy spectrum including retinal dystrophy, dominant ciliopathy spectrum including retinal dystrophy, dominant optic atrophy with neuropathy and myopathy, dominant optic atrophy with intellectual disability and developmental delay, symptomatic optic atrophy, asymptomatic optic atrophy, recessive asymptomatic optic atrophy, dominant asymptomatic optic atrophy, recessive symptomatic optic atrophy, dominant symptomatic optic atrophy, Charcot-Marie-Tooth disease, recessive Charcot-Marie-Tooth Charcot-Marie-Tooth disease, dominant Charcot-Marie-Tooth disease, benign spotted retina, recessive benign spotted retina, dominant benign spotted retina, symptomatic retinopathy, recessive symptomatic retinopathy, dominant symptomatic retinopathy, Batten disease, recessive Batten disease, dominant Batten disease, recessive Batten disease (neuroceroid lipofuscinosis type 3), juvenile recessive Batten disease (neuroceroid lipofuscinosis type 3), neuroceroid lipofuscinosis, recessive neuroceroid lipofuscinosis, recessive neuroceroid Dolipofuscinosis type 1, dominant neuronal ceroid lipofuscinosis, Stargart disease, recessive Stargart disease, dominant Stargart disease, juvenile Stargart disease, late-onset Stargart disease, Stargart-like macular dystrophy, recessive Stargart-like macular dystrophy, dominant Stargart-like macular dystrophy, macular dystrophy, recessive macular dystrophy, early-onset macular dystrophy, adult-onset macular dystrophy Early-onset recessive macular dystrophy, adult-onset recessive macular dystrophy, early adult-onset recessive macular dystrophy, juvenile recessive macular dystrophy with hypotrichosis, dominant macular dystrophy, late-onset dominant macular dystrophy, dominant macular dystrophy with lens zonules, bullseye dominant macular dystrophy, butterfly-shaped dominant macular dystrophy, age-related dominant macular dystrophy, benign concentric annular dominant macular dystrophy. Concentric annular dominant macular dystrophy), vitelloid recessive macular dystrophy, vitelloid dominant macular dystrophy, atypical vitelloid dominant macular dystrophy, dominant adult vitelloid macular dystrophy, Stargard-like dominant macular dystrophy, Stargard-type dominant macular dystrophy, North Carolina dominant macular dystrophy, North Carolina-like dominant macular dystrophy, North Carolina-like dominant macular dystrophy with progressive sensorineural hearing loss, cystic-like dominant macular dystrophy,Best-type dominant macular dystrophy, occult macular dystrophy, recessive occult macular dystrophy, dominant occult macular dystrophy, age-related familial macular dystrophy, X-linked atrophic macular dystrophy, recessive X-linked atrophic macular dystrophy, dominant X-linked atrophic macular dystrophy, mitochondrial macular pattern dystrophy with type II diabetes and hearing loss, yellow spot fundus, recessive yellow spot fundus, dominant yellow spot fundus, rod dystrophy, recessive rod dystrophy, dominant rod dystrophy, cone dystrophy, recessive cone dystrophy, dominant cone Dystrophy, recessive cone dystrophy with supernormal rod electroretinogram, early-onset recessive cone dystrophy, late-onset recessive cone dystrophy, cone dystrophy 1, X-linked cone dystrophy 1, cone dystrophy 2, progressive cone dystrophy 2, X-linked progressive cone dystrophy 2, delayed cone adaptation, recessive delayed cone adaptation, dominant delayed cone adaptation, cone-rod dystrophy, recessive cone-rod dystrophy, dominant cone-rod dystrophy, isolated cone-rod dystrophy, progressive cone-rod dystrophy, X-linked cone-rod dystrophy, X-linked Progressive cone-rod dystrophy, progressive dominant cone-rod dystrophy, cone-rod dystrophy and enamel hypoplasia syndrome, recessive cone-rod dystrophy and enamel hypoplasia syndrome, dominant cone-rod dystrophy and enamel hypoplasia syndrome, recessive cone-rod dystrophy with internal retinopathy, recessive cone-rod dystrophy with bone disease, congenital symptomatic non-progressive recessive cone-rod dystrophy, recessive cone-rod dystrophy with hearing loss, recessive cone-rod dystrophy with psychomotor retardation, recessive cone and cone-rod dystrophy, cone-rod Synaptic disease, congenital pyramidal-rodylosis, recessive congenital pyramidal-rodylosis, dominant congenital pyramidal-rodylosis, rod-pyramidal dystrophy, recessive rod-pyramidal dystrophy, dominant rod-pyramidal dystrophy, early-onset recessive rod-pyramidal dystrophy, non-syndromic recessive rod-pyramidal dystrophy, recessive Newfoundland rod-pyramidal dystrophy, recessive progressive pyramidal dystrophy, Stickler syndrome, dominant Stickler syndrome, recessive Stickler syndrome, dominant Stickler syndrome type I, dominant Stickler syndrome type II, Marshall syndrome, dominant Marshall syndrome,Recessive Marshall syndrome, achromatopsia, recessive monochromacy, dominant monochromacy, recessive complete monochromacy, recessive incomplete monochromacy, macular degeneration, age-related macular degeneration, complex etiology age-related macular degeneration, isolated age-related macular degeneration, wet age-related macular degeneration, dry age-related macular degeneration, drusen, recessive drusen, dominant drusen, early-onset recessive drusen, early-onset dominant drusen, macular drusen, dominant radial macular drusen, parapigmented venous drusen Choroidal retinoretinal atrophy, recessive paravenous retinoretinal atrophy, dominant paravenous retinoretinal atrophy, progressive bifocal chorioretinoretinal atrophy, Valday-Beedl syndrome, recessive Valday-Beedl syndrome, dominant Valday-Beedl syndrome, recessive Valday-Beedl syndrome with developmental abnormalities, retinal degeneration, recessive retinal degeneration, dominant retinal degeneration, non-symptomatic recessive retinal degeneration, Doynn's honeycomb retinal degeneration, Doynn's recessive honeycomb retinal degeneration, Doynn's dominant honeycomb retinal degeneration (Malattia reventinese) Leventinese), recessive nephronoplasia with retinal degeneration, Alström syndrome, recessive Alström syndrome, dominant Alström syndrome, Joubert syndrome, recessive Joubert syndrome, dominant Joubert syndrome, Joubert syndrome, recessive Joubert syndrome, dominant Joubert syndrome, X-linked Joubert syndrome, vitreoretinal degeneration, recessive vitreoretinal degeneration, dominant vitreoretinal degeneration, snowflake vitreoretinal degeneration, snowflake dominant vitreoretinal degeneration, Oguchi disease, recessive Oguchi disease, dominant Oguchi disease, night blindness, congenital night blindness, congenital congenital night blindness, severe congenital night blindness, recessive congenital night blindness, recessive complete congenital night blindness, dominant congenital night blindness, Nogarette type dominant congenital Congenital nyctalopsia, microguchi recessive congenital nyctalopsia, Riggs recessive congenital nyctalopsia, Schubert-Bornschein recessive congenital nyctalopsia, white punctate fundus recessive congenital nyctalopsia, complete recessive congenital nyctalopsia, X-linked congenital nyctalopsia, incomplete X-linked congenital nyctalopsia, retinal vascular disease, cerebral leukodystrophy, retinal vascular disease with cerebral leukodystrophy, recessive retinal vascular disease with cerebral leukodystrophy, dominant retinal vascular disease with cerebral leukodystrophy, Eycardi-Gutierre syndrome, Eycardi-Gutierre syndrome 1, recessive Eycardi-Gutierre syndrome 1, dominant Eycardi-Utierre syndrome 1, lupus frostbite, recessive lupus frostbite,Lupus frostbite dominant, Martinique retinal dystrophy and retinitis pigmentosa, recessive Martinique retinal dystrophy and retinitis pigmentosa, dominant Martinique retinal dystrophy and retinitis pigmentosa, spinocerebellar ataxia, recessive spinocerebellar ataxia, dominant spinocerebellar ataxia, spinocerebellar ataxia with macular dystrophy, spinocerebellar ataxia with retinal degeneration, spinocerebellar ataxia with macular dystrophy or retinal degeneration, recessive spinocerebellar ataxia with macular dystrophy or retinal degeneration, dominant spinocerebellar ataxia with macular dystrophy or retinal degeneration, Wolfram syndrome, recessive Wolfram syndrome, Dominant Wolfram syndrome, low-frequency sensorineural hearing loss, recessive low-frequency sensorineural hearing loss, dominant low-frequency sensorineural hearing loss, ophthalmo-otitis syndrome, recessive ophthalmo-otitis syndrome, dominant ophthalmo-otitis syndrome, recessive kidney, skeletal and retinal abnormalities, recessive abetalipoproteinemia, microcephaly, recessive microcephaly, dominant microcephaly, growth disorders and retinopathy recessive microcephaly, Vietti crystalline corneal-retinal dystrophy, recessive Vietti crystalline corneal-retinal dystrophy, dominant Vietti crystalline corneal-retinal dystrophy, Wagner disease, erosive vitreoretinopathy, Wagner disease and erosive vitreoretinopathy, recessive Wagner disease and erosive vitreoretinopathy, dominant Wagner disease and erosive vitreoretinopathy, febrile seizures, recessive febrile seizures, dominant febrile seizures, dominant / recessive febrile seizures, choroidal dystrophy, recessive choroidal dystrophy, dominant choroidal dystrophy, central annular choroidal dystrophy, dominant central annular choroidal dystrophy, recessive central annular choroidal dystrophy, epiphyseal dysplasia, recessive epiphyseal dysplasia, dominant epiphyseal dysplasia, multiple epiphyseal dysplasia, recessive multiple epiphyseal dysplasia, dominant multiple epiphyseal dysplasia, ichthyosis, recessive ichthyosis, dominant ichthyosis, quadriplegia and delayed recessive ichthyosis, chorioretinal atrophy, bifocal chorioretinal atrophy, progressive bifocal retinal atrophy Choroidal atrophy, recessive progressive bifocal chorioretinochoroidal atrophy, dominant progressive bifocal chorioretinochoroidal atrophy, Refsum disease, recessive Refsum disease, dominant Refsum disease, adult-onset recessive Refsum disease, infantile recessive Refsum disease, retinal cone dystrophy, recessive retinal cone dystrophy, dominant retinal cone dystrophy, retinal cone dystrophy 1, recessive retinal cone dystrophy 1, dominant retinal cone dystrophy 1, type 3 dichromacy, recessive type 3 dichromacy, dominant type 3 dichromacy, mucopolysaccharidosis, recessive mucopolysaccharidosis, dominant mucopolysaccharidosis, monochromacy Pingelap, recessive monochromacy Pingelap, dominant monochromacy Pingelap, Klippel-Feh Klippel-Veil syndrome, recessive Klippel-Veil syndrome, dominant Klippel-Veil syndrome, microphthalmia, recessive microphthalmia, dominant microphthalmia, limb-girdle muscular dystrophy, recessive limb-girdle muscular dystrophy, dominant limb-girdle muscular dystrophy, short-rib thoracic dysplasia, recessive short-rib thoracic dysplasia, dominant short-rib thoracic dysplasia, polydactyly recessive short-rib thoracic dysplasia, retinal dystrophy recessive short-rib thoracic dysplasia, intellectual disability, trunk obesity, retinal dystrophy, and micropenis (MORM) syndrome, recessive MORM syndrome, dominant MORM syndrome, spasticity and retinal degeneration recessive intellectual disability, Cockayne syndrome, recessive Cockayne syndrome,Cockayne syndrome dominant, congenital retinal nonattachment, recessive nonsyndromic congenital retinal detachment, dominant nonsyndromic congenital retinal detachment, hemolytic anemia, nonspherocytic hemolytic anemia, recessive nonspherocytic hemolytic anemia, dominant nonspherocytic hemolytic anemia, hereditary neuropathy, hereditary neuropathy (Russe type), recessive hereditary neuropathy (Russe type), dominant hereditary neuropathy (Russe type), choroidal sclerosis, recessive choroidal sclerosis, dominant choroidal sclerosis, retinopathy, recessive retinopathy, dominant retinopathy, combined dominant and recessive retinopathy, diffuse dominant retinopathy, variability (varia ble) Dominant retinopathy, diffuse and variable dominant retinopathy, microcephaly, recessive microcephaly, dominant microcephaly, lymphedema dominant microcephaly, chorioretinopathy dominant microcephaly, lymphedema and chorioretinopathy dominant microcephaly, chorioretinopathy, recessive chorioretinopathy, dominant chorioretinopathy, chorioretinopathy and microcephaly, recessive chorioretinopathy and microcephaly, dominant chorioretinopathy and microcephaly, renal coloboma syndrome, recessive renal coloboma syndrome, dominant renal coloboma syndrome, asymptomatic hearing loss, recessive asymptomatic hearing loss, dominant asymptomatic hearing loss, gyroretinal atrophy, recessive gyroretinal atrophy, dominant gyroretinal atrophy, gyroretinal choroidal atrophy Vitreoretinopathy, exudative vitreoretinopathy, familial exudative vitreoretinopathy, recessive familial exudative vitreoretinopathy, dominant familial exudative vitreoretinopathy, dominant familial exudative vitreoretinopathy and Coats disease, neovascular inflammatory vitreoretinopathy, recessive neovascular inflammatory vitreoretinopathy, dominant neovascular inflammatory vitreoretinopathy, focal atrophy, recessive focal atrophy, dominant focal atrophy, Meckel syndrome, recessive Meckel syndrome, dominant Meckel syndrome, vitreoretinopathy, recessive vitreoretinopathy, dominant vitreoretinopathy, bestrophinosis, recessive bestrophinosis, dominant bestrophin Disorder, high bone mass trait, recessive high bone mass trait, dominant high bone mass trait, osteoporosis-pseudoglioma syndrome, recessive osteoporosis-pseudoglioma syndrome, dominant osteoporosis-pseudoglioma syndrome, microphthalmia, recessive microphthalmia, dominant microphthalmia, retinal disease syndrome, recessive retinal disease syndrome, dominant retinal disease syndrome, microphthalmia and retinal disease syndrome, recessive microphthalmia and retinal disease syndrome, dominant microphthalmia and retinal disease syndrome, true microphthalmia, recessive true microphthalmia, dominant true microphthalmia, osteogenesis imperfecta, recessive osteogenesis imperfecta, dominant osteogenesis imperfecta, developmental disorders, osteoarthritis and symptomatic disorders, caudal optic disc malformation,Recessive cavitary optic disc malformation, dominant cavitary optic disc malformation, pitted retina, recessive pitted retina, dominant pitted retina, mevalonic aciduria, recessive mevalonic aciduria, dominant mevalonic aciduria, hyper-IgD syndrome, recessive hyper-IgD syndrome, dominant hyper-IgD syndrome, spastic paraplegia, recessive spastic paraplegia, dominant spastic paraplegia, neuropathy, recessive spastic paraplegia, optic nerve atrophy, recessive spastic paraplegia, neuropathy and optic nerve atrophy, recessive spastic paraplegia (dementia), recessive dementia, dominant dementia, familial dominant dementia, retinoblastoma, recessive retinoblastoma, dominant retinoblastoma, germline retinoblastoma, somatic retinoblastoma, dominant germline or somatic retinoblastoma, retinoblastoma, benign retinoblastoma, pineal gland, osteosarcoma, rod monochromatic vision (rod Monochromacy), recessive rod monochromacy, dominant rod monochromacy, monochromacy, recessive monochromacy, dominant monochromacy, rod monochromacy, rod recessive monochromacy, rod dominant monochromacy, recessive rod monochromacy or monochromacy, pattern dystrophy, recessive pattern dystrophy, dominant pattern dystrophy, S cone syndrome, reinforced S cone syndrome (ESC), recessive ESC, dominant ESC, Goldmann-Fabre syndrome, recessive Goldmann-Fabre syndrome, dominant Goldmann-Fabre syndrome, Bosniadystrophy, recessive Bosniadystrophy, dominant Bosniadystrophy, white punctate retinitis, recessive white punctate retinitis, dominant white punctate retinitis, mucolipidosis IIIγ, recessive mucolipidosis IIIγ, dominant mucolipidosis IIIγ, Meinzer-Sardino syndrome, recessive Meinzer-Sardino Knobloch syndrome, dominant Meinsersardino syndrome, pseudoxanthoma elastica, recessive pseudoxanthoma elastica, dominant pseudoxanthoma elastica, Knobloch syndrome, recessive Knobloch syndrome, dominant Knobloch syndrome, foveal hypoplasia, recessive foveal hypoplasia, dominant foveal hypoplasia, anterior segment malformation, recessive anterior segment malformation, dominant anterior segment malformation, foveal hypoplasia and anterior segment malformation, recessive foveal hypoplasia and anterior segment malformation, dominant foveal hypoplasia and anterior segment malformation, spastic ataxia, recessive spastic ataxia, dominant spastic ataxia, de Grouchy syndrome, Boucher-Neuhauser syndrome, recessive Boucher-Neuhauser syndrome, dominant Boucher-Neuhauser syndrome, Boucher-Neuhauser syndrome with chorioretinal dystrophy, recessive Boucher-Neuhauser syndrome with chorioretinal dystrophy,Dominant Boucher-Neuhauser syndrome with chorioretinal dystrophy, hypoprebetalipoproteinemia, polyacanthocytosis, retinitis pigmentosa, and globus pallidus (HARP) degeneration, recessive HARP degeneration, dominant HARP degeneration, Haller-Folden-Spatz syndrome, recessive Haller-Folden-Spatz syndrome, dominant Haller-Folden-Spatz syndrome, Alagille syndrome, recessive Alagille syndrome, dominant Alagille syndrome, polyneuropathy, hearing loss, ataxia, retinitis pigmentosa and early-onset cataract (PHARC), recessive PHARC, dominant PHARC, recessive symptomatic PHARC, Sausby's retinal degeneration, recessive Sausby's retinal degeneration, dominant Sausby's retinal degeneration, vitreoretinal dystrophy, recessive vitreoretinal dystrophy, dominant vitreoretinal dystrophy, optic neuropathy, recessive optic neuropathy, dominant optic neuropathy, late-onset dominant optic neuropathy, mouth-face-finger syndrome 1, Simpson-Goravi-Boehmel syndrome 2, X-linked retinoschisis, X-linked Oregon eye disease, X-linked optic nerve atrophy, retinal dysplasia, recessive retinal dysplasia, dominant retinal dysplasia, X-linked retinal dysplasia, primary X-linked retinal dysplasia, X-linked Norie's disease, Coats' disease, X-linked Orlando Island eye Diseases, autoimmune inner ear disease (AIED), AIED-like disease, colloideremia, X-linked colloideremia, neuropathy, optic nerve atrophy, hearing loss and retinitis pigmentosa, X-linked neuropathy, optic nerve atrophy, hearing loss and retinitis pigmentosa, X-linked blue cone monochromacy, X-linked type 1 trichromacy and rare macular dystrophy in blue cone monochromacy (BCM), X-linked type 2 trichromacy and rare macular dystrophy in blue cone monochromacy (BCM), mitochondrial Kearns-Sayer syndrome including retinitis pigmentosa, Leigh syndrome, retinopathy, mitochondrial pigmented retina Symptoms and sensorineural hearing loss, albinism, oculocutaneous albinism, neuronal ceroid lipofuscinosis, Zellweger spectrum disorder, cobalamin C deficiency, blue cone monochromacy, hereditary red-green color blindness, type 3 color blindness and yellow-blue abnormalities, latitudinal vision, delayed cone adaptation, uveitis, diabetic retinopathy, diabetic macular edema, persistent corneal epithelial defects, neurotrophic keratitis, herpes interstitial keratitis, chronic dry eye, glaucoma, ocular detachment, ocular blister formation, ocular scarring, visual impairment, blindness, corneal blindness, and dry eye diseases, tear-deficient dry eye diseases, Sjögren's syndrome-associated tear-deficient dry eye diseases,Non-Sjögren's syndrome-related dry eye disease, evaporative dry eye disease, meibomian gland dysfunction, blepharitis, blepharitis, ocular rosacea and atopic dermatitis, tear-deficient and evaporative dry eye disease, Fuchs dystrophy, Fuchs corneal endothelial dystrophy (FECD), Fuchs endothelial dystrophy (FED), panuveitis, diffuse uveitis, panuveitis, cataract, partial cataract, complete cataract, sedentary cataract, progressive cataract, hard cataract, soft cataract, nuclear cataract, nuclear sclerosis cataract, cortical cataract, posterior subcapsular cataract, congenital cataract, corneal dystrophy, epithelial and subepithelial dystrophy, epithelial basement membrane dystrophy, epithelial recurrent erosive dystrophy (Franschetti corneal dystrophy, Dystrophia smolandiensis (Dystrophia) Smolandiensis), and / or Dystrophia Helsinglandica), subepithelial mucinous corneal dystrophy, Miesmann corneal dystrophy, Risch epithelial corneal dystrophy, gelatinous drop-like corneal dystrophy, Bowman layer dystrophy, Reiss-Bücklers corneal dystrophy, Thiel-Benkhe corneal dystrophy, stromal dystrophy-TGFB1 corneal dystrophy, lattice corneal dystrophy, type 1 variant of lattice corneal dystrophy (III, IIIA, I / IIIA, IV), granular corneal dystrophy type 1, granular corneal dystrophy type 2, stromal dystrophy, maculoplasty corneal dystrophy, Schneider crystalline corneal dystrophy, congenital stromal corneal dystrophy, Fleck's dystrophy, posterior amorphous corneal dystrophy, François central cloudy dystrophy Francois), pre-Descemet's corneal dystrophy, endothelial dystrophy, Fuchs' dystrophy, posterior polymorphic corneal dystrophy, congenital hereditary endothelial dystrophy, X-linked corneal endothelial dystrophy, superficial dystrophy, epithelial basement membrane dystrophy, Miesmann's juvenile corneal epithelial dystrophy, gelatinous drop-like corneal dystrophy, Risch's epithelial corneal dystrophy, subepithelial mucinous corneal dystrophy, Reiss-Bücklers corneal dystrophy, Thiel-Benkhe dystrophy, stromal dystrophy,A herpesvirus according to any one of claims 42 to 49 or a pharmaceutical composition according to any one of claims 50 to 57, selected from the group consisting of lattice corneal dystrophy, granular corneal dystrophy, macular corneal dystrophy, Schneider crystalline corneal dystrophy, congenital stromal corneal dystrophy, Fleck's dystrophy, posterior dystrophy, Fuchs' dystrophy, posterior polymorphic corneal dystrophy, congenital hereditary endothelial dystrophy, keratopathy, corneal keratopathy, and calcific corneal keratopathy, for use in treatment.

60. The herpesvirus or pharmaceutical composition according to claim 59, wherein the aforementioned eye condition or disease is neurotrophic keratitis, Stargardt disease, or Leber's congenital amaurosis.

61. The herpesvirus or pharmaceutical composition according to claim 59 or claim 60, wherein the eye condition or disease is neurotrophic keratitis.

62. The herpes virus or pharmaceutical composition according to claim 59 or 60, wherein the eye condition or disease is Stargardt disease.

63. The herpesvirus or pharmaceutical composition according to claim 59 or 60, wherein the eye condition or disease is Leber's congenital amaurosis.

64. Use of a herpesvirus according to any one of claims 42 to 49 or a pharmaceutical composition according to any one of claims 50 to 57 in the manufacture of a medicament for an eye condition or disease.

65. The aforementioned eye condition or disease is retinitis pigmentosa, recessive retinitis pigmentosa, severe recessive retinitis pigmentosa, dominant retinitis pigmentosa, dominant retinitis pigmentosa with choroidal lesions, recessive retinitis pigmentosa with parapetiolar preservation of RPE (PPRPE), recessive retinitis pigmentosa with posterior column ataxia (PCARP), recessive retinitis pigmentosa with microcytosis, symptomatic recessive retinitis pigmentosa, recessive symptomatic disease with retinitis pigmentosa, non-symptomatic recessive retinitis pigmentosa, non-symptomatic dominant retinitis pigmentosa, symptomatic dominant retinitis pigmentosa, juvenile recessive retinitis pigmentosa, recessive retinitis pigmentosa, and intellectual disability, recessive retinitis pigmentosa with macular degeneration. Severe early-onset recessive retinitis pigmentosa, recessive retinitis pigmentosa with bone malformations, recessive retinitis pigmentosa with skeletal abnormalities, dominant retinitis pigmentosa with sensorineural hearing loss, recessive retinitis pigmentosa with hearing loss, recessive retinitis pigmentosa with hearing loss and additional disability, recessive retinitis pigmentosa with vitreous degeneration, early-onset recessive retinitis pigmentosa with macular defect, X-linked retinitis pigmentosa, recessive X-linked retinitis pigmentosa, dominant X-linked retinitis pigmentosa, severe X-linked retinitis pigmentosa, X-linked retinitis pigmentosa with intellectual disability, X-linked retinitis pigmentosa with myopathy, Valday-Beedle-like retinitis pigmentosa, Valday - Beadle-like recessive retinitis pigmentosa, bigenic retinitis pigmentosa, bigenic retinitis pigmentosa with retinal outer segment membrane protein 1, bigenic retinitis pigmentosa with PRPH2, recessive retinitis pigmentosa with early macular lesions, recessive hearing loss without retinitis pigmentosa, recessive congenital hearing loss without retinitis pigmentosa, recessive retinitis pigmentosa and recessive ataxia, recessive retinitis pigmentosa and dominant ataxia, mitochondrial retinitis pigmentosa, mitochondrial retinitis pigmentosa with developmental and neurological abnormalities, mitochondrial retinitis pigmentosa with progressive sensorineural hearing loss, mitochondrial retinitis with hearing loss and neurological abnormalities Pigmentous degeneration, autosomal dominant retinitis pigmentosa, asymptomatic autosomal dominant retinitis pigmentosa, autosomal recessive retinitis pigmentosa, asymptomatic autosomal recessive retinitis pigmentosa, retinal pigment epithelium (RPE), recessive RPE, dominant RPE, recessive RPE degeneration, dominant RPE degeneration, ataxia, recessive ataxia, dominant ataxia, Senior-Loken syndrome, recessive Senior-Loken syndrome, dominant Senior-Loken syndrome, nephronoplasia, recessive nephronoplasia, dominant nephronoplasia, adolescent recessive nephronoplasia, ciliopathy-associated recessive nephronoplasia, juvenile nephronoplasia, juvenile recessive nephronoplasia, juvenile dominant nephronoplasia, Usher syndrome,Usher syndrome type I, Usher syndrome type II, Usher syndrome type III, recessive Usher syndrome, atypical recessive Usher syndrome, dominant Usher syndrome, type 2 recessive Usher syndrome, type 2a recessive Usher syndrome, type 3 recessive Usher syndrome, type 3-like recessive Usher syndrome, atypical recessive Usher syndrome, type 1 recessive Usher syndrome, type 1b recessive Usher syndrome, type 1d recessive Usher syndrome, type 1f recessive Usher syndrome, type 1J recessive Usher syndrome, type 1k recessive Usher syndrome, dizygotic Usher syndrome with CDH23, P Usher syndrome with CDH15 (bigenic), Acadian recessive Usher syndrome, Recessive atypical Usher syndrome (USH3-like), Leber's congenital amaranthosis, Recessive Leber's congenital amaranthosis, Dominant Leber's congenital amaranthosis, De novo Leber's congenital amaranthosis, Dominant Leber's congenital amaranthosis with pituitary dysfunction, Recessive Leber's congenital amaranthosis with myopathy, Recessive Leber's congenital amaranthosis with severe childhood retinal dystrophy, Mitochondrial Leber hereditary optic neuropathy, Leber's hereditary optic neuropathy, Optic nerve atrophy, Recessive optic nerve atrophy, Dominant optic nerve atrophy, Accompanied by ataxia Optic atrophy, recessive optic atrophy with ataxia, dominant optic atrophy with ataxia, recessive optic atrophy with ataxia and 3-methylglutaconic aciduria, dominant optic atrophy with cataract, ataxia and anreflexia, Kaer-type dominant optic atrophy, dominant optic atrophy with sensorineural hearing loss, recessive cerebellar degeneration with optic atrophy, optic atrophy with anesthesia-dystonia syndrome, X-linked optic atrophy with anesthesia-dystonia syndrome, retinal dystrophy, recessive retinal dystrophy, dominant retinal dystrophy, hereditary retinal dystrophy, early-onset recessive retinal dystrophy, recessive disease Symptomatic retinal dystrophy, recessive asymptomatic retinal dystrophy, recessive symptomatic and asymptomatic retinal dystrophy, recessive optic atrophy and retinal dystrophy, recessive retinal dystrophy and obesity, recessive retinal dystrophy and cerebellar dysplasia, symptomatic recessive optic atrophy and retinal dystrophy, dominant retinal dystrophy with iris defects, ciliopathy spectrum including retinal dystrophy, recessive ciliopathy spectrum including retinal dystrophy, dominant ciliopathy spectrum including retinal dystrophy, dominant optic atrophy with neuropathy and myopathy,Dominant optic atrophy with intellectual disability and developmental delay, symptomatic optic atrophy, asymptomatic optic atrophy, recessive asymptomatic optic atrophy, dominant asymptomatic optic atrophy, recessive symptomatic optic atrophy, dominant symptomatic optic atrophy, Charcot-Marie-Tooth disease, recessive Charcot-Marie-Tooth disease, dominant Charcot-Marie-Tooth disease, benign spotted retina, recessive benign spotted retina, dominant benign spotted retina, symptomatic retinopathy, recessive symptomatic retinopathy, dominant symptomatic retinopathy, Batten disease, recessive Batten disease, dominant Batten disease, recessive Batten disease (neuroceroid lipofuscinosis type 3), juvenile recessive Batten disease (neuroceroid lipofuscinosis type 3) Ceroid lipofuscinosis type 3), neuronal ceroid lipofuscinosis, recessive neuronal ceroid lipofuscinosis, recessive neuronal ceroid lipofuscinosis type 1, dominant neuronal ceroid lipofuscinosis, Stargart disease, recessive Stargart disease, dominant Stargart disease, juvenile Stargart disease, late-onset Stargart disease, Stargart-like macular dystrophy, recessive Stargart-like macular dystrophy, dominant Stargart-like macular dystrophy, macular dystrophy, recessive macular dystrophy, early-onset macular dystrophy, adult-onset macular dystrophy, early-onset recessive macular dystrophy Stroke, adult-onset recessive macular dystrophy, early adult-onset recessive macular dystrophy, juvenile recessive macular dystrophy with hypotrichosis, dominant macular dystrophy, late-onset dominant macular dystrophy, dominant macular dystrophy with lens zonules, bullseye dominant macular dystrophy, butterfly-shaped dominant macular dystrophy, age-related dominant macular dystrophy, benign concentric annular dominant macular dystrophy, vitelloid recessive macular dystrophy, vitelloid dominant macular dystrophy, atypical vitelloid dominant macular dystrophy, dominant adult-type vitelloid macular dystrophy, Stargard-like dominant Macular dystrophy, Stargard-type dominant macular dystrophy, North Carolina-type dominant macular dystrophy, North Carolina-like dominant macular dystrophy, North Carolina-like dominant macular dystrophy with progressive sensorineural hearing loss, cystoid dominant macular dystrophy, Best-type dominant macular dystrophy, occult macular dystrophy, recessive occult macular dystrophy, dominant occult macular dystrophy, age-related familial macular dystrophy, X-linked atrophic macular dystrophy, recessive X-linked atrophic macular dystrophy, dominant X-linked atrophic macular dystrophy,Mitochondrial macular pattern dystrophy with type II diabetes and hearing loss, macular dystrophy, recessive macular dystrophy, dominant macular dystrophy, rod dystrophy, recessive rod dystrophy, dominant rod dystrophy, cone dystrophy, recessive cone dystrophy, dominant cone dystrophy, recessive cone dystrophy with supernormal rod electroretinogram, early-onset recessive cone dystrophy, late-onset recessive cone dystrophy, cone dystrophy 1, X-linked cone dystrophy 1, cone dystrophy 2, progressive cone dystrophy 2, X-linked progressive cone dystrophy 2 Delayed cone adaptation, recessive delayed cone adaptation, dominant delayed cone adaptation, cone-rod dystrophy, recessive cone-rod dystrophy, dominant cone-rod dystrophy, isolated cone-rod dystrophy, progressive cone-rod dystrophy, X-linked cone-rod dystrophy, X-linked progressive cone-rod dystrophy, progressive dominant cone-rod dystrophy, cone-rod dystrophy and enamel hypoplasia syndrome, recessive cone-rod dystrophy and enamel hypoplasia syndrome, dominant cone-rod dystrophy and enamel hypoplasia syndrome, recessive cone-rod with internal retinopathy Rod-rod dystrophy, recessive pyramidal-rod dystrophy with bone disease, congenital symptomatic non-progressive recessive pyramidal-rod dystrophy, recessive pyramidal-rod dystrophy with hearing loss, recessive pyramidal-rod dystrophy with psychomotor retardation, recessive pyramidal and pyramidal-rod dystrophy, pyramidal-rod synaptic disease, congenital pyramidal-rod synaptic disease, recessive congenital pyramidal-rod synaptic disease, dominant congenital pyramidal-rod synaptic disease, rod-pyramidal dystrophy, recessive rod-pyramidal dystrophy, dominant rod-pyramidal dystrophy, early-onset recessive rod-pyramidal dystrophy, non-symptomatic recessive rod-pyramidal dystrophy, recessive neodystrophy Fundland rod-cone dystrophy, recessive progressive cone dystrophy, Stickler syndrome, dominant Stickler syndrome, recessive Stickler syndrome, dominant Stickler syndrome type I, dominant Stickler syndrome type II, Marshall syndrome, dominant Marshall syndrome, recessive Marshall syndrome, monochromacy, recessive monochromacy, dominant monochromacy, recessive complete monochromacy, recessive incomplete monochromacy, macular degeneration, age-related macular degeneration, complex etiology age-related macular degeneration, isolated age-related macular degeneration, wet age-related macular degeneration, dry age-related macular degeneration, drusen, recessive drusen, dominant drusen,Early-onset recessive drusen, early-onset dominant drusen, macular drusen, dominant radial macular drusen, pigmentary paravenous retinal choroidal atrophy, recessive pigmentary paravenous retinal choroidal atrophy, dominant pigmentary paravenous retinal choroidal atrophy, progressive bifocal retinal choroidal atrophy, Valday-Beedl syndrome, recessive Valday-Beedl syndrome, dominant Valday-Beedl syndrome, recessive Valday-Beedl syndrome with developmental abnormalities, retinal degeneration, recessive retinal degeneration, dominant retinal degeneration, non-symptomatic recessive retinal degeneration, Doynn's honeycomb retinal degeneration, Doynn's recessive honeycomb retinal degeneration, Doynn's dominant honeycomb retinal degeneration (Malattiya) Leventinese), recessive nephronoplasia with retinal degeneration, Alström syndrome, recessive Alström syndrome, dominant Alström syndrome, Joubert syndrome, recessive Joubert syndrome, dominant Joubert syndrome, Joubert syndrome, recessive Joubert syndrome, dominant Joubert syndrome, X-linked Joubert syndrome, vitreoretinal degeneration, recessive vitreoretinal degeneration, dominant vitreoretinal degeneration, snowflake vitreoretinal degeneration, snowflake Rake-dominant vitreoretinal degeneration, small mouth disease, recessive small mouth disease, dominant small mouth disease, night blindness, stop night blindness, congenital night blindness, congenital stop night blindness, severe congenital stop night blindness, recessive congenital stop night blindness, recessive complete congenital stop night blindness, dominant Congenital arresting night blindness, Nougarette type dominant congenital arresting night blindness, small-mouth type recessive congenital stopping night blindness, Riggs type recessive congenital stopping night blindness, Schubert-Bornschein type recessive congenital stopping night blindness, white-punctate fundus type recessive congenital stopping night blindness Retinal night blindness, complete recessive congenital stasis, X-linked congenital stasis, incomplete X-linked congenital stasis, retinal vascular disease, cerebral leukodystrophy, retinal vascular disease with cerebral leukodystrophy, recessive retinal vascular disease with cerebral leukodystrophy, dominant retinal vascular disease with cerebral leukodystrophy, Eicardi-Gutierre syndrome, Eicardi-Gutierre syndrome 1, recessive Eicardi-Gutierre syndrome 1, dominant Aicardi-Uthier syndrome 1, lupus frostbite, recessive lupus frostbite, dominant lupus frostbite, Martinique retinal dystrophy and retinitis pigmentosa, recessive Martinique retinal dystrophy and retinitis pigmentosa, dominant Martinique retinal dystrophy and retinitis pigmentosa, spinocerebellar ataxia, recessive spinocerebellar ataxia, dominant spinocerebellar ataxia, spinocerebellar ataxia with macular dystrophy, spinocerebellar ataxia with retinal degeneration,Spinocerebellar ataxia with macular dystrophy or retinal degeneration, recessive spinocerebellar ataxia with macular dystrophy or retinal degeneration, dominant spinocerebellar ataxia with macular dystrophy or retinal degeneration, Wolfram syndrome, recessive Wolfram syndrome, dominant Wolfram syndrome, low-frequency sensorineural hearing loss, recessive low-frequency sensorineural hearing loss, dominant low-frequency sensorineural hearing loss, ophthalmo-ot syndrome, recessive ophthalmo-ot syndrome, dominant ophthalmo-ot syndrome, recessive kidney, skeletal and retinal abnormalities, recessive abetalipoproteinemia, microcephaly, recessive microcephaly, dominant microcephaly, growth disorders and recessive retinopathy. Cervical dystrophy, Vietti crystalline corneal-retinal dystrophy, recessive Vietti crystalline corneal-retinal dystrophy, dominant Vietti crystalline corneal-retinal dystrophy, Wagner's disease, erosive vitreoretinopathy, Wagner's disease and erosive vitreoretinopathy, recessive Wagner's disease and erosive vitreoretinopathy, dominant Wagner's disease and erosive vitreoretinopathy, febrile seizures, recessive febrile seizures, dominant febrile seizures, dominant / recessive febrile seizures, choroidal dystrophy, recessive choroidal dystrophy, dominant choroidal dystrophy, centrally ring-shaped choroidal dystrophy, dominant centrally ring-shaped choroidal dystrophy Recessive central symmetry chorioretinoid dystrophy, epiphyseal dysplasia, recessive epiphyseal dysplasia, dominant epiphyseal dysplasia, multiple epiphyseal dysplasia, recessive multiple epiphyseal dysplasia, dominant multiple epiphyseal dysplasia, ichthyosis, recessive ichthyosis, dominant ichthyosis, quadriplegia and delayed recessive ichthyosis, chorioretinal atrophy, bifocal chorioretinal atrophy, progressive bifocal chorioretinal atrophy, recessive progressive bifocal chorioretinal atrophy, dominant progressive bifocal chorioretinal atrophy, Refsum disease, recessive Refsum disease, dominant Refsum disease, adult-type recessive Refsum disease, infant-type recessive Refsum disease, retinal cone dystrophy, recessive retinal cone dystrophy, dominant retinal cone dystrophy strophy, retinal cone dystrophy 1, recessive retinal cone dystrophy 1, dominant retinal cone dystrophy 1, type 3 dichromacy, recessive type 3 dichromacy, dominant type 3 dichromacy, mucopolysaccharidosis, recessive mucopolysaccharidosis, dominant mucopolysaccharidosis, monochromacy Pingelap, recessive monochromacy Pingelap, dominant monochromacy Pingelap, Klippel-Feuer syndrome, recessive Klippel-Feuer syndrome, dominant Klippel-Feuer syndrome, microphthalmia, recessive microphthalmia, dominant microphthalmia, limb-girdle muscular dystrophy, recessive limb-girdle muscular dystrophy, dominant limb-girdle muscular dystrophy, short-rib thoracic dysplasia, recessive short-rib thoracic dysplasia Thoracic dysplasia, dominant short-rib thoracic dysplasia, polydactyly recessive short-rib thoracic dysplasia, retinal dystrophy recessive short-rib thoracic dysplasia, intellectual disability, trunk obesity, retinal dystrophy, and micropenis (MORM) syndrome, recessive MORM syndrome, dominant MORM syndrome, spasticity and retinal degeneration recessive intellectual disability, Cockayne syndrome, recessive Cockayne syndrome, dominant Cockayne syndrome, congenital retinal detachment, recessive non-syndromic congenital retinal detachment, dominant non-syndromic congenital retinal detachment, hemolytic anemia, nonspherocytic hemolytic anemia, recessive nonspherocytic hemolytic anemia, dominant nonspherocytic hemolytic anemia, hereditary neuropathy,Hereditary neuropathy (Lasse type), recessive hereditary neuropathy (Lasse type), dominant hereditary neuropathy (Lasse type), choroidal sclerosis, recessive choroidal sclerosis, dominant choroidal sclerosis, retinopathy, recessive retinopathy, dominant retinopathy, combined dominant and recessive retinopathy, diffuse dominant retinopathy, variable dominant retinopathy, diffuse and variable dominant retinopathy, microcephaly, recessive microcephaly, dominant microcephaly, lymphedema-dominant microcephaly, chorioretinopathy-dominant microcephaly, lymphedema- and chorioretinopathy-dominant microcephaly, chorioretinopathy, recessive chorioretinopathy, dominant chorioretinopathy, chorioretinopathy and microcephaly, recessive chorioretinopathy and micro Microcephaly, dominant chorioretinopathy and microcephaly, renal coloboma syndrome, recessive renal coloboma syndrome, dominant renal coloboma syndrome, asymptomatic hearing loss, recessive asymptomatic hearing loss, dominant asymptomatic hearing loss, gyrocephalic atrophy, recessive gyrocephalic atrophy, dominant gyrocephalic atrophy, gyrocephalic retinal choroidal atrophy, vitreoretinopathy, exudative vitreoretinopathy, familial exudative vitreoretinopathy, recessive familial exudative vitreoretinopathy, dominant familial exudative vitreoretinopathy, dominant familial exudative vitreoretinopathy and Coats disease, neovascular inflammatory vitreoretinopathy, recessive neovascular inflammatory vitreoretinopathy, dominant neovascular inflammatory vitreoretinopathy, focal atrophy, recessive Sex-limited focal atrophy, dominant focal atrophy, Meckel syndrome, recessive Meckel syndrome, dominant Meckel syndrome, vitreous-retinal choriolopathy, recessive vitreous-retinal choriolopathy, dominant vitreous-retinal choriolopathy, bestrofin syndrome, recessive bestrofin syndrome, dominant bestrofin syndrome, high bone mass trait, recessive high bone mass trait, dominant high bone mass trait, osteoporosis-pseudoglioma syndrome, recessive osteoporosis-pseudoglioma syndrome, dominant osteoporosis-pseudoglioma syndrome, microphthalmia, recessive microphthalmia, dominant microphthalmia, retinal disease syndrome, recessive retinal disease syndrome, dominant retinal disease syndrome, microphthalmia and retinal disease syndrome, recessive microphthalmia and retinal disease Symptom syndrome, dominant microphthalmia and retinal disease syndrome, true microphthalmia, recessive true microphthalmia, dominant true microphthalmia, osteogenesis imperfecta, recessive osteogenesis imperfecta, dominant osteogenesis imperfecta, developmental disorders, osteoarthritis and symptomatic disorders, caudal optic disc malformation, recessive caudal optic disc malformation, dominant caudal optic disc malformation, white punctate fundus, recessive white punctate fundus, dominant white punctate fundus, mevalonic aciduria, recessive mevalonic aciduria, dominant mevalonic aciduria, hyper-IgD syndrome, recessive hyper-IgD syndrome, dominant hyper-IgD syndrome, spastic paraplegia, recessive spastic paraplegia, dominant spastic paraplegia, neuropathy recessive spastic paraplegia, optic nerve atrophy recessive spastic paraplegia,Neuropathy and optic nerve atrophy, recessive spastic paraplegia (dementia), recessive dementia, dominant dementia, familial dominant dementia, retinoblastoma, recessive retinoblastoma, dominant retinoblastoma, germline retinoblastoma, somatic retinoblastoma, dominant germline or somatic retinoblastoma, retinoblastoma, benign retinoblastoma, pineal gland, osteosarcoma, rod monochromacy, recessive rod monochromacy, dominant rod monochromacy, monochromacy, recessive monochromacy, dominant monochromacy, rod monochromacy, rod recessive monochromacy, rod dominant monochromacy, recessive rod monochromacy or monochromacy, pattern dystrophy, recessive pattern dystrophy, dominant pattern dystrophy S cone syndrome, reinforced S cone syndrome (ESC), recessive ESC, dominant ESC, Goldmann-Fabre syndrome, recessive Goldmann-Fabre syndrome, dominant Goldmann-Fabre syndrome, Bosniadystrophy, recessive Bosniadystrophy, dominant Bosniadystrophy, white punctate retinitis, recessive white punctate retinitis, dominant white punctate retinitis, mucolipidosis IIIγ, recessive mucolipidosis IIIγ, dominant mucolipidosis IIIγ, Mainzer-Sardino syndrome, recessive Mainzer-Sardino syndrome, dominant Mainzer-Sardino syndrome, elastic Fibromic pseudoxanthoma, recessive pseudoxanthoma elastica, dominant pseudoxanthoma elastica, Knobloch syndrome, recessive Knobloch syndrome, dominant Knobloch syndrome, foveal hypoplasia, recessive foveal hypoplasia, dominant foveal hypoplasia, anterior segment malformation, recessive anterior segment malformation, dominant anterior segment malformation, foveal hypoplasia and anterior segment malformation, recessive foveal hypoplasia and anterior segment malformation, dominant foveal hypoplasia and anterior segment malformation, spastic ataxia, recessive spastic ataxia, dominant spastic ataxia, de Grouchy syndrome, Boucher-Neuhauser syndrome, recessive Boucher-Neuhauser syndrome, dominant Boucher-Neuhauser Ihauser syndrome, Boucher-Neuhauser syndrome with chorioretinal dystrophy, recessive Boucher-Neuhauser syndrome with chorioretinal dystrophy, dominant Boucher-Neuhauser syndrome with chorioretinal dystrophy, hypoprebetalipoproteinemia, acanthocyanosis, retinitis pigmentosa, and globus pallidus (HARP) degeneration, recessive HARP degeneration, dominant HARP degeneration, Haller-Folden-Spatz syndrome, recessive Haller-Folden-Spatz syndrome, dominant Haller-Folden-Spatz syndrome, Alagille syndrome, recessive Alagille syndrome, dominant Alagille syndrome,Polyneuropathy, deafness, ataxia, retinitis pigmentosa and early-onset cataract (PHARC), recessive PHARC, dominant PHARC, recessive symptomatic PHARC, Sausby's retinal degeneration, recessive Sausby's retinal degeneration, dominant Sausby's retinal degeneration, vitreoretinal dystrophy, recessive vitreoretinal dystrophy, dominant vitreoretinal dystrophy, optic neuropathy, recessive optic neuropathy, dominant optic neuropathy, late-onset dominant optic neuropathy, mouth-face-finger syndrome1, Simpson-Goravi-Boehmel syndrome2, X-linked retinoschisis, X-linked Oregon eye disease, X-linked optic atrophy, retinal dysplasia, recessive retinoschisis Membrane dysplasia, dominant retinal dysplasia, X-linked retinal dysplasia, primary X-linked retinal dysplasia, X-linked Norie disease, Coats disease, X-linked Åland Island eye disease, autoimmune inner ear disease (AIED), AIED-like disease, colloideremia, X-linked colloideremia, neuropathy, optic nerve atrophy, hearing loss and retinitis pigmentosa, X-linked neuropathy, optic nerve atrophy, hearing loss and retinitis pigmentosa, X-linked blue cone monochromacy, X-linked type 1 trichromacy and rare macular dystrophy in blue cone monochromacy (BCM), X-linked type 2 trichromacy and rare macular dystrophy Trophy, mitochondrial Kearns-Sayer syndrome including retinitis pigmentosa, Leigh syndrome, retinopathy, mitochondrial pigmentary retinopathy and sensorineural hearing loss, albinism, oculocutaneous albinism, neuronal ceroid lipofuscinosis, Zellweger spectrum disorder, cobalamin C deficiency, blue cone monochromacy, hereditary red-green color blindness, type 3 color blindness and yellow-blue abnormalities, strepoptic vision, delayed cone adaptation, uveitis, diabetic retinopathy, diabetic macular edema, persistent corneal epithelial defect, neurotrophic keratitis, herpes interstitial keratitis, chronic dry eye, glaucoma, ocular detachment, ocular blister formation, ocular scarring, visual impairment, loss of vision. Brightness, corneal blindness, dry eye disease, tear-deficient dry eye disease, Sjögren's syndrome-related tear-deficient dry eye disease, non-Sjögren's syndrome-related dry eye disease, evaporative dry eye disease, meibomian gland dysfunction, blepharitis, blepharitis, ocular rosacea and atopic dermatitis, tear-deficient and evaporative dry eye diseases, Fuchs dystrophy, Fuchs corneal endothelial dystrophy (FECD), Fuchs endothelial dystrophy (FED), panuveitis, diffuse uveitis, panuveitis, cataract, partial cataract, complete cataract, sedentary cataract, progressive cataract, hard cataract,Soft cataracts, nuclear cataracts, nuclear sclerotic cataracts, cortical cataracts, posterior subcapsular cataracts, congenital cataracts, corneal dystrophy, epithelial and subepithelial dystrophy, epithelial basement membrane dystrophy, epithelial recurrent erosive dystrophy (Franschetty corneal dystrophy, Dystrophia smolandiensis, and / or Dystrophia helsinglandica, subepithelial mucinous corneal dystrophy, Miesmann corneal dystrophy, Risch epithelial corneal dystrophy, gelatinous drop-like corneal dystrophy, Bowman's layer dystrophy) Rophy, Reis-Bücklers corneal dystrophy, Thiel-Benkhe corneal dystrophy, stromal dystrophy-TGFB1 corneal dystrophy, lattice corneal dystrophy, type 1 variant of lattice corneal dystrophy (III, IIIA, I / IIIA, IV), granular corneal dystrophy type 1, granular corneal dystrophy type 2, stromal dystrophy, macular corneal dystrophy, Schneider crystalline corneal dystrophy, congenital stromal corneal dystrophy, Fleck's dystrophy Posterior amorphous corneal dystrophy, François central cloud dystrophy, anterior Descemet's membrane corneal dystrophy, endothelial dystrophy, Fuchs dystrophy, posterior polymorphic corneal dystrophy, congenital hereditary endothelial dystrophy, X-linked corneal endothelial dystrophy, superficial dystrophy, epithelial basement membrane dystrophy, Miesmann juvenile corneal epithelial dystrophy, gelatinous drop-like corneal dystrophy, Risch epithelial corneal dystrophy, subepithelial mucinous corneal dystrophy, Reiss-Bücklers corneal dystrophy The use according to claim 64, selected from the group consisting of trophy, Thiel-Benkez dystrophy, stromal dystrophy, lattice corneal dystrophy, granular corneal dystrophy, maculoplasty, Schneider crystalline corneal dystrophy, congenital stromal corneal dystrophy, Fleck's dystrophy, posterior dystrophy, Fuchs dystrophy, posterior polymorphic corneal dystrophy, congenital hereditary endothelial dystrophy, keratopathy, keratopathy, corneal keratopathy, and calcific keratopathy.

66. The use according to claim 64 or 65, wherein the eye condition or disease is neurotrophic keratitis, Stargardt disease, or Leber's congenital amaurosis.

67. The use according to any one of claims 64 to 66, wherein the eye condition or disease is neurotrophic keratitis.

68. The use according to any one of claims 64 to 66, wherein the aforementioned eye condition or disease is Stargardt disease.

69. The use according to any one of claims 64 to 66, wherein the eye condition or disease is Leber's congenital amaurosis.

70. A method for expressing, enhancing, increasing, strengthening, and / or supplementing the level of polypeptide in one or more cells of an eye of a subject, comprising administering to the subject an effective amount of the herpesvirus described in any one of claims 42 to 49 or the pharmaceutical composition described in any one of claims 50 to 57.

71. The method according to claim 70, wherein the one or more cells are one or more corneal epithelial cells, rod cells, cone cells, photoreceptors, retinal pigment epithelial cells, retinal ganglion cells, bipolar cells, horizontal cells, Müller cells, or axon-free cells.

72. A method for providing preventive, mitigating, or therapeutic relief of one or more signs or symptoms of an eye condition or disease in a subject in need, comprising administering to the subject an effective amount of the herpes virus described in any one of claims 42 to 49 or the pharmaceutical composition described in any one of claims 50 to 57.

73. A method for treating an eye condition or disease in a subject in need, comprising administering to the subject an effective amount of the herpes virus described in any one of claims 42 to 49 or the pharmaceutical composition described in any one of claims 50 to 57.

74. The aforementioned eye condition or disease is retinitis pigmentosa, recessive retinitis pigmentosa, severe recessive retinitis pigmentosa, dominant retinitis pigmentosa, dominant retinitis pigmentosa with choroidal lesions, recessive retinitis pigmentosa with parapetiolar preservation of RPE (PPRPE), recessive retinitis pigmentosa with posterior column ataxia (PCARP), recessive retinitis pigmentosa with microcytosis, symptomatic recessive retinitis pigmentosa, recessive symptomatic disease with retinitis pigmentosa, non-symptomatic recessive retinitis pigmentosa, non-symptomatic dominant retinitis pigmentosa, symptomatic dominant retinitis pigmentosa, juvenile recessive retinitis pigmentosa, recessive retinitis pigmentosa, and intellectual disability, recessive retinitis pigmentosa with macular degeneration. Severe early-onset recessive retinitis pigmentosa, recessive retinitis pigmentosa with bone malformations, recessive retinitis pigmentosa with skeletal abnormalities, dominant retinitis pigmentosa with sensorineural hearing loss, recessive retinitis pigmentosa with hearing loss, recessive retinitis pigmentosa with hearing loss and additional disability, recessive retinitis pigmentosa with vitreous degeneration, early-onset recessive retinitis pigmentosa with macular defect, X-linked retinitis pigmentosa, recessive X-linked retinitis pigmentosa, dominant X-linked retinitis pigmentosa, severe X-linked retinitis pigmentosa, X-linked retinitis pigmentosa with intellectual disability, X-linked retinitis pigmentosa with myopathy, Valday-Beedle-like retinitis pigmentosa, Valday - Beadle-like recessive retinitis pigmentosa, bigenic retinitis pigmentosa, bigenic retinitis pigmentosa with retinal outer segment membrane protein 1, bigenic retinitis pigmentosa with PRPH2, recessive retinitis pigmentosa with early macular lesions, recessive hearing loss without retinitis pigmentosa, recessive congenital hearing loss without retinitis pigmentosa, recessive retinitis pigmentosa and recessive ataxia, recessive retinitis pigmentosa and dominant ataxia, mitochondrial retinitis pigmentosa, mitochondrial retinitis pigmentosa with developmental and neurological abnormalities, mitochondrial retinitis pigmentosa with progressive sensorineural hearing loss, mitochondrial retinitis with hearing loss and neurological abnormalities Pigmentous degeneration, autosomal dominant retinitis pigmentosa, asymptomatic autosomal dominant retinitis pigmentosa, autosomal recessive retinitis pigmentosa, asymptomatic autosomal recessive retinitis pigmentosa, retinal pigment epithelium (RPE), recessive RPE, dominant RPE, recessive RPE degeneration, dominant RPE degeneration, ataxia, recessive ataxia, dominant ataxia, Senior-Loken syndrome, recessive Senior-Loken syndrome, dominant Senior-Loken syndrome, nephronoplasia, recessive nephronoplasia, dominant nephronoplasia, adolescent recessive nephronoplasia, ciliopathy-associated recessive nephronoplasia, juvenile nephronoplasia, juvenile recessive nephronoplasia, juvenile dominant nephronoplasia, Usher syndrome,Usher syndrome type I, Usher syndrome type II, Usher syndrome type III, recessive Usher syndrome, atypical recessive Usher syndrome, dominant Usher syndrome, type 2 recessive Usher syndrome, type 2a recessive Usher syndrome, type 3 recessive Usher syndrome, type 3-like recessive Usher syndrome, atypical recessive Usher syndrome, type 1 recessive Usher syndrome, type 1b recessive Usher syndrome, type 1d recessive Usher syndrome, type 1f recessive Usher syndrome, type 1J recessive Usher syndrome, type 1k recessive Usher syndrome, dizygotic Usher syndrome with CDH23, P Usher syndrome with CDH15 (bigenic), Acadian recessive Usher syndrome, Recessive atypical Usher syndrome (USH3-like), Leber's congenital amaranthosis, Recessive Leber's congenital amaranthosis, Dominant Leber's congenital amaranthosis, De novo Leber's congenital amaranthosis, Dominant Leber's congenital amaranthosis with pituitary dysfunction, Recessive Leber's congenital amaranthosis with myopathy, Recessive Leber's congenital amaranthosis with severe childhood retinal dystrophy, Mitochondrial Leber hereditary optic neuropathy, Leber's hereditary optic neuropathy, Optic nerve atrophy, Recessive optic nerve atrophy, Dominant optic nerve atrophy, Accompanied by ataxia Optic atrophy, recessive optic atrophy with ataxia, dominant optic atrophy with ataxia, recessive optic atrophy with ataxia and 3-methylglutaconic aciduria, dominant optic atrophy with cataract, ataxia and anreflexia, Kaer-type dominant optic atrophy, dominant optic atrophy with sensorineural hearing loss, recessive cerebellar degeneration with optic atrophy, optic atrophy with anesthesia-dystonia syndrome, X-linked optic atrophy with anesthesia-dystonia syndrome, retinal dystrophy, recessive retinal dystrophy, dominant retinal dystrophy, hereditary retinal dystrophy, early-onset recessive retinal dystrophy, recessive disease Symptomatic retinal dystrophy, recessive asymptomatic retinal dystrophy, recessive symptomatic and asymptomatic retinal dystrophy, recessive optic atrophy and retinal dystrophy, recessive retinal dystrophy and obesity, recessive retinal dystrophy and cerebellar dysplasia, symptomatic recessive optic atrophy and retinal dystrophy, dominant retinal dystrophy with iris defects, ciliopathy spectrum including retinal dystrophy, recessive ciliopathy spectrum including retinal dystrophy, dominant ciliopathy spectrum including retinal dystrophy, dominant optic atrophy with neuropathy and myopathy,Dominant optic atrophy with intellectual disability and developmental delay, symptomatic optic atrophy, asymptomatic optic atrophy, recessive asymptomatic optic atrophy, dominant asymptomatic optic atrophy, recessive symptomatic optic atrophy, dominant symptomatic optic atrophy, Charcot-Marie-Tooth disease, recessive Charcot-Marie-Tooth disease, dominant Charcot-Marie-Tooth disease, benign spotted retina, recessive benign spotted retina, dominant benign spotted retina, symptomatic retinopathy, recessive symptomatic retinopathy, dominant symptomatic retinopathy, Batten disease, recessive Batten disease, dominant Batten disease, recessive Batten disease (neuroceroid lipofuscinosis type 3), juvenile recessive Batten disease (neuroceroid lipofuscinosis type 3) Ceroid lipofuscinosis type 3), neuronal ceroid lipofuscinosis, recessive neuronal ceroid lipofuscinosis, recessive neuronal ceroid lipofuscinosis type 1, dominant neuronal ceroid lipofuscinosis, Stargart disease, recessive Stargart disease, dominant Stargart disease, juvenile Stargart disease, late-onset Stargart disease, Stargart-like macular dystrophy, recessive Stargart-like macular dystrophy, dominant Stargart-like macular dystrophy, macular dystrophy, recessive macular dystrophy, early-onset macular dystrophy, adult-onset macular dystrophy, early-onset recessive macular dystrophy Stroke, adult-onset recessive macular dystrophy, early adult-onset recessive macular dystrophy, juvenile recessive macular dystrophy with hypotrichosis, dominant macular dystrophy, late-onset dominant macular dystrophy, dominant macular dystrophy with lens zonules, bullseye dominant macular dystrophy, butterfly-shaped dominant macular dystrophy, age-related dominant macular dystrophy, benign concentric annular dominant macular dystrophy, vitelloid recessive macular dystrophy, vitelloid dominant macular dystrophy, atypical vitelloid dominant macular dystrophy, dominant adult-type vitelloid macular dystrophy, Stargard-like dominant Macular dystrophy, Stargard-type dominant macular dystrophy, North Carolina-type dominant macular dystrophy, North Carolina-like dominant macular dystrophy, North Carolina-like dominant macular dystrophy with progressive sensorineural hearing loss, cystoid dominant macular dystrophy, Best-type dominant macular dystrophy, occult macular dystrophy, recessive occult macular dystrophy, dominant occult macular dystrophy, age-related familial macular dystrophy, X-linked atrophic macular dystrophy, recessive X-linked atrophic macular dystrophy, dominant X-linked atrophic macular dystrophy,Mitochondrial macular pattern dystrophy with type II diabetes and hearing loss, macular dystrophy, recessive macular dystrophy, dominant macular dystrophy, rod dystrophy, recessive rod dystrophy, dominant rod dystrophy, cone dystrophy, recessive cone dystrophy, dominant cone dystrophy, recessive cone dystrophy with supernormal rod electroretinogram, early-onset recessive cone dystrophy, late-onset recessive cone dystrophy, cone dystrophy 1, X-linked cone dystrophy 1, cone dystrophy 2, progressive cone dystrophy 2, X-linked progressive cone dystrophy 2 Delayed cone adaptation, recessive delayed cone adaptation, dominant delayed cone adaptation, cone-rod dystrophy, recessive cone-rod dystrophy, dominant cone-rod dystrophy, isolated cone-rod dystrophy, progressive cone-rod dystrophy, X-linked cone-rod dystrophy, X-linked progressive cone-rod dystrophy, progressive dominant cone-rod dystrophy, cone-rod dystrophy and enamel hypoplasia syndrome, recessive cone-rod dystrophy and enamel hypoplasia syndrome, dominant cone-rod dystrophy and enamel hypoplasia syndrome, recessive cone-rod with internal retinopathy Rod-rod dystrophy, recessive pyramidal-rod dystrophy with bone disease, congenital symptomatic non-progressive recessive pyramidal-rod dystrophy, recessive pyramidal-rod dystrophy with hearing loss, recessive pyramidal-rod dystrophy with psychomotor retardation, recessive pyramidal and pyramidal-rod dystrophy, pyramidal-rod synaptic disease, congenital pyramidal-rod synaptic disease, recessive congenital pyramidal-rod synaptic disease, dominant congenital pyramidal-rod synaptic disease, rod-pyramidal dystrophy, recessive rod-pyramidal dystrophy, dominant rod-pyramidal dystrophy, early-onset recessive rod-pyramidal dystrophy, non-symptomatic recessive rod-pyramidal dystrophy, recessive neodystrophy Fundland rod-cone dystrophy, recessive progressive cone dystrophy, Stickler syndrome, dominant Stickler syndrome, recessive Stickler syndrome, dominant Stickler syndrome type I, dominant Stickler syndrome type II, Marshall syndrome, dominant Marshall syndrome, recessive Marshall syndrome, monochromacy, recessive monochromacy, dominant monochromacy, recessive complete monochromacy, recessive incomplete monochromacy, macular degeneration, age-related macular degeneration, complex etiology age-related macular degeneration, isolated age-related macular degeneration, wet age-related macular degeneration, dry age-related macular degeneration, drusen, recessive drusen, dominant drusen,Early-onset recessive drusen, early-onset dominant drusen, macular drusen, dominant radial macular drusen, pigmentary paravenous retinal choroidal atrophy, recessive pigmentary paravenous retinal choroidal atrophy, dominant pigmentary paravenous retinal choroidal atrophy, progressive bifocal retinal choroidal atrophy, Valday-Beedl syndrome, recessive Valday-Beedl syndrome, dominant Valday-Beedl syndrome, recessive Valday-Beedl syndrome with developmental abnormalities, retinal degeneration, recessive retinal degeneration, dominant retinal degeneration, non-symptomatic recessive retinal degeneration, Doynn's honeycomb retinal degeneration, Doynn's recessive honeycomb retinal degeneration, Doynn's dominant honeycomb retinal degeneration (Malattiya) Leventinese), recessive nephronoplasia with retinal degeneration, Alström syndrome, recessive Alström syndrome, dominant Alström syndrome, Joubert syndrome, recessive Joubert syndrome, dominant Joubert syndrome, Joubert syndrome, recessive Joubert syndrome, dominant Joubert syndrome, X-linked Joubert syndrome, vitreoretinal degeneration, recessive vitreoretinal degeneration, dominant vitreoretinal degeneration, snowflake vitreoretinal degeneration, snowflake Rake-dominant vitreoretinal degeneration, small mouth disease, recessive small mouth disease, dominant small mouth disease, night blindness, stop night blindness, congenital night blindness, congenital stop night blindness, severe congenital stop night blindness, recessive congenital stop night blindness, recessive complete congenital stop night blindness, dominant Congenital arresting night blindness, Nougarette type dominant congenital arresting night blindness, small-mouth type recessive congenital stopping night blindness, Riggs type recessive congenital stopping night blindness, Schubert-Bornschein type recessive congenital stopping night blindness, white-punctate fundus type recessive congenital stopping night blindness Retinal night blindness, complete recessive congenital stasis, X-linked congenital stasis, incomplete X-linked congenital stasis, retinal vascular disease, cerebral leukodystrophy, retinal vascular disease with cerebral leukodystrophy, recessive retinal vascular disease with cerebral leukodystrophy, dominant retinal vascular disease with cerebral leukodystrophy, Eicardi-Gutierre syndrome, Eicardi-Gutierre syndrome 1, recessive Eicardi-Gutierre syndrome 1, dominant Aicardi-Uthier syndrome 1, lupus frostbite, recessive lupus frostbite, dominant lupus frostbite, Martinique retinal dystrophy and retinitis pigmentosa, recessive Martinique retinal dystrophy and retinitis pigmentosa, dominant Martinique retinal dystrophy and retinitis pigmentosa, spinocerebellar ataxia, recessive spinocerebellar ataxia, dominant spinocerebellar ataxia, spinocerebellar ataxia with macular dystrophy, spinocerebellar ataxia with retinal degeneration,Spinocerebellar ataxia with macular dystrophy or retinal degeneration, recessive spinocerebellar ataxia with macular dystrophy or retinal degeneration, dominant spinocerebellar ataxia with macular dystrophy or retinal degeneration, Wolfram syndrome, recessive Wolfram syndrome, dominant Wolfram syndrome, low-frequency sensorineural hearing loss, recessive low-frequency sensorineural hearing loss, dominant low-frequency sensorineural hearing loss, ophthalmo-ot syndrome, recessive ophthalmo-ot syndrome, dominant ophthalmo-ot syndrome, recessive kidney, skeletal and retinal abnormalities, recessive abetalipoproteinemia, microcephaly, recessive microcephaly, dominant microcephaly, growth disorders and recessive retinopathy. Cervical dystrophy, Vietti crystalline corneal-retinal dystrophy, recessive Vietti crystalline corneal-retinal dystrophy, dominant Vietti crystalline corneal-retinal dystrophy, Wagner's disease, erosive vitreoretinopathy, Wagner's disease and erosive vitreoretinopathy, recessive Wagner's disease and erosive vitreoretinopathy, dominant Wagner's disease and erosive vitreoretinopathy, febrile seizures, recessive febrile seizures, dominant febrile seizures, dominant / recessive febrile seizures, choroidal dystrophy, recessive choroidal dystrophy, dominant choroidal dystrophy, centrally ring-shaped choroidal dystrophy, dominant centrally ring-shaped choroidal dystrophy Recessive central symmetry chorioretinoid dystrophy, epiphyseal dysplasia, recessive epiphyseal dysplasia, dominant epiphyseal dysplasia, multiple epiphyseal dysplasia, recessive multiple epiphyseal dysplasia, dominant multiple epiphyseal dysplasia, ichthyosis, recessive ichthyosis, dominant ichthyosis, quadriplegia and delayed recessive ichthyosis, chorioretinal atrophy, bifocal chorioretinal atrophy, progressive bifocal chorioretinal atrophy, recessive progressive bifocal chorioretinal atrophy, dominant progressive bifocal chorioretinal atrophy, Refsum disease, recessive Refsum disease, dominant Refsum disease, adult-type recessive Refsum disease, infant-type recessive Refsum disease, retinal cone dystrophy, recessive retinal cone dystrophy, dominant retinal cone dystrophy strophy, retinal cone dystrophy 1, recessive retinal cone dystrophy 1, dominant retinal cone dystrophy 1, type 3 dichromacy, recessive type 3 dichromacy, dominant type 3 dichromacy, mucopolysaccharidosis, recessive mucopolysaccharidosis, dominant mucopolysaccharidosis, monochromacy Pingelap, recessive monochromacy Pingelap, dominant monochromacy Pingelap, Klippel-Feuer syndrome, recessive Klippel-Feuer syndrome, dominant Klippel-Feuer syndrome, microphthalmia, recessive microphthalmia, dominant microphthalmia, limb-girdle muscular dystrophy, recessive limb-girdle muscular dystrophy, dominant limb-girdle muscular dystrophy, short-rib thoracic dysplasia, recessive short-rib thoracic dysplasia Thoracic dysplasia, dominant short-rib thoracic dysplasia, polydactyly recessive short-rib thoracic dysplasia, retinal dystrophy recessive short-rib thoracic dysplasia, intellectual disability, trunk obesity, retinal dystrophy, and micropenis (MORM) syndrome, recessive MORM syndrome, dominant MORM syndrome, spasticity and retinal degeneration recessive intellectual disability, Cockayne syndrome, recessive Cockayne syndrome, dominant Cockayne syndrome, congenital retinal detachment, recessive non-syndromic congenital retinal detachment, dominant non-syndromic congenital retinal detachment, hemolytic anemia, nonspherocytic hemolytic anemia, recessive nonspherocytic hemolytic anemia, dominant nonspherocytic hemolytic anemia, hereditary neuropathy,Hereditary neuropathy (Lasse type), recessive hereditary neuropathy (Lasse type), dominant hereditary neuropathy (Lasse type), choroidal sclerosis, recessive choroidal sclerosis, dominant choroidal sclerosis, retinopathy, recessive retinopathy, dominant retinopathy, combined dominant and recessive retinopathy, diffuse dominant retinopathy, variable dominant retinopathy, diffuse and variable dominant retinopathy, microcephaly, recessive microcephaly, dominant microcephaly, lymphedema-dominant microcephaly, chorioretinopathy-dominant microcephaly, lymphedema- and chorioretinopathy-dominant microcephaly, chorioretinopathy, recessive chorioretinopathy, dominant chorioretinopathy, chorioretinopathy and microcephaly, recessive chorioretinopathy and micro Microcephaly, dominant chorioretinopathy and microcephaly, renal coloboma syndrome, recessive renal coloboma syndrome, dominant renal coloboma syndrome, asymptomatic hearing loss, recessive asymptomatic hearing loss, dominant asymptomatic hearing loss, gyrocephalic atrophy, recessive gyrocephalic atrophy, dominant gyrocephalic atrophy, gyrocephalic retinal choroidal atrophy, vitreoretinopathy, exudative vitreoretinopathy, familial exudative vitreoretinopathy, recessive familial exudative vitreoretinopathy, dominant familial exudative vitreoretinopathy, dominant familial exudative vitreoretinopathy and Coats disease, neovascular inflammatory vitreoretinopathy, recessive neovascular inflammatory vitreoretinopathy, dominant neovascular inflammatory vitreoretinopathy, focal atrophy, recessive Sex-limited focal atrophy, dominant focal atrophy, Meckel syndrome, recessive Meckel syndrome, dominant Meckel syndrome, vitreous-retinal choriolopathy, recessive vitreous-retinal choriolopathy, dominant vitreous-retinal choriolopathy, bestrofin syndrome, recessive bestrofin syndrome, dominant bestrofin syndrome, high bone mass trait, recessive high bone mass trait, dominant high bone mass trait, osteoporosis-pseudoglioma syndrome, recessive osteoporosis-pseudoglioma syndrome, dominant osteoporosis-pseudoglioma syndrome, microphthalmia, recessive microphthalmia, dominant microphthalmia, retinal disease syndrome, recessive retinal disease syndrome, dominant retinal disease syndrome, microphthalmia and retinal disease syndrome, recessive microphthalmia and retinal disease Symptom syndrome, dominant microphthalmia and retinal disease syndrome, true microphthalmia, recessive true microphthalmia, dominant true microphthalmia, osteogenesis imperfecta, recessive osteogenesis imperfecta, dominant osteogenesis imperfecta, developmental disorders, osteoarthritis and symptomatic disorders, caudal optic disc malformation, recessive caudal optic disc malformation, dominant caudal optic disc malformation, white punctate fundus, recessive white punctate fundus, dominant white punctate fundus, mevalonic aciduria, recessive mevalonic aciduria, dominant mevalonic aciduria, hyper-IgD syndrome, recessive hyper-IgD syndrome, dominant hyper-IgD syndrome, spastic paraplegia, recessive spastic paraplegia, dominant spastic paraplegia, neuropathy recessive spastic paraplegia, optic nerve atrophy recessive spastic paraplegia,Neuropathy and optic nerve atrophy, recessive spastic paraplegia (dementia), recessive dementia, dominant dementia, familial dominant dementia, retinoblastoma, recessive retinoblastoma, dominant retinoblastoma, germline retinoblastoma, somatic retinoblastoma, dominant germline or somatic retinoblastoma, retinoblastoma, benign retinoblastoma, pineal gland, osteosarcoma, rod monochromacy, recessive rod monochromacy, dominant rod monochromacy, monochromacy, recessive monochromacy, dominant monochromacy, rod monochromacy, rod recessive monochromacy, rod dominant monochromacy, recessive rod monochromacy or monochromacy, pattern dystrophy, recessive pattern dystrophy, dominant pattern dystrophy S cone syndrome, reinforced S cone syndrome (ESC), recessive ESC, dominant ESC, Goldmann-Fabre syndrome, recessive Goldmann-Fabre syndrome, dominant Goldmann-Fabre syndrome, Bosniadystrophy, recessive Bosniadystrophy, dominant Bosniadystrophy, white punctate retinitis, recessive white punctate retinitis, dominant white punctate retinitis, mucolipidosis IIIγ, recessive mucolipidosis IIIγ, dominant mucolipidosis IIIγ, Mainzer-Sardino syndrome, recessive Mainzer-Sardino syndrome, dominant Mainzer-Sardino syndrome, elastic Fibromic pseudoxanthoma, recessive pseudoxanthoma elastica, dominant pseudoxanthoma elastica, Knobloch syndrome, recessive Knobloch syndrome, dominant Knobloch syndrome, foveal hypoplasia, recessive foveal hypoplasia, dominant foveal hypoplasia, anterior segment malformation, recessive anterior segment malformation, dominant anterior segment malformation, foveal hypoplasia and anterior segment malformation, recessive foveal hypoplasia and anterior segment malformation, dominant foveal hypoplasia and anterior segment malformation, spastic ataxia, recessive spastic ataxia, dominant spastic ataxia, de Grouchy syndrome, Boucher-Neuhauser syndrome, recessive Boucher-Neuhauser syndrome, dominant Boucher-Neuhauser Ihauser syndrome, Boucher-Neuhauser syndrome with chorioretinal dystrophy, recessive Boucher-Neuhauser syndrome with chorioretinal dystrophy, dominant Boucher-Neuhauser syndrome with chorioretinal dystrophy, hypoprebetalipoproteinemia, acanthocyanosis, retinitis pigmentosa, and globus pallidus (HARP) degeneration, recessive HARP degeneration, dominant HARP degeneration, Haller-Folden-Spatz syndrome, recessive Haller-Folden-Spatz syndrome, dominant Haller-Folden-Spatz syndrome, Alagille syndrome, recessive Alagille syndrome, dominant Alagille syndrome,Polyneuropathy, deafness, ataxia, retinitis pigmentosa and early-onset cataract (PHARC), recessive PHARC, dominant PHARC, recessive symptomatic PHARC, Sausby's retinal degeneration, recessive Sausby's retinal degeneration, dominant Sausby's retinal degeneration, vitreoretinal dystrophy, recessive vitreoretinal dystrophy, dominant vitreoretinal dystrophy, optic neuropathy, recessive optic neuropathy, dominant optic neuropathy, late-onset dominant optic neuropathy, mouth-face-finger syndrome1, Simpson-Goravi-Boehmel syndrome2, X-linked retinoschisis, X-linked Oregon eye disease, X-linked optic atrophy, retinal dysplasia, recessive retinoschisis Membrane dysplasia, dominant retinal dysplasia, X-linked retinal dysplasia, primary X-linked retinal dysplasia, X-linked Norie disease, Coats disease, X-linked Åland Island eye disease, autoimmune inner ear disease (AIED), AIED-like disease, colloideremia, X-linked colloideremia, neuropathy, optic nerve atrophy, hearing loss and retinitis pigmentosa, X-linked neuropathy, optic nerve atrophy, hearing loss and retinitis pigmentosa, X-linked blue cone monochromacy, X-linked type 1 trichromacy and rare macular dystrophy in blue cone monochromacy (BCM), X-linked type 2 trichromacy and rare macular dystrophy Trophy, mitochondrial Kearns-Sayer syndrome including retinitis pigmentosa, Leigh syndrome, retinopathy, mitochondrial pigmentary retinopathy and sensorineural hearing loss, albinism, oculocutaneous albinism, neuronal ceroid lipofuscinosis, Zellweger spectrum disorder, cobalamin C deficiency, blue cone monochromacy, hereditary red-green color blindness, type 3 color blindness and yellow-blue abnormalities, strepoptic vision, delayed cone adaptation, uveitis, diabetic retinopathy, diabetic macular edema, persistent corneal epithelial defect, neurotrophic keratitis, herpes interstitial keratitis, chronic dry eye, glaucoma, ocular detachment, ocular blister formation, ocular scarring, visual impairment, loss of vision. Brightness, corneal blindness, dry eye disease, tear-deficient dry eye disease, Sjögren's syndrome-related tear-deficient dry eye disease, non-Sjögren's syndrome-related dry eye disease, evaporative dry eye disease, meibomian gland dysfunction, blepharitis, blepharitis, ocular rosacea and atopic dermatitis, tear-deficient and evaporative dry eye diseases, Fuchs dystrophy, Fuchs corneal endothelial dystrophy (FECD), Fuchs endothelial dystrophy (FED), panuveitis, diffuse uveitis, panuveitis, cataract, partial cataract, complete cataract, sedentary cataract, progressive cataract, hard cataract,Soft cataracts, nuclear cataracts, nuclear sclerotic cataracts, cortical cataracts, posterior subcapsular cataracts, congenital cataracts, corneal dystrophy, epithelial and subepithelial dystrophy, epithelial basement membrane dystrophy, epithelial recurrent erosive dystrophy (Franschetty corneal dystrophy, Dystrophia smolandiensis, and / or Dystrophia helsinglandica), subepithelial mucinous corneal dystrophy, Miesmann corneal dystrophy, Risch epithelial corneal dystrophy, gelatinous drop-like corneal dystrophy, Bowman's layer dystrophy Trophy, Reis-Bücklers corneal dystrophy, Thiel-Benkhe corneal dystrophy, stromal dystrophy-TGFB1 corneal dystrophy, lattice corneal dystrophy, type 1 variant of lattice corneal dystrophy (III, IIIA, I / IIIA, IV), granular corneal dystrophy type 1, granular corneal dystrophy type 2, stromal dystrophy, maculoplasty, Schneider crystalline corneal dystrophy, congenital stromal corneal dystrophy, Fleck's dystrophy, posterior chemoathion Rufus corneal dystrophy, François central cloud dystrophy, pre-Descemet's corneal dystrophy, endothelial dystrophy, Fuchs dystrophy, posterior polymorphic corneal dystrophy, congenital hereditary endothelial dystrophy, X-linked corneal endothelial dystrophy, superficial dystrophy, epithelial basement membrane dystrophy, Miesmann juvenile corneal epithelial dystrophy, gelatinous drop-like corneal dystrophy, Risch epithelial corneal dystrophy, subepithelial mucinous corneal dystrophy, Reiss-Bücklers corneal dystrophy, The method according to claim 72 or claim 73, selected from the group consisting of Thiel-Benkez dystrophy, stromal dystrophy, lattice corneal dystrophy, granular corneal dystrophy, maculoplasty, Schneider crystalline corneal dystrophy, congenital stromal corneal dystrophy, Fleck's dystrophy, posterior dystrophy, Fuchs dystrophy, posterior polymorphic corneal dystrophy, congenital hereditary endothelial dystrophy, keratopathy, corneal keratopathy, and calcific corneal keratopathy.

75. The method according to any one of claims 72 to 74, wherein the eye condition or disease is neurotrophic keratitis, Stargardt disease, or Leber's congenital amaurosis.

76. The method according to any one of claims 72 to 75, wherein the eye condition or disease is neurotrophic keratitis.

77. The method according to any one of claims 72 to 75, wherein the eye condition or disease is Stargardt disease.

78. The method according to any one of claims 72 to 75, wherein the eye condition or disease is Leber's congenital amaurosis.

79. The method according to any one of claims 70 to 74, wherein the subject is a human.

80. The method according to any one of claims 70 to 79, wherein the herpes virus or pharmaceutical composition is administered to the subject by injection, by injection into the eye, by subretinal injection, by intraocular injection, by intravitreous injection, by suprachoroidal injection, by intrachorionic injection, intraocular, intravitreous, locally, subcutaneously, subconjunctivally, subtenon, intrachorionic, posteriorly, systemically, parenterally, periophthalmos, near the sclera, near the anterior sclera, near the posterior sclera, orally, periophthalmos, or onto the choroid.

81. The method according to any one of claims 70 to 80, wherein the herpes virus or pharmaceutical composition is administered to the subject by injection into the eye, by subretinal injection, by intravitreal injection, onto the choroid, or locally.

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