Methods and compositions for treating conditions involving eye

Abstract

The present disclosure provides a recombinant nucleic acid comprising one or more polynucleotides encoding a polypeptide; a virus comprising the recombinant nucleic acid; compositions and formulations comprising the recombinant nucleic acid and / or the virus; methods of their use (e.g., for treating one or more ocular conditions or diseases); and articles or kits thereof.

Description

Cross-reference to related applications

[0001] This application claims priority to U.S. Provisional Application Serial No. 63 / 459,102, filed April 13, 2023; U.S. Provisional Application Serial No. 63 / 460,948, filed April 21, 2023; and U.S. Provisional Application Serial No. 63 / 593,085, filed October 25, 2023, the contents of which are incorporated herein by reference in their entirety. Sequence List Information

[0002] The sequence list relating to this application was submitted electronically through the Patent Center and is hereby incorporated in its entirety by reference. The file containing the sequence list is named 2401989.xml. The file size is 1,738,822 bytes, and the file was created on April 12, 2024. Technical Field

[0003] This disclosure relates in part to recombinant nucleic acids comprising one or more polynucleotides encoding polypeptides, viruses comprising said recombinant nucleic acids, pharmaceutical compositions and formulations thereof, and methods of using them (e.g., for treating one or more eye conditions or diseases). Background Technology

[0004] Eye conditions, vision loss, eye diseases, and / or visual impairments impose a significant economic burden, estimated at approximately $139 billion annually in the United States. Despite substantial advances in clinical care and treatment, more effective treatment options remain needed.

[0005] All references cited in this article (including patent applications, patent publications, non-patent documents, and NCBI / UniProtKB / Swiss-Prot accession numbers) are incorporated into this article as a whole, as if each individual reference were explicitly and separately indicated to be incorporated by reference. Summary of the Invention

[0006] To meet these and other needs, this document provides recombinant nucleic acids encoding one or more polypeptides (e.g., recombinant herpesvirus genomes), viruses containing said recombinant nucleic acids (e.g., recombinant herpesvirus genomes) (e.g., herpesviruses), pharmaceutical compositions and preparations, pharmaceutical agents, and / or methods of administration to subjects in need (e.g., for the treatment of eye conditions or diseases).

[0007] Therefore, certain aspects of this disclosure relate to a recombinant herpesvirus genome 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 replicable. In some embodiments, the recombinant herpesvirus genome is replication-deficient. In some embodiments that can be combined with any of the foregoing embodiments, the recombinant herpesvirus genome comprises the one or more polynucleotides encoding the polypeptides within one or more viral loci. In some embodiments that can be combined with any of the foregoing 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 foregoing 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 can be combined with any of the foregoing embodiments, the recombinant herpes simplex virus genome has been 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 can be combined with any of the foregoing embodiments, the recombinant herpes simplex virus genome contains inactivating mutations. In some embodiments, the inactivating mutation is located in a 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 Infected Cell Protein (ICP) 0 (one or two copies), ICP4 (one or two 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 foregoing embodiments, the recombinant herpes simplex virus genome contains an inactivating mutation in one or two copies of the ICP4 gene. In some embodiments that can be combined with any of the foregoing 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 foregoing 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 foregoing 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 foregoing 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 foregoing 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 foregoing 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 include an inactivating mutation in one or both copies of the ICP34.5 gene. In some embodiments that can be combined with any of the foregoing embodiments, the recombinant herpes simplex virus genome does not include an inactivating mutation in the UL36 gene.

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

[0011] In some embodiments that can be combined with any of the foregoing embodiments, the polypeptide is a human polypeptide. In some embodiments that can be combined with any of the foregoing embodiments, the polypeptide is selected from the following: sterile alpha motif domain-containing protein 11, nephrocystin-4, espin, nicotinamide / nicotinic acid mononucleotide adenosyltransferase 1, mitochondrial fusion protein 2, endoplasmic reticulum membrane protein complex subunit 1, group V phospholipase A2, dehydrogenase-1,2-N-acetylglucosamine aminotransferase subunit, palmitoyl protein thioesterase 1, elongation of very long chain fatty acids protein 1, protein O-linked mannose β-1,2-N-acetylglucosamine aminotransferase 1, retinoid isomerase, retinal-specific phospholipid transport ATPase, collagen α-1(XI), guanine nucleotide-binding protein G(t) subunit α-2, chloride channel CLIC-like protein 1, and DNA damage-regulated autophagy modulator protein 2. 2) U4 / U6 small nucleoribonucleoprotein Prp3, α-sulfonamide, semaphorin-4A, cyclic AMP-dependent transcription factor ATF-6α, hemicentin-1, complement factor H, crumbs protein homolog 1, adiponectin receptor protein 1, RD3 protein, serine / threonine protein kinase Nek2, feline leukemia virus C subset receptor-associated protein 1, Usherin, serologically defined colon cancer antigen 8, olfactory receptor 2W3, NBAS subunit of NRZ tethering complex, cytoplasmic carboxypeptidase-like protein 5, zinc finger protein 513, flagellated intratransporter protein 172 homolog, photoreceptor cilium actin regulator. regulator), EGF-containing fibula protein-like extracellular matrix protein 1 / TLE family member 5, FAM161A protein, fritz homolog containing WD repeat sequence, centrosome-associated protein ALMS1, U5 small nucleonucleotide 200kDa helicase, metallotransferase CNNM4, cyclic nucleotide-gated cation channel α-3, renal cystin 1, tyrosine protein kinase Mer, Bardet-Biedl syndrome 5 protein, ceramide kinase-like protein, neurogenic differentiation factor 1, transmembrane protein 237, inward rectifier potassium channel 13, S-arrestin, secreted phosphoprotein 24, mitochondrial CCA tRNA nucleotide transferase 1, sodium bicarbonate cotransporter 3, leucine zipper transcription factor-like protein 1, guanine nucleotide-binding protein G(t) subunit α-1, 3' repair exonuclease 1, MAP kinase-activated protein kinase 3, ataxia protein 7, vitamin K-dependent protein S, ADP ribosylation factor-like protein 6, photoreceptor interstitial proteoglycan 2, IQ calmodulin-binding motif-containing protein 1 1) Rhodopsin, renal cystin 3, Clarin-1, 14 members of the possible cationic amino acid transporter / solute carrier family 7, phosphocholine cytyltransferase A, 19 kDa centrosome protein, rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit beta, Wolframin, homeobox protein HMX1, Ras-related protein Rab-28, protein 2A containing coiled-coil and C2 domain, Prominin-1, adhesion G protein-coupled receptor A3, protein 1 containing death domain, protein 19 containing WD repeat sequence, cGMP-gated cation channel α-1, protein 2 containing CDGSH iron-sulfur domain, large subunit of microsomal triglyceride transporter, protein 3 containing leucine-rich repeat, immunoglobulin-like domain and transmembrane domain. 3) Immunoglobulin-like domain and transmembrane domain-containing protein; 7) Baldr-Biedel syndrome-related protein; 12) Baldr-Biedel syndrome-related protein; 8) Protein containing major facilitating superfamily domain; PLK4 (serine / threonine protein kinase); 4) Lecithin retinyl acyltransferase; 3) Toll-like receptor; 4) Cytochrome P450.4V2, spliceosome-associated protein CWC27 homolog, centrosome protein POC5, multifunctional proteoglycan core protein, adhesion G protein-coupled receptor V1, COUP transcription factor 1, mitochondrial outer membrane protein SLC25A46, catalin α-1, cytoplasmic histidine-tRNA ligase, rod cGMP-specific 3',5'-cyclic nucleotide phosphodiesterase subunit α, metabolite glutamate receptor 6, serine / threonine protein kinase MAK, complement C2, complement factor B, Tubby-associated protein 1, guanylate cyclase activator 1, guanylate cyclase activator 2, peripheral protein 2, photoreceptor intercellular matrix proteoglycan 1, eyes Shut protein homolog, collagen α-1 (IX) chain, regulatory synaptic exocytogenin 1, Lebercilin, very long chain fatty acid elongation protein 4, PR domain zinc finger protein 13, mitochondrial reticulin 4 interacting protein 1, Jouberin, peroxisome guide signal 2 receptor, CCR4-NOT transcription complex subunit 9, aryl hydrocarbon receptor, Kelch-like protein 7, retinitis pigmentosa type 9 protein, PTHB1 protein, peroxisome ATPase PEX1, tetratransmembrane protein 12, inosine-5'-monophosphate dehydrogenase 1, short-wavelength sensitive opsin 1, UPF0606 protein KIAA1549, retinitis pigmentosa type 1 protein-like 1 protein, protein containing detegrin metalloproteinase domain 9, heparin-α-glucosinolate N-acetyltransferase, oxygen regulator protein 1, α-tocopherol transporter, centrosome and spindle polar-associated protein 1, mitochondrial activator protein-like 120 kDa protein, peroxisome biogenesis factor 2, cyclic nucleotide-gated cation channel β-3, cilia and flagella-associated protein 418, growth differentiation factor 6, regulatory synaptic exocytogenin 2, voltage-gated potassium channel subfamily V member 2, E3 ubiquitin-protein ligases Topors, 78 kDa centrosome protein, Inversin, U4 / U6 small nucleoribonucleoprotein Prp4, Whirlin, E3 ubiquitin-protein ligase TRIM32, Toll-like receptor 4, cytoplasmic dysmin 2 intermediate chain 2, programmed cell death protein 2, exosome complex component RRP4, type IV phosphatidylinositol polyphosphate 5-phosphatase, peroxisome phytyl-CoA dioxygenase, acyl-CoA-binding domain 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, kinin-like protein KIF11, retinol-binding protein 4, cone cGMP-specific 3',5'-cyclic nucleotide phosphodiesterase subunit α (Cone cGMP-specific3',5'-cyclic phosphodiesterase subunit alpha), Pax-2 (pairing box protein), PDZ domain-containing protein 7, ADP-ribosylation factor-like protein 3, BBSome interacting protein 1, age-related macular degeneration susceptibility protein 2, serine protease HTRA1, mitochondrial ornithine aminotransferase, zinc finger protein 408, Tubby protein homolog, transcription enhancer TEF-1, Harmonin, transmembrane protein 216, Bestrophin-1, isaspartate peptidase / L-asparaginase, rod outer membrane protein 1, Baldr-Biedel syndrome-associated protein 1, calcium-binding protein 4, low-density lipoprotein receptor-associated protein 5, calpain 5, unconventional myosin VIIa, transmembrane protein 126A, coilin 4, cytoplasmic dysin 2 light intermediate chain 1, 164 kDa centrosomal protein, complement C1q tumor necrosis factor-related protein 5, membrane coil-related protein, voltage-dependent calcium channel subunits 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 gamma, collagen α-1(II) chain, matrix metalloproteinase 19, retinol dehydrogenase 5, T complex protein 1 subunit β, Baldr-Biedel syndrome-related protein 10, 290 kDa centrosomal protein, POC1 centriolein homolog B, mevalonate kinase, flagellated transporter 81 homolog, rescue mitochondrial translation release factor (rescue), integrated membrane protein 2B, retinoblastoma-associated protein, protein 1 containing RCC1 and BTB domains, rhodopsin kinase 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, microtubule polyglutamylase TTLL5 (Tubulin polyglutamylase)TTLL5), spermatogenesis-related protein 7, triangular tetrapeptide repeat protein 8, peroneal protein 5, transient receptor potential cation channel subfamily M member 1, γ-tubulin complex component 4, sodium / potassium / calcium exchanger 1, photoreceptor-specific nuclear receptor, Baldr-Biedel syndrome-related protein 4, calcium and integrin binding family member 2, retinaldehyde binding protein 1, N-acetylglucosamine-1-phosphotransferase subunit γ, flagellar transporter 140 homolog, clustering-related protein 1, ATP-binding box subfamily C member 6, ketoimine reductase μ-crystal protein, battenin, zinc finger protein 423, fantom protein, Baldr-Biedel syndrome-related protein 2, ADP-ribosylation factor-like protein 2 binding protein, cyclic nucleotide-gated cation channel β-1, cadherin 3, pre-mRNA splicing factor ATP-dependent RNA helicase PRP 16, disintegrin and metalloproteinase 18 containing platelet-reactive protein motif Withthrombospondin motifs 18), solute carrier family 38 members 8, retinal guanylate cyclase 1, pre-mRNA processing splicing factor 8, aryl-hydrocarbon-interacting protein-like 1, membrane-associated phosphatidylinositol transporter 3, unc-119 protein homolog A, possible G protein-coupled receptor 179, Tectonic-like complex member MKS1, carbonic anhydrase 4, G protein signaling regulator 9, arylsulfatase G, pre-mRNA splicing regulator USH1G, photoreceptor disk component PRCD, myofascitis 2, rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit γ gamma), laminin subunit α-1, AFG3-like protein 2, cone-rod homeobox protein, receptor expression enhancer protein 6, retinal and anterior nerve fold homeobox protein 2, complement C3, Rho guanine nucleotide exchange factor 18, and pattin-like phospholipase domain-containing protein 6.6) G protein signaling regulator 9 binding protein, optic dystrophin 3, U4 / U6 small nucleoribonucleoprotein Prp31, mitochondrial isocitrate dehydrogenase [NAD] subunit β, mitochondrial pantothenic acid kinase 2, jagged-1 protein, molecular chaperone MKKS, centrosome protein kizuna, lysophosphatidylserine lipase ABHD12, kinin-like protein KIF3B, centrosome-associated protein CEP250, pre-mRNA processing factor 6, ciliary and flagella-associated protein 410, activator 1-like protein, metalloproteinase inhibitor 3, flagellar intratransporter 27 homolog, peroneal protein 1, MIEF1 upstream open reading frame protein, mitochondrial aconitine hydratase, γ-tubulin complex component 6, centrioles and centriolear satellite proteins, retinal schisin, XRP2 protein, dystrophin, X-linked retinitis pigmentosa GTPase regulator, night blindness protein, Xaa-Pro Dipeptidase, Norrin, voltage-dependent L-type calcium channel subunit α-1F, phosphoglycerate kinase 1, Rab protein geraniol-geraniol transferase component A1, mitochondrial ingress membrane translocase subunit Tim8A, phosphoribosylpyrophosphate kinase 1, long-wavelength opsin 1, medium-wavelength opsin 1, short-wavelength opsin 1, mitochondrial transcription factor A, 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, mitochondrial leucine-tRNA ligase, mitochondrial nondiscriminating glutamyl-tRNA synthetase EARS2 (Nondiscriminating) Glutamic acid-tRNA synthetase EARS2 (mitochondrial), lysine-tRNA ligase, mitochondrial histidine-tRNA ligase, mitochondrial serine-tRNA ligase, mitochondrial proline-tRNA ligase, cyanocobalamin reductase / alkylcobamamin dealkylase, POU domain, class 3 transcription factor 4, ribosomal protein S6 kinase α-6, ciliogenesis and planar polarity effector 1, Meckelin, TRAF3 interacting protein 1, flagellated transporter 74 homolog, S-phase cyclin A-associated protein in the endoplasmic reticulum.Proteins in the endoplasmic reticulum, sodium channel and clathrin linker 1, TALPID3 protein, Tectonic-2, ADP-ribosylation factor-like protein 13B, protein 1 containing B9 domain, protein 2 containing B9 domain, protein 3 containing C2 domain, 41 kDa centrosomal protein, 104 kDa centrosomal protein, 120 kDa centrosomal protein, flagellated transporter 172 homolog, chevone interacting protein, kinin-like protein KIF7, rod rhodopsin-sensitive cGMP 3',5'-cyclic nucleotide phosphodiesterase subunit δ, Tectonic-1, Tectonic-3, transmembrane protein 107, transmembrane protein 138, transmembrane protein 231, triangular tetrapeptide 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 binding homeobox protein 1, type II cuticular Hb3, type I cytoskeleton 12, transforming growth factor β-inducible protein ig-h3, tumor-associated calcium signaling protein 2, carbohydrate sulfonyltransferase 6, coagulin, protein containing UbiA isopentenyltransferase domain 1, core proteoglycan, 1-phosphatidylinositol 3-phosphate 5-kinase, transcription factor Ovo-like 2 protein 2) and Grainyhead-like protein 2 homolog.

[0012] In some embodiments that can be combined with any of the foregoing embodiments, the recombinant herpesvirus genome exhibits reduced cytotoxicity when introduced into target cells compared to the corresponding wild-type herpesvirus genome. In some embodiments, the target cells are human cells. In some embodiments, the target cells are cells of the eye. 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 a herpesvirus comprising any recombinant herpesvirus genome described herein. In some embodiments, the herpesvirus is replicative. In some embodiments, the herpesvirus is replication-defective. In some embodiments that can be combined with any of the foregoing embodiments, the herpesvirus is not oncolytic. In some embodiments that can be combined with any of the foregoing embodiments, the herpesvirus is a pseudotyped virus. In some embodiments that can be combined with any of the foregoing embodiments, the herpesvirus is not a pseudotyped virus. In some embodiments that can be combined with any of the foregoing embodiments, the herpesvirus is not a pseudotyped oncolytic virus. In some embodiments that can be combined with any of the foregoing embodiments, the herpesvirus has reduced cytotoxicity compared to the corresponding wild-type herpesvirus. In some embodiments that can be combined with any of the foregoing 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 foregoing 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, the HSV-1 is not oncolytic.

[0014] Other aspects of this disclosure relate to a pharmaceutical composition comprising any recombinant herpesvirus genome and / or any recombinant herpesvirus described herein, along with a pharmaceutically acceptable vector or excipient. In some embodiments that can be combined with any of the foregoing embodiments, the pharmaceutical composition is suitable for ocular, subretinal, intraocular, intravitreal, topical, subcutaneous, subconjunctival, subtenon, subtenoncapsule, anterior chamber, retrobulbar, systemic, parenteral, periocular, scleral, anterior scleral, posterior scleral, oral, periocular, or choroidal administration. In some embodiments that can be combined with any of the foregoing embodiments, the pharmaceutical composition comprises phosphate-buffered saline. In some embodiments that can be combined with any of the foregoing embodiments, the pharmaceutical composition comprises glycerol. In some embodiments that can be combined with any of the foregoing embodiments, the pharmaceutical composition comprises a lipid carrier. In some embodiments that can be combined with any of the foregoing 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 genome), recombinant viruses (e.g., recombinant herpesvirus), and / or pharmaceutical compositions described herein as pharmaceutical agents.

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

[0017] Other aspects of this disclosure relate to the use of any of the recombinant nucleic acids (e.g., recombinant herpesvirus genome), recombinant viruses (e.g., recombinant herpesvirus), and / or pharmaceutical compositions described herein in the preparation of a medicament for treating an eye condition or disease.

[0018] Other aspects of this disclosure relate to a method of expressing, enhancing, increasing, enlarging, and / or supplementing the levels of a polypeptide in one or more cells of a subject, said method comprising administering to the subject an effective amount of any of the recombinant herpesvirus and / or pharmaceutical compositions described herein. In some embodiments, said one or more cells are one or more cells of the eye. In some embodiments that may be combined with any of the foregoing embodiments, said subject is a human. In some embodiments that may be combined with any of the foregoing embodiments, said herpesvirus or said pharmaceutical composition is administered via injection, via injection into the eye, via subretinal injection, via intraocular injection, via intravitreal injection, via suprachoroidal injection, intraocularly, intravitreally, externally, subcutaneously, subconjunctivally, subfascially, intraanteriorly, retrobulbarly, systemically, parenterally, periocularly, near the sclera, anterior near the sclera, posterior near the sclera, orally, peribulbarly, or suprachoroidally.

[0019] Other aspects of this disclosure relate to a method of providing prophylactic, palliative, or therapeutic relief of one or more signs or symptoms of an eye condition or disease in a subject in need, the method comprising administering to the subject an effective amount of any of the recombinant herpesvirus and / or pharmaceutical compositions described herein. In some embodiments, the eye condition or disease is selected from retinitis pigmentosa, latent retinitis pigmentosa, severe latent retinitis pigmentosa, overt retinitis pigmentosa, overt retinitis pigmentosa with choroidal involvement, latent retinitis pigmentosa with para-arteriolar preservation of the RPE (PPRPE), latent retinitis pigmentosa with posterior column ataxia (PCARP), and latent retinitis pigmentosa with erythrocytic... Microcytosis, Syndrome of latent retinitis pigmentosa, Latent syndrome with retinitis pigmentosa, Non-syndrome of latent retinitis pigmentosa, Non-syndrome of overt retinitis pigmentosa, Syndrome of overt retinitis pigmentosa, Juvenile latent retinitis pigmentosa, Latent retinitis pigmentosa with intellectual disability, Latent retinitis pigmentosa with macular degeneration, Severe early-onset latent retinitis pigmentosa, Latent retinitis pigmentosa with skeletal abnormalities, Latent retinitis pigmentosa with skeletal deformities, Overt retinitis pigmentosa with sensorineural ear disease. Deafness, latent retinitis pigmentosa with hearing loss, latent retinitis pigmentosa with hearing loss and other impairments, latent retinitis pigmentosa with vitreous changes, early-onset latent retinitis pigmentosa with macular defects, X-linked retinitis pigmentosa, latent 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, Bardet-Biedl-like retinitis pigmentosa. Retinitis pigmentosa, Baldr-Beedel syndrome-like latent retinitis pigmentosa, digenic retinitis pigmentosa, digenic retinitis pigmentosa with retinal outer segment membrane protein 1 abnormality, digenic retinitis pigmentosa with PRPH2 abnormality, latent retinitis pigmentosa with early macular involvement, latent hearing loss without retinitis pigmentosa,Latent congenital deafness without retinitis pigmentosa, latent retinitis pigmentosa with latent ataxia, latent retinitis pigmentosa with 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 deafness and neurological abnormalities, autosomal dominant retinitis pigmentosa, non-syndromic autosomal dominant retinitis pigmentosa, autosomal recessive retinitis pigmentosa, non-syndromic autosomal recessive retinitis pigmentosa, retinal pigment epithelium (RPE), latent RPE, dominant RPE, latent RPE degeneration, dominant RPE degeneration, ataxia, latent ataxia, dominant ataxia, Sinier-Lukehn syndrome, latent Sinier-Lukehn syndrome, dominant Sinier-Lukehn syndrome Neill-Lukehn syndrome, renal wasting disease, latent renal wasting disease, overt renal wasting disease, juvenile latent renal wasting disease, ciliopathy-associated latent renal wasting disease, juvenile renal wasting disease, juvenile latent renal wasting disease, juvenile overt renal wasting disease, Usher syndrome, Usher syndrome type I, Usher syndrome type II, Usher syndrome type III, latent Usher syndrome, atypical latent Usher syndrome, overt Usher syndrome, type 2 latent Usher syndrome, type 2a latent Usher syndrome, type 3 latent Usher syndrome, type 3-like latent Usher syndrome, atypical latent Usher syndrome, type 1 latent Usher syndrome, type 1b latent Usher syndrome, type 1d latent Usher syndrome, type 1f latent Usher syndrome, type 1J latent Usher syndrome, type 1k latent Usher syndrome, digenic Usher syndrome due to CDH23 abnormality. Usher syndrome with CDH23, digenic Usher syndrome with PCDH15 abnormalities. PCDH15), Acadia type recessive Usher syndrome, recessive atypical Usher syndrome (USH3-like), Leber congenital amaurosis, recessive Leber congenital amaurosis, dominant Leber congenital amaurosis, new-onset Leber congenital amaurosis, dominant Leber congenital amaurosis with 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 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-methylpentanoic aciduria, dominant optic atrophy with cataracts, ataxia and areflexia, Kjer type dominant optic atrophy. Atrophy, overt optic atrophy with sensorineural hearing loss, latent cerebellar degeneration with optic atrophy, and optic atrophy with deafness-dystonia syndrome.X-linked optic atrophy with deafness-dystonia syndrome, retinal dystrophy, latent retinal dystrophy, overt retinal dystrophy, hereditary retinal dystrophy, early-onset latent retinal dystrophy, latent syndromic retinal dystrophy, latent non-syndromic retinal dystrophy, latent syndromic and non-syndromic retinal dystrophy, latent optic atrophy with retinal dystrophy, latent retinal dystrophy with obesity, latent retinal dystrophy with cerebellar dysplasia, syndromic latent optic atrophy with retinal dystrophy, overt retinal dystrophy with iris defects, and the spectrum of ciliopathies including retinal dystrophy. dystrophy), including latent ciliary spectrum disorders of retinal dystrophy, overt ciliary spectrum disorders of retinal dystrophy, overt optic atrophy with neuropathy and myopathy, overt optic atrophy with intellectual disability and developmental delay, syndromic optic atrophy, nonsyndromic optic atrophy, latent nonsyndromic optic atrophy, overt nonsyndromic optic atrophy, latent syndromic optic atrophy, overt syndromic optic atrophy, Charcot-Marie-Tuss disease, latent Charcot-Marie-Tuss disease, overt Charcot-Marie-Tuss disease, benign fleck retina. Retina), latent benign maculatic retina, overt benign maculatic retina, syndromic retinopathy, latent syndromic retinopathy, overt syndromic retinopathy, Barten disease, latent Barten disease, overt Barten disease, latent Barten disease (neuronal ceroid lipofuscinosis type 3), juvenile latent Barten disease (neuronal ceroid lipofuscinosis type 3), neuronal ceroid lipofuscinosis, latent neuronal ceroid lipofuscinosis, latent neuronal ceroid lipofuscinosis type 1, overt neuronal ceroid lipofuscinosis, Stargardt disease, latent Stargardt disease, overt Stargardt disease, juvenile Stargardt disease, late-onset Stargardt disease, Stargardt-like macular dystrophy dystrophy), latent Statart's disease-like macular dystrophy, dominant Statart's disease-like macular dystrophy, macular dystrophy, latent macular dystrophy, early-onset macular dystrophy, adult-onset macular dystrophy, early-onset latent macular dystrophy, adult-onset latent macular dystrophy, early-onset adult-onset latent macular dystrophy, juvenile latent macular dystrophy with sparse hairs, dominant macular dystrophy, late-onset dominant macular dystrophy, dominant macular dystrophy with lens zonules, bull's-eye dominant macular dystrophy.Butterfly-shaped dominant macular dystrophy, age-related dominant macular dystrophy, benign concentric ring dominant macular dystrophy, yolk-like recessive macular dystrophy, yolk-like dominant macular dystrophy, atypical yolk-like dominant macular dystrophy, dominant adult-type yolk-like macular dystrophy, Stagger's disease-like dominant macular dystrophy, Stagger's disease-type dominant macular dystrophy, North Carolina-type dominant macular dystrophy, North Carolina-type-like dominant macular dystrophy, North Carolina-type-like with progressive sensory nerve damage. Dominant macular dystrophy, cystoid dominant macular dystrophy, Best type dominant macular dystrophy, occult macular dystrophy, latent occult macular dystrophy, dominant occult macular dystrophy, age-related familial macular dystrophy, X-linked atrophic macular dystrophy, latent X-linked atrophic macular dystrophy, dominant X-linked atrophic macular dystrophy, mitochondrial macular pattern dystrophy with type II diabetes and hearing loss (deafness), yellow macular deafness, latent yellow macular deafness, manifest yellow macular deafness, rod dystrophy, latent rod dystrophy, manifest rod dystrophy, cone dystrophy, latent cone dystrophy, manifest cone dystrophy, latent cone dystrophy with rod electroretinogram abnormalities, early-onset latent cone dystrophy, late-onset latent cone dystrophy, cone dystrophy type 1, X-linked cone dystrophy type 1, cone dystrophy type 2, progressive cone dystrophy type 2, X-linked progressive cone dystrophy type 2, delayed cone adaptation, latent cone adaptation, delayed manifest cone adaptation, cone-rod dystrophy, latent cone-rod dystrophy, manifest cone-rod dystrophy, isolated cone-rod dystrophy, progressive cone-rod dystrophy, X-linked cone-rod dystrophy, X-linked progressive cone-rod dystrophy Rod dystrophy, progressive dominant cone-rod dystrophy, cone-rod dystrophy with enamel hypoplasia syndrome, latent cone-rod dystrophy with enamel hypoplasia syndrome, dominant cone-rod dystrophy with enamel hypoplasia syndrome, latent cone-rod dystrophy with inner retinal lesions, latent cone-rod dystrophy with skeletal diseases, congenital syndromic non-progressive latent cone-rod dystrophy, latent cone-rod dystrophy with hearing loss, latent cone-rod dystrophy with psychomotor delay, latent cone with cone-rod dystrophy, cone-rod synaptic diseases, congenital cone-rod synaptic diseases, latent congenital cone-rod synaptic diseases, dominant congenital cone-rod synaptic diseases, rod-cone dystrophy, latent cone-rod dystrophy, dominant cone-rod dystrophy, early-onset latent cone-rod dystrophy.Non-syndromic latent rod-cone dystrophy, latent Newfoundland type rod-cone dystrophy, latent progressive cone dystrophy, Stickler syndrome, dominant Stickler syndrome, latent Stickler syndrome, dominant Stickler syndrome type I, dominant Stickler syndrome type II, Marshall syndrome, dominant Marshall syndrome, latent Marshall syndrome, achromatopsia, latent achromatopsia, dominant achromatopsia, latent complete achromatopsia, latent incomplete achromatopsia, 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. Age-related macular degeneration, drusen, latent drusen, dominant drusen, early-onset latent drusen, early-onset dominant drusen, macular drusen, dominant radial macular drusen, pigmented paravenous choroidal retinal atrophy, latent pigmented paravenous choroidal retinal atrophy, dominant pigmented paravenous choroidal retinal atrophy, progressive bifocal choroidal retinal atrophy, Balder-Biedel syndrome, latent Balder-Biedel syndrome, dominant Balder-Biedel syndrome, latent Balder-Biedel syndrome with developmental abnormalities, retinal degeneration, latent retinal degeneration, dominant retinal degeneration, non-syndromic latent retinal degeneration, multifactorial celluloid retinal degeneration (Doyne Honeycomb retinal degeneration, latent multifactorial honeycomb retinal degeneration, overt multifactorial honeycomb retinal degeneration (Malattia Leventinese), latent renal wasting disease with retinal degeneration, Alstrom syndrome, latent Alstrom syndrome, overt Alstrom syndrome, Joubert syndrome Syndrome, including latent Jobert syndrome, dominant Jobert syndrome, Jobert syndrome, latent Jobert syndrome, dominant Jobert syndrome, X-linked Jobert syndrome, vitreoretinal degeneration, latent vitreoretinal degeneration, dominant vitreoretinal degeneration, snowflake vitreoretinal degeneration, snowflake dominant vitreoretinal degeneration, microstomia, latent microstomia, dominant microstomia, night blindness, stationary night blindness, congenital night blindness, congenital stationary night blindness, severe congenital stationary night blindness, latent congenital stationary night blindness, latent complete congenital stationary night blindness, dominant congenital stationary night blindness, Nougaret type dominant congenital stationary night blindness, and Oguchi type recessive congenital stationary night blindness.Riggs type recessive congenital stationary night blindness, Schubert-Bornschein type recessive congenital stationary night blindness, punctate fundus type recessive congenital stationary night blindness, complete recessive congenital stationary night blindness, X-linked congenital stationary night blindness, incomplete X-linked congenital stationary night blindness, retinal vascular disease, leukodystrophy, retinal vascular disease with leukodystrophy, latent retinal vascular disease with leukodystrophy, overt retinal vascular disease with leukodystrophy, Aicardi-Goutiere syndrome. Ecardi-Gutier syndrome type 1, latent Ecardi-Gutier syndrome type 1, dominant Ecardi-Gutier syndrome type 1, frostbite-like lupus, latent frostbite-like lupus, dominant frostbite-like lupus, Martinic retinal dystrophy with retinitis pigmentosa, latent Martinic retinal dystrophy with retinitis pigmentosa, dominant Martinic retinal dystrophy with retinitis pigmentosa, spinocerebellar ataxia, latent spinocerebellar ataxia, dominant spinocerebellar ataxia, spinocerebellar ataxia with macular dystrophy, spinocerebellar ataxia with retinal degeneration, spinocerebellar ataxia with macular dystrophy or retinal degeneration. Latent spinocerebellar ataxia with macular dystrophy or retinal degeneration, overt spinocerebellar ataxia with macular dystrophy or retinal degeneration, Wolverhampton syndrome, latent Wolverhampton syndrome, overt Wolverhampton syndrome, low-frequency sensorineural hearing loss, latent low-frequency sensorineural hearing loss, overt low-frequency sensorineural hearing loss, oculo-otonic syndrome, latent oculo-otonic syndrome, overt oculo-otonic syndrome, latent kidney, skeletal and retinal abnormalities, latent abeloinemia, microcephaly, latent microcephaly, overt microcephaly, latent microcephaly with growth retinal disease, Bietti crystalline kerato-retinal dystrophy. (corneoretinal dystrophy), latent pedicled crystalline keratoretinal dystrophy, overt pedicled crystalline keratoretinal dystrophy, Wagner's disease, erosive vitreoretinopathy, Wagner's disease with erosive vitreoretinopathy, latent Wagner's disease with erosive vitreoretinopathy, overt Wagner's disease with erosive vitreoretinopathy, febrile seizures, latent febrile seizures, overt febrile seizures, overt / latent febrile seizures, choroidal dystrophy, latent choroidal dystrophy, overt choroidal dystrophy,Central halo choroidal dystrophy, dominant central halo choroidal dystrophy, latent central halo choroidal dystrophy, epiphyseal dysplasia, latent epiphyseal dysplasia, dominant epiphyseal dysplasia, multiple epiphyseal dysplasia, latent multiple epiphyseal dysplasia, dominant multiple epiphyseal dysplasia, ichthyosis, latent ichthyosis, dominant ichthyosis, latent ichthyosis with quadriplegia and flaccidity, choroidal-retinal atrophy, bifocal choroidal-retinal atrophy, progressive bifocal choroidal-retinal atrophy, latent progressive bifocal choroidal-retinal atrophy, dominant progressive bifocal choroidal atrophy. Choroidal retinal atrophy, Rifsum's disease, latent Rifsum's disease, dominant Rifsum's disease, adult-onset latent Rifsum's disease, infantile latent Rifsum's disease, retinal-cone dystrophy, latent retinal-cone dystrophy, dominant retinal-cone dystrophy, retinal-cone dystrophy type 1, latent retinal-cone dystrophy type 1, dominant retinal-cone dystrophy type 1, blue-yellow color blindness, latent blue-yellow color blindness, dominant blue-yellow color blindness, mucopolysaccharidosis, latent mucopolysaccharidosis, dominant mucopolysaccharidosis, Pingerapu achromatopsia Pingelapese, latent Pingelapese achromatopsia, dominant Pingelapese achromatopsia, Krippel-Fair syndrome, latent Krippel-Fair syndrome, dominant Krippel-Fair syndrome, microphthalmia, latent microphthalmia, dominant microphthalmia, limb-girdle muscular dystrophy, latent limb-girdle muscular dystrophy, dominant limb-girdle muscular dystrophy, short-rib thoracic dysplasia, latent short-rib thoracic dysplasia, dominant short-rib thoracic dysplasia, latent short-rib thoracic dysplasia with polydactyly, latent short-rib thoracic dysplasia with retinal dystrophy, mental retardation, truncal obesity, retinal dystrophy, and micropenis (MORM) syndrome, latent MORM syndrome, dominant MORM syndrome, latent retardation with spasticity and retinal degeneration, Cockayne syndrome, latent Cockayne syndrome, dominant Cockayne syndrome, congenital retinal detachment. (nonattachment), latent nonsyndromic congenital retinal detachment, dominant nonsyndromic congenital retinal detachment, hemolytic anemia, nonspherocytic hemolytic anemia, latent nonspherocytic hemolytic anemia, dominant nonspherocytic hemolytic anemia, hereditary neuropathy, hereditary neuropathy (Russian type), latent hereditary neuropathy (Russian type), dominant hereditary neuropathy (Russian type), choroidal sclerosis, latent choroidal sclerosis, dominant choroidal sclerosis, retinopathy, latent retinopathy, dominant retinopathy.Combined dominant and recessive retinopathy, diffuse dominant retinopathy, variable dominant retinopathy, diffuse retinopathy with variable dominant retinopathy, microcephaly, recessive microcephaly, dominant microcephaly, dominant microcephaly with lymphedema, dominant microcephaly with choroidal retinal disease, dominant microcephaly with lymphedema and choroidal retinal disease, choroidal retinal disease, recessive choroidal retinal disease, dominant choroidal retinal disease, choroidal retinal disease with microcephaly, recessive choroidal retinal disease with microcephaly, dominant choroidal retinal disease with microcephaly, renal-coloboma Syndrome, latent renal defect syndrome, overt renal defect syndrome, non-syndromic hearing loss, latent non-syndromic hearing loss, overt non-syndromic hearing loss, cycloidal atrophy, latent cycloidal atrophy, overt cycloidal atrophy, cycloidal choroidal atrophy, vitreoretinal disease, exudative vitreoretinal disease, familial exudative vitreoretinal disease, latent familial exudative vitreoretinal disease, overt familial exudative vitreoretinal disease, overt familial exudative vitreoretinal disease with Kurtz's disease, neovascularization vitreoretinal disease, latent neovascularization vitreoretinal disease, overt neovascularization vitreoretinal disease, atrophic atrophy Areata, latent macular atrophy, overt macular atrophy, Merkel syndrome, latent Merkel syndrome, overt Merkel syndrome, vitreoretinal choroidal disease, latent vitreoretinal choroidal disease, overt vitreoretinal choroidal disease, bestrophinopathy, latent bestrophinopathy, overt bestrophinopathy, high bone mass trait, latent high bone mass trait, overt high bone mass trait, osteoporosis-pseudoglioma syndrome, latent osteoporosis-pseudoglioma syndrome, overt osteoporosis-pseudoglioma Syndrome, microphthalmia, latent microphthalmia, manifest microphthalmia, retinal disease syndrome, latent retinal disease syndrome, manifest retinal disease syndrome, microphthalmia with retinal disease syndrome, latent microphthalmia with retinal disease syndrome, manifest microphthalmia with retinal disease syndrome, true microphthalmia, latent true microphthalmia, manifest true microphthalmia, skeletal dysplasia, latent skeletal dysplasia, manifest skeletal dysplasia, developmental disorder, osteoarthritis with syndromic disorders, cavitary optic disc anomaly, latent cavitary optic disc anomaly, manifest cavitary optic disc anomaly, white spot fundus,Latent white spot fundus, overt white spot fundus, mevalonuria, latent mevalonuria, overt mevalonuria, high IgD syndrome, latent high IgD syndrome, overt high IgD syndrome, spastic paraplegia, latent spastic paraplegia, overt spastic paraplegia, latent spastic paraplegia with neuropathy, latent spastic paraplegia with optic nerve atrophy, latent spastic paraplegia with optic nerve atrophy (dementia) due to neuropathy, latent dementia, overt dementia, familial overt dementia, retinoblastoma, latent retinoblastoma, overt retinoblastoma, germ cell retinoblastoma, somatic cell retinoblastoma, overt germ cell or somatic cell retinoblastoma, retinaculum, benign retinaculum, pineal tumor, osteosarcoma, rod monochromatic vision (rod) Monochromacy, latent rod monochromatic vision, dominant rod monochromatic vision, total color blindness, latent total color blindness, dominant total color blindness, rod total color blindness, rod latent total color blindness, rod dominant total color blindness, latent rod monochromatic vision or total color blindness, pattern dystrophy, latent pattern dystrophy, dominant pattern dystrophy, S-cone syndrome, enhanced S-cone syndrome (ESC), latent ESC, dominant ESC, Goldmann-Favre syndrome Syndrome, latent Goldman-Favre syndrome, dominant Goldman-Favre syndrome, Portinia type malnutrition, latent Portinia type malnutrition, dominant Portinia type malnutrition, white spot retinal degeneration, latent white spot retinal degeneration, dominant white spot retinal degeneration, mucosal storage disease type IIIγ, latent mucosal storage disease type IIIγ, dominant mucosal storage disease type IIIγ, Mainzer-Saldino syndrome, latent Mainzer-Saldino syndrome, dominant Mainzer-Saldino syndrome, elastic pseudoxanthoma, latent elastic pseudoxanthoma, dominant elastic pseudoxanthoma, Knobloch syndrome, latent Knobloch syndrome, dominant Knobloch syndrome, foveal dysplasia, latent foveal dysplasia, dominant foveal dysplasia, anterior segment dysplasia (segmentdysgenesis), recessive anterior segment dysplasia, dominant anterior segment dysplasia, foveal dysplasia with anterior segment dysplasia, recessive foveal dysplasia with anterior segment dysplasia, dominant foveal dysplasia with anterior segment dysplasia, 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 choroidal retinal dystrophy,Latent Boucher-Neuhauser syndrome with choroidal retinal dystrophy, overt Boucher-Neuhauser syndrome with choroidal retinal dystrophy, hypo-pre-β-lipoproteinemia-acanthocytosis-retinitis pigmentosa-palladial (HARP) degeneration, latent HARP degeneration, overt HARP degeneration, Hallewarden-Schpattz syndrome, latent Hallewarden-Schpattz syndrome, overt Hallewarden-Schpattz syndrome, Arager syndrome, latent Arager syndrome, overt Arager syndrome, polyneuropathy-hearing loss-ataxia-retinitis pigmentosa-early-onset cataract (PHARC), latent PHARC, overt PHARC, latent syndromic PHARC, Sorsby's fundus dystrophy), latent Sosby's dystrophy, overt Sosby's dystrophy, vitreoretinal dystrophy, latent vitreoretinal dystrophy, overt vitreoretinal dystrophy, optic neuropathy, latent optic neuropathy, overt optic neuropathy, late-onset overt optic neuropathy, orofacial-finger syndrome type 1, Simpson-Golabi-Behmel syndrome type 2, X-linked retinoschisis, X-linked Oregon ophthalmopathy, X-linked optic atrophy, retinal dysplasia, latent retinal dysplasia, overt retinal dysplasia, X-linked retinal dysplasia, primary X-linked retinal dysplasia, X-linked Norrie's disease, Coulter's disease, X-linked Oran's Island ophthalmopathy, autoimmune inner ear disease (AIED), AIED-like disease, achoroid, X-linked achoroid, neuropathy-optic atrophy-deafness-retinitis pigmentosa Pigmentosa), X-linked neuropathy-optic atrophy-deafness-retinitis pigmentosa, X-linked blue cone monochromacy, X-linked red weakness with rare macular dystrophy in blue cone monochromacy (BCM).X-linked deuteranomaly and rare macular dystrophyin blue cone monochromacy (BCM), including mitochondrial Karns-Sell syndrome (retinitis pigmentosa), Leigh syndrome, retinopathy, mitochondrial retinopathy with sensorineural hearing loss, ocular albinism, oculocutaneous albinism, neuronal ceroid lipofuscin deposition, Zelweg spectrum disorder, cobalamin C deficiency, blue-cone monochromatism, hereditary red-green color vision deficiency, tritan and yellow-blue defect, bradyopsia, delayed cone adaptation, uveitis, diabetic retinopathy, diabetic macular edema, persistent corneal epithelial defects, neurotrophic keratitis, herpetic stromal keratitis, chronic dry eye, glaucoma, ocular abrasion, and ocular bullae formation. blistering, ocular scarring, vision loss, blindness, corneal blindness, dry eye syndrome, aqueous deficiency dry eye disease, Sjögren's syndrome-related aqueous deficiency dry eye, non-Sjögren's syndrome-related dry eye, evaporative dry eye, meibomian gland dysfunction, blepharitis, blepharitis, ocular rosacea and atopy, aqueous deficiency with evaporative dry eye, Fuchs' dystrophy, Fuchs' endothelial dystrophy (FECD), Fuchs' endothelial dystrophy (FED), panuveitis, diffuse uveitis, total uveitis Cataracts, including: partial cataracts, complete cataracts, stationary cataracts, progressive cataracts, hard cataracts, soft cataracts, nuclear cataracts, nuclear sclerotic cataracts, cortical cataracts, posterior subcapsular cataracts, congenital cataracts, corneal dystrophy, epithelial dystrophy with subepithelial dystrophy, epithelial basement membrane dystrophy, recurrent epithelial erosive dystrophy (Franceschetti corneal dystrophy, Dystrophia Smolandiensis and / or Dystrophia Helsinglandica), subepithelial myxoid dystrophy, and Meesmann corneal dystrophy.Lisch epithelial corneal dystrophy, droplet keratopathy, Bowman layer dystrophy, Reis-Bücklers corneal dystrophy, Thiel-Behnke corneal dystrophy, stromal dystrophy-TGFB1 corneal dystrophy, reticular keratopathy, reticular keratopathy type 1 variants (types III, IIIA, I / IIIA, IV), granular keratopathy type 1, granular keratopathy type 2, stromal dystrophy, macular keratopathy, Schneider crystalline keratopathy, congenital stromal keratopathy, punctate keratopathy, posterior amorphous corneal dystrophy, and central cloudy dystrophy of... François, Pre-Descemet corneal dystrophy, endothelial dystrophy, Fuchs dystrophy, polymorphic posterior keratopathy, congenital hereditary endothelial dystrophy, X-linked endothelial dystrophy, superficial superficial dystrophy, epithelial basement membrane dystrophy, Missmann juvenile epithelial dystrophy, droplet keratopathy, Lich epithelial dystrophy, subepithelial mucinous keratopathy, Les-Bukler's keratopathy, Till-Bunk dystrophy, stromal dystrophy, reticular keratopathy, granular keratopathy, macular keratopathy, Schneider crystalline keratopathy, congenital stromal keratopathy, punctate keratopathy, posterior dystrophy The herpesvirus or the drug composition is classified as follows: dystrophy, Fuchs dystrophy, polymorphic posterior keratopathy, congenital hereditary endothelial dystrophy, corneal disease, band keratopathy, corneal band keratopathy, and calcified band keratopathy. In some embodiments, the ocular condition or disease is Staggart syndrome. In some embodiments, the ocular condition or disease is neurotrophic keratitis. In some embodiments, the ocular condition or disease is Leber congenital amaurosis. In some embodiments that can be combined with any of the foregoing embodiments, the subject is a human. In some embodiments that can be combined with any of the foregoing embodiments, the herpesvirus or the drug composition is administered via injection, via injection into the eye, via subretinal injection, via intraocular injection, via intravitreal injection, via suprachoroidal injection, intraocularly, intravitreally, externally, subcutaneously, or subconjunctivally.The medication may be administered to the subject via the subfascial, anterior chamber, retrobulbar, systemic, extra-gastric, perioral, periscleral, anterior periscleral, posterior periscleral, oral, peribulbar, or suprachoroidal routes.

[0020] Other aspects of this disclosure relate to any of the recombinant herpesvirus and / or pharmaceutical compositions described herein for use in treating an eye condition or disease in a subject in need.

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

[0022] In any of the foregoing embodiments, the ocular condition or disease may be selected from retinitis pigmentosa, latent retinitis pigmentosa, severe latent retinitis pigmentosa, overt retinitis pigmentosa, overt retinitis pigmentosa with choroidal involvement, latent retinitis pigmentosa with para-arteriole preserved RPE (PPRPE), latent retinitis pigmentosa with posterior column ataxia (PCARP), latent retinitis pigmentosa with microcytosis, syndromic latent retinitis pigmentosa, latent syndromic disease with retinitis pigmentosa, non-syndromic latent retinitis pigmentosa, non-syndromic overt retinitis pigmentosa, syndromic overt retinitis pigmentosa, juvenile latent retinitis pigmentosa, latent retinitis pigmentosa with Intellectual disability, latent retinitis pigmentosa with macular degeneration, severe early-onset latent retinitis pigmentosa, latent retinitis pigmentosa with skeletal abnormalities, latent retinitis pigmentosa with skeletal deformities, overt retinitis pigmentosa with sensorineural hearing loss, latent retinitis pigmentosa with hearing loss, latent retinitis pigmentosa with hearing loss and other impairments, latent retinitis pigmentosa with vitreous changes, early-onset latent retinitis pigmentosa with macular defects, X-linked retinitis pigmentosa, latent X-linked retinitis pigmentosa, overt X-linked retinitis pigmentosa, severe X-linked retinitis pigmentosa, X-linked retinitis pigmentosa with intellectual disability, X-linked retinitis pigmentosa with myopathy, Bald-Beed Baldr-Biedel syndrome-like retinitis pigmentosa, Baldr-Biedel syndrome-like latent retinitis pigmentosa, bigenic retinitis pigmentosa, bigenic retinitis pigmentosa due to abnormality of outer retinal membrane protein 1, bigenic retinitis pigmentosa due to abnormality of PRPH2, latent retinitis pigmentosa with early macular involvement, latent deafness without retinitis pigmentosa, latent congenital deafness without retinitis pigmentosa, latent retinitis pigmentosa with latent ataxia, latent retinitis pigmentosa with 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 deafness and neurological abnormalities. Systemic abnormalities, autosomal dominant retinitis pigmentosa, non-syndromic 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, Sinier-Lukehn syndrome, recessive Sinier-Lukehn syndrome, dominant Sinier-Lukehn syndrome, renal wasting disease, recessive renal wasting disease, dominant renal wasting disease, juvenile recessive renal wasting disease, ciliopathy-associated recessive renal wasting disease, juvenile renal wasting disease, juvenile recessive renal wasting disease, juvenile dominant renal wasting disease, 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 due to CDH23 abnormality, bigenic Usher syndrome due to PCDH15 abnormality, Acadia recessive Usher syndrome, recessive atypical Usher syndrome (USH3-like), Leber congenital amaurosis, recessive Leber congenital amaurosis Dominant Leber congenital amaurosis, dominant Leber congenital amaurosis, new-onset Leber congenital amaurosis, dominant Leber congenital amaurosis with 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 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, recessive optic atrophy with ataxia and 3-methylpentanoic aciduria, dominant optic atrophy with cataracts, ataxia and areflexia, Kaiser type dominant optic atrophy, dominant optic atrophy with sensorineural hearing loss, recessive cerebellar degeneration with optic atrophy, Optic atrophy with deafness-dystonia syndrome, X-linked optic atrophy with deafness-dystonia syndrome, retinal dystrophy, latent retinal dystrophy, overt retinal dystrophy, hereditary retinal dystrophy, early-onset latent retinal dystrophy, latent syndromic retinal dystrophy, latent non-syndromic retinal dystrophy, latent syndromic and non-syndromic retinal dystrophy, latent optic atrophy with retinal dystrophy, latent retinal dystrophy with obesity, latent retinal dystrophy with cerebellar dysplasia, syndromic latent optic atrophy with retinal dystrophy, overt retinal dystrophy with iris defects, ciliary spectrum disorders including retinal dystrophy, including retinal dystrophy Benign recessive ciliary spectrum disorders, including dominant ciliary spectrum disorders of retinal dystrophy, dominant optic atrophy with neuropathy and myopathy, dominant optic atrophy with intellectual disability and developmental delay, syndromic optic atrophy, non-syndromic optic atrophy, recessive non-syndromic optic atrophy, dominant non-syndromic optic atrophy, recessive syndromic optic atrophy, dominant syndromic optic atrophy, Charcot-Marie-Tuss disease, recessive Charcot-Marie-Tuss disease, dominant Charcot-Marie-Tuss disease, benign punctate retinopathy, recessive benign punctate retinopathy, dominant benign punctate retinopathy, syndromic retinopathy, recessive syndromic retinopathy, dominant syndromic retinopathy, Barten disease, recessive Barten disease, dominant Barten disease.Latent Barten disease (neuronal ceroid lipofuscinosis type 3), juvenile latent Barten disease (neuronal ceroid lipofuscinosis type 3), neuronal ceroid lipofuscinosis, latent neuronal ceroid lipofuscinosis, latent neuronal ceroid lipofuscinosis type 1, dominant neuronal ceroid lipofuscinosis, Staggart disease, latent Staggart disease, dominant Staggart disease, juvenile Staggart disease, late-onset Staggart disease, Staggart disease-like macular dystrophy, latent Staggart disease-like macular dystrophy, dominant Staggart disease-like macular dystrophy, macular dystrophy, latent macular dystrophy, early-onset macular dystrophy, adult-onset macular dystrophy, early-onset latent macular dystrophy, adult-onset latent macular dystrophy, early-onset adult-onset macular dystrophy Human-type latent macular dystrophy, juvenile latent macular dystrophy with sparse hairs, dominant macular dystrophy, late-onset dominant macular dystrophy, dominant macular dystrophy with lens suspensory ligament abnormalities, bull's-eye dominant macular dystrophy, butterfly-shaped dominant macular dystrophy, age-related dominant macular dystrophy, benign concentric ring dominant macular dystrophy, yolk-like latent macular dystrophy, yolk-like dominant macular dystrophy, atypical yolk-like dominant macular dystrophy, dominant adult-type yolk-like macular dystrophy, Stagger's disease-like dominant macular dystrophy, Stagger's disease-type dominant macular dystrophy, North Carolina-type dominant macular dystrophy, North Carolina-type-like dominant macular dystrophy, North Carolina-type-like with progressive sensuality Dominant macular dystrophy, cystoid dominant macular dystrophy, Best type dominant macular dystrophy, occult macular dystrophy, latent occult macular dystrophy, dominant occult macular dystrophy, age-related familial macular dystrophy, X-linked atrophic macular dystrophy, latent X-linked atrophic macular dystrophy, dominant X-linked atrophic macular dystrophy, mitochondrial macular pattern dystrophy with type II diabetes and deafness, xanthomastia, latent xanthomastia, dominant xanthomastia, rod dystrophy, latent rod dystrophy, dominant rod dystrophy, cone dystrophy, latent cone dystrophy, dominant cone dystrophy, latent cone dystrophy Positive enoretinal electroretinogram (ERG) of rods, early-onset latent cone dystrophy, late-onset latent cone dystrophy, cone dystrophy type 1, X-linked cone dystrophy type 1, cone dystrophy type 2, progressive cone dystrophy type 2, X-linked progressive cone dystrophy type 2, delayed cone adaptation, delayed latent cone adaptation, delayed manifest cone adaptation, cone-rod dystrophy, latent cone-rod dystrophy, manifest cone-rod dystrophy, isolated cone-rod dystrophy, progressive cone-rod dystrophy, X-linked cone-rod dystrophy, X-linked progressive cone-rod dystrophy, progressive manifest cone-rod dystrophy, cone-rod dystrophy with enamel hypoplasia syndrome.Latent cone-rod dystrophy with enamel hypoplasia syndrome, dominant cone-rod dystrophy with enamel hypoplasia syndrome, latent cone-rod dystrophy with inner retinal lesions, latent cone-rod dystrophy with skeletal diseases, congenital syndromic non-progressive latent cone-rod dystrophy, latent cone-rod dystrophy with hearing loss, latent cone-rod dystrophy with psychomotor delay, latent cone with cone-rod dystrophy, cone-rod synaptic disorders, congenital cone-rod synaptic disorders, latent congenital cone-rod synaptic disorders, dominant congenital cone-rod synaptic disorders, rod-cone dystrophy, latent cone-rod dystrophy, dominant rod-cone dystrophy, early-onset Latent rod-cone dystrophy, non-syndromic latent rod-cone dystrophy, latent Newfoundland type rod-cone dystrophy, latent progressive cone dystrophy, Stickler syndrome, dominant Stickler syndrome, latent Stickler syndrome, dominant Stickler syndrome type I, dominant Stickler syndrome type II, Marshall syndrome, dominant Marshall syndrome, latent Marshall syndrome, achromatopsia, latent achromatopsia, dominant achromatopsia, latent complete achromatopsia, latent incomplete achromatopsia, 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, latent drusen, dominant Drupial condyloma, early-onset latent drupture, early-onset dominant drupture, macular drupture, dominant radial macular drupture, pigmented paravenous choroidal retinal atrophy, latent pigmented paravenous choroidal retinal atrophy, dominant pigmented paravenous choroidal retinal atrophy, progressive bifocal choroidal retinal atrophy, Balde-Biedel syndrome, latent Balde-Biedel syndrome, dominant Balde-Biedel syndrome, latent Balde-Biedel syndrome with developmental abnormalities, retinal degeneration, latent retinal degeneration, dominant retinal degeneration, non-syndromic latent retinal degeneration, multifactorial celluloid retinal degeneration, latent multifactorial celluloid retinal degeneration, dominant multifactorial celluloid retinal degeneration (Leventinese disease), latent renal wasting disease with retinal Membrane degeneration, Alstrom syndrome, latent Alstrom syndrome, dominant Alstrom syndrome, Jupiter syndrome, latent Jupiter syndrome, dominant Jupiter syndrome, Jobel syndrome, latent Jobel syndrome, dominant Jobel syndrome, X-linked Jobel syndrome, vitreoretinal degeneration, latent vitreoretinal degeneration, dominant vitreoretinal degeneration, snowflake vitreoretinal degeneration, snowflake dominant vitreoretinal degeneration, microstomia, latent microstomia, dominant microstomia, night blindness, stationary night blindness, congenital night blindness, congenital stationary night blindness, severe congenital stationary night blindness, latent congenital stationary night blindness, latent complete congenital stationary night blindness, dominant congenital stationary night blindness.Nogaret type dominant congenital static night blindness, microstomia type latent congenital static night blindness, Riggs type latent congenital static night blindness, Schubert-Bornshain type latent congenital static night blindness, white spot fundus type latent congenital static night blindness, complete latent congenital static night blindness, X-linked congenital static night blindness, incomplete X-linked congenital static night blindness, retinal vascular disease, leukodystrophy, retinal vascular disease with leukodystrophy, latent retinal vascular disease with leukodystrophy, dominant retinal vascular disease with leukodystrophy, Ecardi-Gutier syndrome, Ecardi-Gutier syndrome type 1, latent Ecardi-Gutier syndrome type 1, dominant Ecardi-Gutier syndrome. Erdi-Gutier syndrome type 1, frostbite-like lupus, latent frostbite-like lupus, overt frostbite-like lupus, Martinic retinal dystrophy with retinitis pigmentosa, latent Martinic retinal dystrophy with retinitis pigmentosa, overt Martinic retinal dystrophy with retinitis pigmentosa, spinocerebellar ataxia, latent spinocerebellar ataxia, overt spinocerebellar ataxia, spinocerebellar ataxia with macular dystrophy, spinocerebellar ataxia with retinal degeneration, spinocerebellar ataxia with macular dystrophy or retinal degeneration, latent spinocerebellar ataxia with macular dystrophy or retinal degeneration, overt spinocerebellar ataxia with macular dystrophy or retinal degeneration, Wolfram syndrome Symptoms, Latent Wolveram syndrome, Overt Wolveram syndrome, Low-frequency sensorineural hearing loss, Latent low-frequency sensorineural hearing loss, Overt low-frequency sensorineural hearing loss, Eye and ear syndrome, Latent eye and ear syndrome, Overt eye and ear syndrome, Latent kidney, skeletal and retinal abnormalities, Latent abelasmoproteinemia, Microcephaly, Latent microcephaly, Overt microcephaly, Latent microcephaly with growth retinal disease, Biedi crystalline keratoretinal dystrophy, Latent pedunculated crystalline keratoretinal dystrophy, Overt pedunculated crystalline keratoretinal dystrophy, Wagner's disease, Erosive vitreoretinopathy, Wagner's disease with erosive vitreoretinopathy, Latent Wagner's disease with erosive vitreoretinopathy Overt Wagner's disease with erosive vitreoretinopathy, febrile seizures, latent febrile seizures, overt febrile seizures, overt / latent febrile seizures, choroidal dystrophy, latent choroidal dystrophy, overt choroidal dystrophy, central halo choroidal dystrophy, overt central halo choroidal dystrophy, latent central halo choroidal dystrophy, epiphyseal dysplasia, latent epiphyseal dysplasia, overt epiphyseal dysplasia, multiple epiphyseal dysplasia, latent multiple epiphyseal dysplasia, overt multiple epiphyseal dysplasia, ichthyosis, latent ichthyosis, overt ichthyosis, latent ichthyosis with quadriplegia, choroidal-retinal atrophy, bifocal choroidal-retinal atrophy, progressive bifocal choroidal-retinal atrophy.Latent progressive bifocal chorioretinal atrophy, dominant progressive bifocal chorioretinal atrophy, Rifsum disease, latent Rifsum disease, dominant Rifsum disease, adult latent Rifsum disease, infantile latent Rifsum disease, retinal-cone dystrophy, latent retinal-cone dystrophy, dominant retinal-cone dystrophy, retinal-cone dystrophy type 1, latent retinal-cone dystrophy type 1, dominant retinal-cone dystrophy type 1, blue-yellow color blindness, latent blue-yellow color blindness, dominant blue-yellow color blindness, mucopolysaccharidosis, latent mucopolysaccharidosis, dominant mucopolysaccharidosis, Pinglap achromatopsia, latent Pinglap achromatopsia, dominant Pinglap achromatopsia, Klippel-Fair syndrome, latent Klippel syndrome Per Fell syndrome, dominant Krippel-Fell syndrome, microphthalmia, latent microphthalmia, dominant microphthalmia, limb-girdle muscular dystrophy, latent limb-girdle muscular dystrophy, dominant limb-girdle muscular dystrophy, short-rib thoracic dysplasia, latent short-rib thoracic dysplasia, dominant short-rib thoracic dysplasia, latent short-rib thoracic dysplasia with polydactyly, latent short-rib thoracic dysplasia with retinal dystrophy, intellectual disability-trunk obesity-retinal dystrophy-micropenis (MORM) syndrome, latent MORM syndrome, dominant MORM syndrome, latent retinal delay with spasticity and retinal degeneration, Cockayne syndrome, latent Cockayne syndrome, dominant Cockayne syndrome, congenital retinal detachment, latent nonsyndromic congenital retinal retina Retinal detachment, dominant non-syndromic congenital retinal detachment, hemolytic anemia, nonspherocytic hemolytic anemia, latent nonspherocytic hemolytic anemia, dominant nonspherocytic hemolytic anemia, hereditary neuropathy, hereditary neuropathy (Russian type), latent hereditary neuropathy (Russian type), dominant hereditary neuropathy (Russian type), choroidal sclerosis, latent choroidal sclerosis, dominant choroidal sclerosis, retinopathy, latent retinopathy, dominant retinopathy, dominant and latent combined retinopathy, diffuse dominant retinopathy, variant dominant retinopathy, diffuse retinopathy with variant dominant retinopathy, microcephaly, latent microcephaly, dominant microcephaly, dominant microcephaly with lymphedema, choroidal retina Overt microcephaly due to membranous lesions, overt microcephaly due to lymphedema with choroidal retinal lesions, choroidal retinal lesions, latent choroidal retinal lesions, overt choroidal retinal lesions, choroidal retinal lesions with microcephaly, latent choroidal retinal lesions with microcephaly, overt choroidal retinal lesions with microcephaly, renal defect syndrome, latent renal defect syndrome, overt renal defect syndrome, non-syndromic deafness, latent non-syndromic deafness, overt non-syndromic deafness, cycloplegic atrophy, latent cycloplegic atrophy, overt cycloplegic atrophy, cycloplegic choroidal atrophy, vitreoretinal lesions, exudative vitreoretinal lesions, familial exudative vitreoretinal lesions, latent familial exudative vitreoretinal lesions,Overt familial exudative vitreoretinopathy, overt familial exudative vitreoretinopathy with Kurtz's disease, neovascularization vitreoretinopathy, latent neovascularization vitreoretinopathy, overt neovascularization vitreoretinopathy, macular atrophy, latent macular atrophy, overt macular atrophy, Merkel syndrome, latent Merkel syndrome, overt Merkel syndrome, vitreoretinal choroidal disease, latent vitreoretinal choroidal disease, overt vitreoretinal choroidal disease, yolk sac macular degeneration, latent yolk sac macular degeneration, overt yolk sac macular degeneration, high bone mass trait, latent high bone mass trait, overt high bone mass trait, osteoporosis-pseudoglioma syndrome, latent osteoporosis-pseudoglioma syndrome Glioma syndrome, overt osteoporosis-pseudoglioma syndrome, microphthalmia, latent microphthalmia, overt microphthalmia, retinal disease syndrome, latent retinal disease syndrome, overt retinal disease syndrome, microphthalmia with retinal disease syndrome, latent microphthalmia with retinal disease syndrome, overt microphthalmia with retinal disease syndrome, true microphthalmia, latent true microphthalmia, overt true microphthalmia, skeletal dysplasia, latent skeletal dysplasia, overt skeletal dysplasia, developmental disorders, osteoarthritis with syndromic disorders, cavitary optic disc abnormalities, latent cavitary optic disc abnormalities, overt cavitary optic disc abnormalities, white spot fundus, latent white spot fundus, overt white spot fundus, mevalonateuria, latent mevalonateuria, overt... Mevalonuria, HyperIgD syndrome, Latent hyperIgD syndrome, Overt hyperIgD syndrome, Spastic paraplegia, Latent spastic paraplegia, Overt spastic paraplegia, Latent spastic paraplegia with neuropathy, Latent spastic paraplegia with optic atrophy, Latent spastic paraplegia with optic atrophy (dementia) due to neuropathy, Latent dementia, Overt dementia, Familial overt dementia, Retinoblastoma, Latent retinoblastoma, Overt retinoblastoma, Germ cell retinoblastoma, Somatic cell retinoblastoma, Overt germ cell or somatic cell retinoblastoma, Retinoblastoma, Benign retinoblastoma, Pineal tumor, Osteosarcoma, Rod monochromatic vision, Latent rod monochromatic vision, Overt rod monochromatic vision, Achromatopsia Latent achromatopsia, dominant achromatopsia, rod achromatopsia, rod latent achromatopsia, rod dominant achromatopsia, latent rod monochromatic vision or achromatopsia, figure-like malnutrition, latent figure-like malnutrition, dominant figure-like malnutrition, S-cone syndrome, enhanced S-cone syndrome (ESC), latent ESC, dominant ESC, Goldman-Favre syndrome, latent Goldman-Favre syndrome, dominant Goldman-Favre syndrome, Portinia malnutrition, latent Portinia malnutrition, dominant Portinia malnutrition, white spot retinal degeneration, latent white spot retinal degeneration, dominant white spot retinal degeneration, mucosal storage disease type IIIγ, latent mucosal storage disease type IIIγ, dominant mucosal storage disease type IIIγ.Meinzel-Saldino syndrome, recessive Meinzel-Saldino syndrome, dominant Meinzel-Saldino syndrome, pseudoxanthoma elastica, recessive pseudoxanthoma elastica, dominant pseudoxanthoma elastica, Knobloch syndrome, recessive Knobloch syndrome, dominant Knobloch syndrome, foveal dysplasia, recessive foveal dysplasia, dominant foveal dysplasia, anterior segment dysplasia, recessive anterior segment dysplasia, dominant anterior segment dysplasia, foveal dysplasia with anterior segment dysplasia, recessive foveal dysplasia with anterior segment dysplasia, dominant foveal dysplasia with anterior segment dysplasia, spastic ataxia, recessive spastic ataxia, dominant spastic ataxia, Degroove syndrome, Boucher-Neuhauser syndrome, recessive Boucher-Neuhauser syndrome - Neuhauser syndrome, dominant Boucher-Neuhauser syndrome, Boucher-Neuhauser syndrome with choroidal retinal dystrophy, latent Boucher-Neuhauser syndrome with choroidal retinal dystrophy, dominant Boucher-Neuhauser syndrome with choroidal retinal dystrophy, hypopre-β-lipoproteinemia, acanthosis, retinitis pigmentosa, globus pallidus (HARP) degeneration, latent HARP degeneration, dominant HARP degeneration, Hallewarden-Schpattz syndrome, latent Hallewarden-Schpattz syndrome, dominant Hallewarden-Schpattz syndrome, Arager syndrome, latent Arager syndrome, dominant Arager syndrome, polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, early-onset cataract (PH) ARC), latent PHARC, overt PHARC, latent syndromic PHARC, Sotheby's dystrophy, latent Sotheby's dystrophy, overt Sotheby's dystrophy, vitreoretinal dystrophy, latent vitreoretinal dystrophy, overt vitreoretinal dystrophy, optic neuropathy, latent optic neuropathy, overt optic neuropathy, late-onset overt optic neuropathy, orofacial-finger syndrome type 1, Simpson-Goraby-Bemmell syndrome type 2, X-linked retinoschisis, X-linked Oregon ophthalmopathy, X-linked optic atrophy, retinal dysplasia, latent retinal dysplasia, overt retinal dysplasia, X-linked retinal dysplasia, primary X-linked retinal dysplasia X-linked Norrie disease, Coates' disease, X-linked Isle of Ophthalmopathy, Autoimmune Inner Otopathy (AIED), AIED-like diseases, Achoroidal disease, X-linked Achoroidal disease, Neuropathy-Optical Atrophy-Deafness-Retinitis Pigmentosa, X-linked Neuropathy-Optical Atrophy-Deafness-Retinitis Pigmentosa, X-linked Blue Cone Monochromatic Vision, X-linked Red Weakness with Rare Macular Dystrophy Blue Cone Monochromatic Vision (BCM), X-linked Green Weakness with Rare Macular Dystrophy Blue Cone Monochromatic Vision (BCM), Mitochondrial Karnes-Sell Syndrome including Retinitis Pigmentosa, Leigh syndrome, Retinopathy, Mitochondrial Retinitis Pigmentosa with Sensorineural Hearing Loss, Ocular Albinism, Oculocutaneous AlbinismNeuronal ceroid lipofuscin deposition, Zelweg spectrum disorder, cobalamin C deficiency, blue cone monochromatic vision inherited red-green color vision deficiency, blue blindness with yellow-blue color vision deficiency, visual impairment, delayed cone adaptation, uveitis, diabetic retinopathy, diabetic macular edema, persistent corneal epithelial defects, neurotrophic keratitis, herpetic stromal keratitis, chronic dry eye, glaucoma, ocular abrasion, ocular bullae formation, ocular scarring, vision loss, blindness, corneal blindness, dry eye syndrome, aqueous hypoxic dry eye syndrome, Sjögren's syndrome-related aqueous hypoxic dry eye syndrome, non-Sjögren's syndrome-related dry eye syndrome, evaporative dry eye syndrome, meibomian gland dysfunction, blepharitis, blepharitis, ocular erythema acne with atopic dermatitis, aqueous hypoxic dry eye syndrome with evaporative dry eye syndrome, rich in... Fuchs dystrophy, Fuchs endothelial dystrophy (FECD), Fuchs endothelial dystrophy (FED), panuveitis, diffuse uveitis, complete uveitis, cataract, partial cataract, complete cataract, stationary cataract, progressive cataract, hard cataract, soft cataract, nuclear cataract, nuclear sclerotic cataract, cortical cataract, posterior subcapsular cataract, congenital cataract, corneal dystrophy, epithelial with subepithelial dystrophy, epithelial basement membrane dystrophy, recurrent epithelial erosive dystrophy (Francescatti keratopathy, Smorandi dystrophy and / or Helsinglandia dystrophy), subepithelial myxoid keratopathy, Missmann keratopathy, Lich epithelial keratopathy Malnutrition, droplet keratopathy, Bowman's keratopathy, Les-Buckles keratopathy, Thiel-Bunk keratopathy, stromal dystrophy - TGFB1 keratopathy, reticulate keratopathy, reticulate keratopathy type 1 variants (type III, IIIA, I / IIIA, IV), granular keratopathy type 1, granular keratopathy type 2, stromal dystrophy, macular keratopathy, Schneider crystalline keratopathy, congenital stromal keratopathy, punctate keratopathy, amorphous posterior keratopathy, François central cloud keratopathy, Desmi anterior keratopathy, endothelial dystrophy, Fuchs keratopathy, polymorphism Posterior corneal dystrophy, congenital hereditary endothelial dystrophy, X-linked endothelial dystrophy, superficial corneal dystrophy, epithelial basement membrane dystrophy, Missmann juvenile epithelial dystrophy, droplet keratopathy, Lich epithelial dystrophy, subepithelial mucinous keratopathy, Les-Buckles keratopathy, Thiel-Bunk dystrophy, stromal dystrophy, reticular keratopathy, granular keratopathy, macular keratopathy, Schneider crystalline keratopathy, congenital stromal keratopathy, punctate keratopathy, posterior corneal dystrophy, Fuchs dystrophy, polymorphic posterior corneal dystrophy, congenital hereditary endothelial dystrophy, corneal diseases, band keratopathy,Band keratopathy and calcified band keratopathy. In some embodiments, the ocular condition or disease is Staggart syndrome. In some embodiments, the ocular condition or disease is neurotrophic keratitis. In some embodiments, the ocular condition or disease is Leber congenital amaurosis. In some embodiments that can be combined with any of the foregoing embodiments, the subject is a human. In some embodiments that can be combined with any of the foregoing embodiments, the herpesvirus or the pharmaceutical composition is administered to the subject via injection, via injection into the eye, via subretinal injection, via intraocular injection, via intravitreal injection, intraocular, intravitreal, topical, subcutaneous, subconjunctival, subfascial, anterior chamber, retrobulbar, systemic, parenteral, perioral, near sclera, anterior near sclera, posterior near sclera, oral, perioral, or suprachoroidal administration.

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

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

[0025] Other aspects of this disclosure relate to an article or kit comprising any of the recombinant nucleic acids, viruses, pharmaceuticals and / or pharmaceutical compositions or formulations described herein, and their instructions for use. Attached Figure Description

[0026] Figures 1A-1I illustrate 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 the deletion of the coding sequence for ICP4 (two copies) and expression cassettes containing nucleic acids encoding polypeptides integrated at each ICP4 locus. Figure 1C shows the modified herpes simplex virus genome, which includes the deletion of the coding sequences for ICP4 (two copies) and UL41, and expression cassettes containing nucleic acids encoding polypeptides integrated at each ICP4 locus. Figure 1D shows the modified herpes simplex virus genome, which includes the deletion of the coding sequences for ICP4 (two copies) and UL41, and expression cassettes containing nucleic acids encoding polypeptides integrated at the UL41 locus. Figure 1E shows the modified herpes simplex virus genome, which includes the deletion of the coding sequences for ICP4 (two copies) and ICP22, and expression cassettes containing nucleic acids encoding polypeptides integrated at each ICP4 locus. Figure 1F shows the modified herpes simplex virus genome containing deletions of the coding sequences for ICP4 (two copies) and ICP22, as well as an expression cassette containing a polypeptide-coding nucleic acid integrated at the ICP22 locus. Figure 1G shows the modified herpes simplex virus genome containing deletions of the coding sequences for ICP4 (two copies), UL41, and ICP22, as well as an expression cassette containing a polypeptide-coding nucleic acid integrated at each ICP4 locus. Figure 1H shows the modified herpes simplex virus genome containing deletions of the coding sequences for ICP4 (two copies), UL41, and ICP22, as well as an expression cassette containing a polypeptide-coding nucleic acid integrated at the UL41 locus. Figure 1I shows the modified herpes simplex virus genome containing deletions of the coding sequences for ICP4 (two copies), UL41, and ICP22, as well as an expression cassette containing a polypeptide-coding nucleic acid integrated at the ICP22 locus.

[0027] Figure 2 depicts the vector genome quantification results obtained by qPCR in mouse plasma samples harvested 24 hours after administration of HSV-mCherry in the anterior chamber, choroid, vitreous body, or subretinal. Data are presented as mean ± standard error of the mean (SEM), with n = 3 for each group.

[0028] Figures 3A-3F show the histological results obtained by H&E staining (Figure 3A) and the in vivo expression of the fluorescent reporter 24 hours after HSV-mCherry administration in the anterior chamber (Figures 3B-3F). mCherry (red) was co-stained with DAPI (nuclear marker; blue) and / or N-cadherin (corneal endothelial cell marker; green).

[0029] Figures 4A-4G depict the in vivo expression of the fluorescent reporter 24 hours after application of HSV-mCherry to the choroid (Figures 4A-4F) and the histological results obtained by H&E staining (Figure 4G). mCherry (red) was co-stained with DAPI (nuclear marker; blue), rhodopsin (RHO; photoreceptor marker; green) and / or isomerase / RPE65 (retinal pigment epithelial cell (RPEC) marker; green).

[0030] Figures 5A-5F show the in vivo expression of the fluorescent reporter 24 hours after intravitreal application of HSV-mCherry (Figures 5A-5E) and the histological results obtained by H&E staining (Figure 5F). mCherry (red) was co-stained with DAPI (nuclear marker; blue) and / or N-cadherin (corneal endothelial cell marker; green).

[0031] Figures 6A-6G depict the in vivo expression of the fluorescent reporter 24 hours after subretinal application of HSV-mCherry (Figures 6A-6F) and the histological results obtained by H&E staining (Figure 6G). mCherry (red) was co-stained with DAPI (nuclear marker; blue), rhodopsin (RHO; photoreceptor marker; green) and / or isomerase / RPE65 (retinal pigment epithelial cell (RPEC) marker; green).

[0032] Figures 7A-7D show the levels of genomic DNA (qPCR) and transcripts (qRT-PCR) in primary corneal epithelial cells at 24 hours post-infection (hpi) (Figures 7A-7B) or 48 hours post-infection (hpi) with transgenic herpes simplex virus encoding proNGF (HSV-proNGF; Figures 7A and 7C) or β-NGF (HSV-sNGF; Figures 7B-7D) at a multiplicity of infection (MOI) of 1 or 4. Data indicate cells measured in duplicate and are presented as mean ± standard error of mean (SEM), n = 1.

[0033] Figures 8A-8B depict the Western blot results of human β-NGF in uninfected control cell culture medium (simulated) or in primary corneal epithelial cell culture medium infected with a modified herpes simplex virus (HSV-proNGF) transgene encoding proNGF at a multiplicity of infection (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 marker; Lane 3, simulated; Lane 4, HSV-proNGF MOI 1; Lane 5, HSV-proNGF MOI 4. Figure 8A: 8-10 ng of total protein loaded into lanes 4-5. Figure 8B: 115-140 ng of total protein from concentrated infected primary corneal epithelial cell culture medium loaded into lanes 4-5.

[0034] Figures 9A-9B show human β-NGF secreted from primary corneal epithelial cells at 48 hours post-infection (hpi) with either modified herpes simplex virus encoding proNGF (HSV-proNGF; Figure 9A) or modified herpes simplex virus encoding β-NGF (HSV-sNGF; Figure 9B) transgenes, analyzed by ELISA at a multiplicity of infection (MOI) of 1 or 4. Data indicate cells measured in duplicate, and data are presented as mean ± standard error of mean (SEM), n = 1.

[0035] Figures 10A-10B depict the viability of primary corneal epithelial cells at 24 hours (hpi) or 48 hours post-infection with transgenic herpes simplex virus encoding proNGF (HSV-proNGF; Figure 10A) or β-NGF (HSV-sNGF; Figure 10B) at multiples of infection (MOI) of 0, 0.5, 1, or 3, as analyzed by Mosmann's Tetrazolium Toxicity (MTT). Data indicate cells measured in triplicate and are presented as mean ± standard error of mean (SEM), n = 1.

[0036] Figures 11A-11B show the cell proliferation of TF-1 cells 72 hours after infection with β-NGF-modified herpes simplex virus encoding proNGF (HSV-proNGF; Figure 11A) or β-NGF-modified herpes simplex virus encoding β-NGF (HSV-sNGF; Figure 11B) transgenes (MOI 4) (analyzed by Cell Titer assay). Culture medium and recombinant human β-NGF served as controls only. Data indicate cells measured in triplicate and are presented as mean ± standard error of mean (SEM), n = 1.

[0037] Figures 12A-12C depict the results of corneal fluorescein staining immediately after corneal injury (Figure 12A, 1 mm mechanical corneal injury; Figure 12B, 1 mm deeper mechanical corneal injury penetrating into the stroma; Figure 12C, crossshatch needle scratch corneal injury).

[0038] Figures 13A-13C show the histological results obtained by H&E staining 24 hours after corneal injury and infection with HSV-mCherry (Figure 13A, 1 mm mechanical corneal injury; Figure 13B, 1 mm deeper mechanical corneal injury; Figure 13C, cross-needle scratch corneal injury).

[0039] Figures 14A-14D depict the genome (qPCR; Figures 14A and 14C) and transcripts (qRT-PCR; Figures 14B and 14D) in the corneal epithelium (Figures 14A-14B) or in the whole eye after removal of the corneal epithelium (Figures 14C-14D) 24 hours after topical application of HSV-mCherry to the damaged eye. Data are presented as mean ± standard error of the mean (SEM), with n = 3 eyes per group.

[0040] Figures 15A-15C show the in vivo expression of the fluorescent reporter 24 hours after corneal injury and subsequent topical application of HSV-mCherry (Figure 15A, 1 mm mechanical corneal injury; Figure 15B, 1 mm deeper mechanical corneal injury; Figure 15C, cross-needle scratch corneal injury). mCherry (red) was co-stained with DAPI (nuclear marker; blue).

[0041] Figure 16 depicts HSV-ABCA4 transduction and ABCA4 transgene expression in transduced healthy human ARPE-19 cells (primary retinal pigment epithelial cells). Data are presented as mean ± standard error of the mean (SEM) of duplicate replicates.

[0042] Figure 17 shows dose-dependent (multiple of infection (MOI) of 0 (simulated), 0.05, 0.1, 0.5, 1 or 3) expression of ABCA4 protein in healthy human ARPE-19 cells transduced with HSV-ABCA4.

[0043] Figures 18A-18B depict the results of dose-dependent cytotoxicity assessment in healthy human ARPE-19 cells transduced with HSV-ABCA4 at 24 (Figure 18A) or 48 (Figure 18B) hours post-infection, as analyzed by Mossmann's tetrazolium salt toxicity (MTT) assay. Data are presented as mean ± standard error of the mean (SEM) of three replicates.

[0044] Figures 19A-19C depict the difference in Abca4 levels 24 hours after choroidal injection compared to endogenous ABCA4 in the eyes of wild-type rodents (Figure 19C), from mediator-controlled (Figure 19A) and HSV-ABCA4-treated (Figure 19B) animals. - / - Analysis results of human ABCA4 expression in mouse eyes. Representative images of ABCA4 immunofluorescence (IF) staining in rodent eyes. Two mice treated with HSV-ABCA4 are shown. Insets are imaged at 20x magnification. Cell nuclei are visualized via DAPI staining. ONL = outer nuclear layer.

[0045] Figures 20A-20B show Abca4 from the mediator control (Figure 20A) and HSV-ABCA4 (Figure 20B) 24 hours after injection onto the choroid. - / - Results of co-immunofluorescence staining of mouse eye sections. Abca4 - / - Representative images of IF staining of human ABCA4 (red) and mouse rhodopsin (RHO) (green) in mouse eyes. Insets are imaged at 20x magnification. Cell nuclei are visualized (blue) via DAPI staining. ONL = outer nuclear layer.

[0046] Figures 21A-21H depict the histological results of eye sections from Abca4- / - mice treated with the medium control (Figures 21A and 21E) and HSV-ABCA4 (Figures 21B-21D and 21F-21H) 24 hours after injection into the choroid. Representative images of mouse eyes stained with hematoxylin and eosin (H&E). Figures 21A-21D are imaged at 5x magnification, and Figures 21E-21H at 20x magnification.

[0047] Figures 22A-22C: Slit-lamp photographs of the eye before surgery (Figure 22A) and 8 months after surgery and ophthalmic treatment with HSV-COL7 (Figure 22B). Figure 22C shows anterior segment optical coherence tomography (OCT) images of the corneal epithelium.

[0048] Figure 23 depicts a series of assessment results of the patient's right eye visual acuity after topical application of HSV-COL7. Detailed Implementation

[0049] The following description illustrates exemplary methods, parameters, etc. However, it should be understood that this description is not intended to limit the scope of this disclosure, but is provided as a description of exemplary embodiments. I. General Technology

[0050] The techniques and procedures described or cited herein are generally well understood by those skilled in the art and commonly employed using conventional methods, such as those widely used as described in the following literature: Sambrook et al., Molecular Cloning: A Laboratory Manual 3rd Edition (2001), Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY; Current Protocols in Molecular Biology (edited by FMAusubel et al., (2003)); Methods in Enzymology (Academic Press, Inc.): PCR 2: A Practical Approach (edited by MJ MacPherson, BD Hames, and GR Taylor (1995)), Harlow and Lane (1988); Oligonucleotide Synthesis (edited by MJ Gait, 1984); Methods in Molecular Biology, Humana Press; Cell Biology: A Laboratory Notebook (edited by JE Cellis, 1998), Academic Press; Animal Cell Culture (edited by RIFreshney, 1987); Introduction to Cell and Tissue Culture (JP Mather and PE Roberts, 1998) Plenum Press; Cell and Tissue Culture: Laboratory Procedures (edited by A. Doyle, JB Griffiths and DG Newell, 1993-8) J. Wiley andSons; Gene Transfer Vectors for Mammalian Cells (edited by JM Miller and MP Calos, 1987); PCR: The Polymerase Chain Reaction, (edited by Mullis et al., 1994); ShortProtocols in Molecular Biology (Wiley and Sons, 1999). II. Definition

[0051] Before describing this disclosure in detail, it should be understood that this disclosure is not limited to any particular composition or biological system, which can of course vary. It should also be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting.

[0052] Unless the context clearly specifies otherwise, as used herein, the singular forms “a,” “an,” and “the” include plural indicators. Thus, for example, reference to “a molecule” optionally includes combinations of two or more such molecules, and so on.

[0053] As used herein, the term “and / or” can include any and all combinations of one or more of the relevant listed items. For example, the term “a and / or b” can refer to “a only,” “b only,” “a or b,” or “a and b”; the term “a, b, and / or c” can refer to “a only,” “b only,” “c only,” “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”; and so on.

[0054] As used herein, the term "about" refers to the typical range of error for a corresponding value that is readily known to those skilled in the art. References to "about" a value or parameter herein include (and describe) embodiments involving that value or parameter itself.

[0055] It should be understood that aspects and implementation schemes in this disclosure include “containing aspects and implementation schemes”, “consisting of aspects and implementation schemes”, and “substantially consisting of aspects and implementation schemes”.

[0056] As used herein, the terms “polynucleotide,” “nucleic acid sequence,” “nucleic acid,” and their variants shall be used interchangeably with 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 the polymer contains nucleobases in a configuration that allows base pairing and base stacking), as found in DNA and RNA. Therefore, these terms encompass known types of nucleic acid sequence modifications, such as the substitution of one or more naturally occurring nucleotides with analogs, as well as internucleotide modifications.

[0057] As used herein, when a nucleic acid is positioned to have a functional relationship with another nucleic acid sequence, it is "operatively linked" or "operably linked." For example, if a promoter or enhancer affects the transcription of a coding sequence, it is operatively linked to said sequence; or if a ribosome binding site is located to facilitate translation, it is operatively linked to the coding sequence. Generally, "operatively linked" or "operably linked" means that the linked DNA or RNA is contiguous.

[0058] As used herein, the term "vector" refers to a discrete element used to introduce heterologous nucleic acids into a cell for their expression or replication. Expression vectors include vectors capable of expressing nucleic acids operatively linked to regulatory sequences, such as promoter regions, which enable the expression of such nucleic acids. Thus, expression vectors can refer to DNA or RNA constructs, such as plasmids, bacteriophages, recombinant viruses, or other vectors, that result in the expression of nucleic acids upon introduction into a suitable host cell. Suitable expression vectors are well known to those skilled in the art and include those that are replicable in eukaryotic cells and those that remain free or are integrated into the host cell genome.

[0059] As used in this article, an "open reading frame" or "ORF" refers to a continuous extension of a nucleic acid (DNA or RNA) that encodes a protein or polypeptide. Typically, nucleic acids contain a translation initiation signal or start codon (such as ATG or AUG) and a stop codon.

[0060] As used herein, "untranslated region" or "UTR" refers to untranslated nucleic acid located at the 5' and / or 3' end of an open reading frame. The presence of one or more UTRs in a polynucleotide can affect the post-transcriptional regulation of the polynucleotide, mRNA stability, and / or translation.

[0061] As used herein, the term "transgenic" refers to a polynucleotide that, once introduced into a cell, is transcribed into RNA and translated and / or expressed under appropriate conditions. In some respects, it confers desired properties on the cell into which it is introduced, or otherwise produces desired therapeutic or diagnostic outcomes.

[0062] As used herein, the terms “polypeptide,” “protein,” and “peptide” are used interchangeably and can refer to a polymer of two or more amino acids.

[0063] As used herein, “subject,” “host,” or “individual” means any animal classified as a mammal, including humans; livestock and farm animals; and zoo animals, sporting animals, or pet animals such as dogs, horses, cats, and cattle; and animals used in studies such as mice, rats, hamsters, rabbits, and non-human primates. In some implementations, the mammal is a human.

[0064] As used herein, the terms "pharmaceutical formulation" or "pharmaceutical composition" refer to a preparation which is in a form that enables the biological activity of one or more active ingredients and does not contain any additional components that would have unacceptable toxicity to a subject to which the composition or formulation will be administered. "Pharmaceutically acceptable" excipients (e.g., carriers, additives) are those of the one or more active ingredients employed that can be reasonably administered to a test mammal to provide an effective dose.

[0065] As used herein, an "effective amount" is at least the minimum amount required to affect measurable improvement or prevention of one or more symptoms of a particular disorder. An "effective amount" can vary depending on factors such as the patient's disease state, age, sex, and weight. An effective amount is also the amount in which the beneficial effect of treatment outweighs any toxic or harmful effects of treatment. For prophylactic use, beneficial or desired outcomes include outcomes such as: elimination or reduction of the disease, its complications, and the risk of intermediate pathological phenotypes present during disease development, reduction of its severity, or delay of its onset. For therapeutic use, beneficial or desired outcomes include clinical outcomes such as: reduction of one or more symptoms caused by the disease, improvement of the quality of life of a person with the disease, reduction of the dosage of other agents used to treat symptoms of the disease, delay of disease progression, and / or prolongation of survival. An effective amount can be administered in one or more doses. For the purposes of this disclosure, an effective amount of a recombinant nucleic acid, virus, and / or pharmaceutical composition is an amount sufficient to directly or indirectly achieve prophylactic or therapeutic treatment. As understood in clinical contexts, an effective amount of a recombinant nucleic acid, virus, and / or pharmaceutical composition may or may not be combined with another drug, compound, or pharmaceutical composition to achieve this effect. Therefore, an "effective amount" can be considered when administering one or more therapeutic agents, and if the desired outcome can be achieved, or in combination with one or more other agents, an effective amount of a single agent can be considered.

[0066] As used in this article, “treatment” refers to a clinical intervention designed to alter the natural course of the treated individual or cells during the course of a clinical pathology. Desired therapeutic effects include reducing the rate of disease / disorder / deficiency progression, improving or mitigating the disease / disorder / deficiency state, and alleviating or improving prognosis.

[0067] As used herein, the term "delayed progression of disease / disorder / deficiency" refers to postponing, hindering, slowing, stabilizing, and / or delaying the development of a disease / disorder / deficiency. Such delay can vary in length or duration, depending on the medical history of the disease / disorder / deficiency and / or the individual being treated. As will be apparent to those skilled in the art, a sufficient or significant delay can effectively cover prevention, as the individual does not develop the disease. III. Recombination Core

[0068] Certain aspects of this disclosure relate to recombinant nucleic acids (e.g., isolated recombinant nucleic acids) comprising one or more (e.g., one or more, two or more, three or more, four or more, five or more, ten or more, etc.) polynucleotides 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 the same. In some embodiments, the two or more polypeptides are different.

[0069] In some embodiments, this disclosure relates to recombinant nucleic acids comprising a polynucleotide encoding a chimeric polypeptide, said chimeric polypeptide comprising: a first polypeptide, a linker polypeptide, and a second polypeptide. In some embodiments, the first polypeptide and the second polypeptide are the same. In some embodiments, the first polypeptide and the second polypeptide are different. In some embodiments, the linker polypeptide is a cleavable linker polypeptide. In some embodiments, the linker polypeptide is an uncleavable linker polypeptide.

[0070] In some embodiments, the recombinant nucleic acid is a vector. In some embodiments, the recombinant nucleic acid is a viral vector. In some embodiments, the recombinant nucleic acid is a herpesvirus vector. In some embodiments, the recombinant nucleic acid is a herpes simplex virus amplicon. In some embodiments, the recombinant nucleic acid is a recombinant herpesvirus genome. In some embodiments, the recombinant herpes simplex virus 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. Polynucleotides encoding polypeptides

[0071] In some embodiments, this disclosure relates to recombinant nucleic acids comprising one or more polynucleotides encoding one or more polypeptides (e.g., one or more human polypeptides). Any suitable polypeptide described herein or known in the art may be encoded by the polynucleotides of this disclosure, including, for example, human polypeptides.

[0072] In some embodiments, the polynucleotides of this disclosure comprise the wild-type coding sequence of any gene described herein or known in the art, including any isotype thereof. In some embodiments, the polynucleotides of this disclosure comprise codon-optimized variants of the wild-type coding sequence of any gene described herein or known in the art. In some embodiments, using codon-optimized variants of the coding sequence of a gene increases the stability and / or yield of heterologous expression of the encoded polypeptide (RNA and / or protein) in target cells compared to the stability and / or yield of heterologous expression of the corresponding non-codon-optimized wild-type sequence. Any suitable method known in the art for codon optimization of a sequence for expression in one or more target cells (e.g., one or more human cells) can be used, including, for example, the method described by Fath et al. (PLoS One. March 3, 2011; 6(3): e17596).

[0073] In some embodiments, this disclosure relates to a recombinant nucleic acid comprising one or more polynucleotides containing coding sequences of human genes. Any suitable human gene (including any isotype thereof) known in the art can be encoded by polynucleotides of this disclosure, including, 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), and the DHDDS gene (see, for example, NCBI Gene ID: 79947; SEQ ID NO: 384). NO: 385), PPT1 gene (see, for example, NCBI Gene ID: 5538; SEQ ID NO: 386), ELOVL1 gene (see, for example, NCBI Gene ID: 64834; SEQ ID NO: 387), POMGNT1 gene (see, for example, NCBI Gene ID: 55624; SEQ ID NO: 388), RPE65 gene (see, for example, NCBI Gene ID: 6121; SEQ ID NO: 389), ABCA4 gene (see, for example, NCBI Gene ID: 24; SEQ ID NO: 390), COL11A1 gene (see, for example, NCBI Gene ID: 1301; SEQ ID NO: 391), GNAT2 gene (see, for example, NCBI Gene ID: 2780; SEQ ID NO: 392), CLCC1 gene (see, for example, NCBI Gene ID: 23155; SEQ ID NO: 393), DRAM2 gene (see, for example, NCBI Gene ID: 385), PPT1 gene (see, for example, NCBI Gene ID: 5538; SEQ ID NO: 386), ELOVL1 gene (see, for example, NCBI Gene ID: 64834; SEQ ID NO: 387), POMGNT1 gene (see, for example, NCBI Gene ID: 55624; SEQ ID NO: 388), RPE65 gene (see, for example, NCBI Gene ID: 6121; SEQ ID NO: 389), ABCA4 gene (see, for example, NCBI Gene ID: 24; SEQ ID NO: 390), GOL11A1 gene (see, for example, NCBI Gene ID: 1301; SEQ ID NO: 391), GNAT2 gene (see, for example, NCBI Gene ID SEQ ID: 128338; SEQ ID NO: 394), PRPF3 gene (see, for example, NCBI Gene ID: 9129; SEQ ID NO: 395), ENSA gene (see, for example, NCBI Gene ID: 2029);SEQ ID NO: 396), SEMA4A gene (see, for example, NCBI Gene ID: 64218; SEQ ID NO: 397), ATF6 gene (see, for example, NCBI Gene ID: 22926; SEQ ID NO: 398), HMCN1 gene (see, for example, NCBI Gene ID: 83872; SEQ ID NO: 399), CFH gene (see, for example, NCBI Gene ID: 3075; SEQ ID NO: 400), CRB1 gene (see, for example, NCBI Gene ID: 23418; SEQ ID NO: 401), ADIPOR1 gene (see, for example, NCBI Gene ID: 51094; SEQ ID NO: 402), RD3 gene (see, for example, NCBI Gene ID: 343035; SEQ ID NO: 403), NEK2 gene (see, for example, NCBI Gene ID: 4751; SEQ ID NO: 404), FLVCR1 gene (see, for example, NCBI Gene ID: 396), SEMA4A gene (see, for example, NCBI Gene ID: 64218; SEQ ID NO: 397), ATF6 gene (see, for example, NCBI Gene ID: 22926; SEQ ID NO: 398), HMCN1 gene (see, for example, NCBI Gene ID: 83872; SEQ ID NO: 399), CFH gene (see, for example, NCBI Gene ID: 3075; SEQ ID NO: 400), CRB1 gene (see, for example, NCBI Gene ID: 23418; SEQ ID NO: 401), ADIPOR1 gene (see, for example, NCBI Gene ID: 51094; SEQ ID NO: 402), RD3 gene (see, for example, NC NCBI Gene ID: 28982; SEQ ID NO: 405), USH2A gene (see, for example, NCBI Gene ID: 7399; SEQ ID NO: 406), SDCCAG8 gene (see, for example, NCBI Gene ID: 10806; SEQ ID NO: 407), OR2W3 gene (see, for example, NCBI Gene ID: 343171; SEQ ID NO: 408), NBAS gene (see, for example, NCBI Gene ID: 51594; SEQ ID NO: 409), AGBL5 gene (see, for example, NCBI Gene ID: 60509; SEQ ID NO: 410), ZNF513 gene (see, for example, NCBI Gene ID: 130557; SEQ ID NO: 411), IFT172 gene (see, for example, NCBI Gene ID: 26160; SEQ ID NO: 412), PCARE gene (see, for example, NCBI Gene ID: 388939; SEQ ID NO: 405), USH2A gene (see, for example, NCBI Gene ID: 7399; SEQ ID NO: 406), SDCCAG8 gene (see, for example, NCBI Gene ID: 10806; SEQ ID NO: 407), OR2W3 gene (see, for example, NCBI Gene ID: 343171; SEQ ID NO: 408), NBAS gene (see, for example, NCBI Gene ID: 51594; SEQ ID NO: 409), AGBL5 gene (see, for example, NCBI Gene ID: 60509; SEQ ID NO: 410), ZNF513 gene (see, for example, NCBI Gene ID: 130557; SEQ ID NO: 411), IFT172 gene (see, for 413), EFEMP1 / TLE5 gene (see, for example, NCBI Gene ID: 2202; SEQ ID NO: 414), FAM161A gene (see, for example, NCBI Gene ID: 84140; SEQ ID NO: 415), WDPCP gene (see, for example, NCBI Gene ID: 51057);SEQ ID NO: 416), ALMS1 gene (see, for example, NCBI Gene ID: 7840; SEQ ID NO: 417), SNRNP200 gene (see, for example, NCBI Gene ID: 23020; SEQ ID NO: 418), CNNM4 gene (see, for example, NCBI Gene ID: 26504; SEQ ID NO: 419), CNGA3 gene (see, for example, NCBI Gene ID: 1261; SEQ ID NO: 420), NPHP1 gene (see, for example, NCBI Gene 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: 416), ALMS1 gene (see, for example, NCBI Gene ID: 7840; SEQ ID NO: 417), SNRNP200 gene (see, for example, NCBI Gene ID: 23020; SEQ ID NO: 418), CNNM4 gene (see, for example, NCBI Gene ID: 26504; SEQ ID NO: 419), CNGA3 gene (see, for example, NCBI Gene ID: 1261; SEQ ID NO: 420), NPHP1 gene (see, for example, NCBI Gene 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: 42 424), 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 ID: 6694; SEQ ID NO: 429), TRNT1 gene (see, for example, NCBI Gene ID: 51095; SEQ ID NO: 430), SLC4A7 gene (see, for example, NCBI Gene ID: 9497; SEQ ID NO: 431), LZTFL1 gene (see, for example, NCBI Gene ID: 54585; SEQ ID NO: 432), GNAT1 gene (see, for example, NCBI Gene ID: 54585; SEQ ID NO: 432), GNAT1 gene (see, for example, NCBI Gene ID: 54585; SEQ ID NO: 432), and ...26), and SAG gene (see, for example, NCBI Gene ID: 6295; SEQ ID NO: 428), and SPP2 gene (see, for example, NCBI Gene ID: 6694; SEQ ID NO: 429), and GNAT1 gene (see, for example, NCBI Gene ID: 54060; SEQ ID NO: 425), and GNAT1 gene ( SEQ ID: 2779; SEQ ID NO: 433), TREX1 gene (see, for example, NCBI Gene ID: 11277; SEQ ID NO: 434), MAPKAPK3 gene (see, for example, NCBI Gene ID: 7867; SEQ ID NO: 435), ATXN7 gene (see, for example, NCBI Gene ID: 6314; SEQ ID NO: 436), PROS1 gene (see, for example, NCBI Gene ID: 5627; SEQ ID NO: 433), TREX1 gene (see, for example, NCBI Gene ID: 11277; SEQ ID NO: 434), MAPKAPK3 gene (see, for example, NCBI Gene ID: 7867; SEQ ID NO: 435), ATXN7 gene (see, for example, NCBI Gene ID: 6314; SEQ ID NO: 436), PROS1 gene (SEQ ID NO: 437), ARL6 gene (see, for example, NCBI Gene ID: 84100; SEQ ID NO: 438), IMPG2 gene (see, for example, NCBI Gene ID: 50939; SEQ ID NO: 439), IQCB1 gene (see, for example, NCBI Gene ID: 9657; SEQ ID NO: 440), RHO gene (see, for example, NCBI Gene ID: 6010; SEQ ID NO: 441), NPHP3 gene (see, for example, NCBI Gene ID: 27031; SEQ ID NO: 442), CLRN1 gene (see, for example, NCBI Gene ID: 7401; SEQ ID NO: 443), SLC7A14 gene (see, for example, NCBI Gene ID: 57709; SEQ ID NO: 444), PCYT1A gene (see, for example, NCBI Gene ID: 5130; SEQ ID NO: 445), CEP19 gene (see, for example, NCBI Gene ID: 5130; SEQ ID NO: 445), SEQ ID NO: 445, SEQ ID NO: 437), ARL6 gene (see, for example, NCBI Gene ID: 84100; SEQ ID NO: 438), IMPG2 gene (see, for example, NCBI Gene ID: 50939; SEQ ID NO: 439), IQCB1 gene (see, for example, NCBI Gene ID: 9657; SEQ ID NO: 440), RHO gene (see, for example, NCBI Gene ID: 6010; SEQ ID NO: 441), NPHP3 gene (see, for example, NCBI Gene ID: 27031; SEQ ID NO: 442), SLC7A14 gene (see, for example, NCBI Gene NCBI Gene ID: 84984; SEQ ID NO: 446), PDE6B gene (see, for example, NCBI Gene ID: 5158; SEQ ID NO: 447), WFS1 gene (see, for example, NCBI Gene ID: 7466; SEQ ID NO: 448), HMX1 gene (see, for example, NCBI Gene ID: 3166; SEQ ID NO: 449), RAB28 gene (see, for example, NCBI Gene ID: 9364; SEQ ID NO: 450), CC2D2A gene (see, for example, NCBI Gene ID: 57545; SEQ ID NO: 451), PROM1 gene (see, for example, NCBI Gene ID: 8842; SEQ ID NO: 452), ADGRA3 gene (see, for example, NCBI Gene ID: 166647; SEQ ID NO: 453), DTHD1 gene (see, for example, NCBI Gene ID: 401124; SEQ ID NO: 446), PDE6B gene (see, for example, NCBI Gene ID: 5158; SEQ ID NO: 447), WFS1 gene (see, for example, NCBI Gene ID: 7466; SEQ ID NO: 448), HMX1 gene (see, for example, NCBI Gene ID: 3166; SEQ ID NO: 449), RAB28 gene (see, for example, NCBI Gene ID: 9364; SEQ ID NO: 450), CC2D2A gene (see, for example, NCBI Gene ID: 57545; SEQ ID NO: 451), PROM1 gene (see, for example, NCBI Gene ID: 8842; SEQ ID NO: 452), ADGRA3 gene (see, for example, NCBI Gene ID: 166647 454), WDR19 gene (see, for example, NCBI Gene ID: 57728; SEQ ID NO: 455), CNGA1 gene (see, for example, NCBI Gene ID: 1259; SEQ ID NO: 456), CISD2 gene (see, for example, NCBI Gene ID: 493856; SEQ ID NO: 457), MTTP gene (see, for example, NCBI Gene ID: 4547);SEQ ID NO: 458), LRIT3 gene (see, for example, NCBI Gene ID: 345193; SEQ ID NO: 459), BBS7 gene (see, for example, NCBI Gene ID: 55212; SEQ ID NO: 460), BBS12 gene (see, for example, NCBI Gene ID: 166379; SEQ ID NO: 461), MFSD8 gene (see, for example, NCBI Gene ID: 256471; SEQ ID NO: 462), PLK4 gene (see, for example, NCBI Gene ID: 10733; SEQ ID NO: 463), LRAT gene (see, for example, NCBI Gene ID: 9227; SEQ ID NO: 464), TLR3 gene (see, for example, NCBI Gene ID: 7098; SEQ ID NO: 465), CYP4V2 gene (see, for example, NCBI Gene ID: 285440; SEQ ID NO: 459), LRIT3 gene (see, for example, NCBI Gene ID: 345193; SEQ ID NO: 459 ...BLK4 gene (see, for example, NCBI Gene ID: 55212; SEQ ID NO: 460), BLK4 gene (see, for example, NCBI Gene ID: 285440; SEQ ID NO: 465), BLK4 gene (see, for example, NCBI Gene ID: 285440; SEQ ID NO: 465), BLK4 gene (see, for example, NCBI Gene ID: 466), CWC27 gene (see, for example, NCBI Gene ID: 10283; SEQ ID NO: 467), POC5 gene (see, for example, NCBI Gene ID: 134359; SEQ ID NO: 468), VCAN gene (see, for example, NCBI Gene ID: 1462; SEQ ID NO: 469), ADGRV1 gene (see, for example, NCBI Gene ID: 84059; SEQ ID NO: 470), NR2F1 gene (see, for example, NCBI Gene ID: 7025; SEQ ID NO: 471), SLC25A46 gene (see, for example, NCBI Gene ID: 91137; SEQ ID NO: 472), CTNNA1 gene (see, for example, NCBI Gene ID: 1495; SEQ ID NO: 473), HARS1 gene (see, for example, NCBI Gene ID: 3035; SEQ ID NO: 474), PDE6A gene (see, for example, NCBI... Gene ID: 5145; SEQ ID NO: 475), GRM6 gene (see, for example, NCBI Gene ID: 2916; SEQ ID NO: 476), MAK gene (see, for example, NCBI Gene ID: 4117; SEQ ID NO: 477), C2 gene (see, for example, NCBI Gene ID: 717; SEQ ID NO: 478), CFB gene (see, for example, NCBI Gene ID: 629);SEQ ID NO: 479), TULP1 gene (see, for example, NCBI Gene ID: 7287; SEQ ID NO: 480), GUCA1A gene (see, for example, NCBI Gene ID: 2978; SEQ ID NO: 481), GUCA1B gene (see, for example, NCBI Gene ID: 2979; SEQ ID NO: 482), PRPH2 gene (see, for example, NCBI Gene ID: 5961; SEQ ID NO: 483), IMPG1 gene (see, for example, NCBI Gene ID: 3617; SEQ ID NO: 484), EYS gene (see, for example, NCBI 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; SEQ ID NO: 487), LCA5 gene (see, for example, NCBI Gene ID: 7287; SEQ ID NO: 480 ...PRPH2 gene (see, for example, NCBI Gene ID: 5961; SEQ ID NO: 483), IMPG1 gene (see, for example, NCBI Gene ID: 3617; SEQ ID NO: 484), LYS gene (see, for example, NCBI Gene ID: 346007; SEQ ID NO: 485), LCA5 gene (see, for example, NCBI Gene ID: 1297; SEQ ID NO: 486), RI NCBI Gene ID: 167691; SEQ ID NO: 488), ELOVL4 gene (see, for example, NCBI Gene ID: 6785; SEQ ID NO: 489), PRDM13 gene (see, for example, NCBI Gene ID: 59336; SEQ ID NO: 490), RTN4IP1 gene (see, for example, NCBI Gene ID: 84816; SEQ ID NO: 491), AHI1 gene (see, for example, NCBI Gene ID: 54806; SEQ ID NO: 492), PEX7 gene (see, for example, NCBI Gene ID: 5191; SEQ ID NO: 493), CNOT9 gene (see, for example, NCBI Gene ID: 9125; SEQ ID NO: 494), AHR gene (see, for example, NCBI Gene ID: 196; SEQ ID NO: 495), KLHL7 gene (see, for example, NCBI Gene ID: 55975; SEQ ID NO: 498), NCBI Gene ID: 167691; SEQ ID NO: 488), ELOVL4 gene (see, for example, NCBI Gene ID: 6785; SEQ ID NO: 489), PRDM13 gene (see, for example, NCBI Gene ID: 59336; SEQ ID NO: 490), RTN4IP1 gene (see, for example, NCBI Gene ID: 84816; SEQ ID NO: 491), AHI1 gene (see, for example, NCBI Gene ID: 54806; SEQ ID NO: 492), PEX7 gene (see, for example, NCBI Gene ID: 5191; SEQ ID NO: 493), CNOT9 gene (see, for example, NCBI Gene ID: 9125; SEQ ID NO: 4 496), RP9 gene (see, for example, NCBI Gene ID: 6100; SEQ ID NO: 497), BBS9 gene (see, for example, NCBI Gene ID: 27241; SEQ ID NO: 498), PEX1 gene (see, for example, NCBI Gene ID: 5189; SEQ ID NO: 499), TSPAN12 gene (see, for example, NCBI Gene ID: 23554;SEQ ID NO: 500), IMPDH1 gene (see, for example, NCBI Gene ID: 3614; SEQ ID NO: 501), OPN1SW gene (see, for example, NCBI Gene ID: 611; SEQ ID NO: 502), KIAA1549 gene (see, for example, NCBI Gene ID: 57670; SEQ ID NO: 503), RP1L1 gene (see, for example, NCBI Gene ID: 94137; SEQ ID NO: 504), ADAM9 gene (see, for example, NCBI Gene ID: 8754; SEQ ID NO: 505), HGSNAT gene (see, for example, NCBI Gene ID: 138050; SEQ ID NO: 506), RP1 gene (see, for example, NCBI Gene ID: 6101; SEQ ID NO: 507), TTPA gene (see, for example, NCBI Gene ID: 7274; SEQ ID NO: 508), CSPP1 gene (see, for example, NCBI Gene ID: 500), RP1 ...500), RP1 gene (see, for example, NCBI Gene ID: 500), CSPP1 gene (see, for example, NCBI Gene ID: 500), RP1 gene (see, for example, NCBI Gene ID: 500), CSPP1 gene (see, for example, NCBI Gene ID: 500), RP1 gene (see, for example, NCBI Gene ID: 500), CSPP1 gene (see, for example, NCBI Gene ID: 500), NCBI Gene ID: 79848; SEQ ID NO: 509), OPA1 gene (see, for example, NCBI Gene ID: 4976; SEQ ID NO: 510), PEX2 gene (see, for example, NCBI Gene ID: 5828; SEQ ID NO: 511), CNGB3 gene (see, for example, NCBI Gene ID: 54714; SEQ ID NO: 512), CFAP418 gene (see, for example, NCBI Gene ID: 157657; SEQ ID NO: 513), GDF6 gene (see, for example, NCBI Gene ID: 392255; SEQ ID NO: 514), RIMS2 gene (see, for example, NCBI Gene ID: 9699; SEQ ID NO: 515), KCNV2 gene (see, for example, NCBI Gene ID: 169522; SEQ ID NO: 516), TOPORS gene (see, for example, NCBI Gene ID: 10210; SEQ ID NO: 509), OPA1 gene (see, for example, NCBI Gene ID: 4976; SEQ ID NO: 510), PEX2 gene (see, for example, NCBI Gene ID: 5828; SEQ ID NO: 511), CNGB3 gene (see, for example, NCBI Gene ID: 54714; SEQ ID NO: 512), CFAP418 gene (see, for example, NCBI Gene ID: 157657; SEQ ID NO: 513), GDF6 gene (see, for example, NCBI Gene ID: 392255; SEQ ID NO: 514), RIMS2 gene (see, for example, NCBI Gene ID: 9699; SEQ ID NO: 515), KCNV2 gene (see, for example, NCBI Gene ID: 517), CEP78 gene (see, for example, NCBI Gene ID: 84131; SEQ ID NO: 518), INVS gene (see, for example, NCBI Gene ID: 27130; SEQ ID NO: 519), PRPF4 gene (see, for example, NCBI Gene ID: 9128; SEQ ID NO: 520), WHRN gene (see, for example, NCBI Gene ID: 25861;SEQ ID NO: 521), TRIM32 gene (see, for example, NCBI Gene ID: 22954; SEQ ID NO: 522), TLR4 gene (see, for example, NCBI Gene ID: 7099; SEQ ID NO: 523), DYNC2I2 gene (see, for example, NCBI Gene ID: 89891; SEQ ID NO: 524), PDCD2 gene (see, for example, NCBI Gene ID: 5134; SEQ ID NO: 525), EXOSC2 gene (see, for example, NCBI Gene ID: 23404; SEQ ID NO: 526), ​​INPP5E gene (see, for example, NCBI Gene ID: 56623; SEQ ID NO: 527), PHYH gene (see, for example, NCBI Gene ID: 5264; SEQ ID NO: 528), ACBD5 gene (see, for example, NCBI Gene ID: 91452; SEQ ID NO: 528), SEQ ID NO: 52954, ... 529), PCDH15 gene (see, for example, NCBI Gene ID: 65217; SEQ ID NO: 530), RBP3 gene (see, for example, NCBI Gene ID: 5949; SEQ ID NO: 531), ERCC6 gene (see, for example, NCBI Gene ID: 2074; SEQ ID NO: 532), HK1 gene (see, for example, NCBI Gene ID: 3098; SEQ ID NO: 533), CDH23 gene (see, for example, NCBI Gene ID: 64072; SEQ ID NO: 534), CDHR1 gene (see, for example, NCBI Gene ID: 92211; SEQ ID NO: 535), RGR gene (see, for example, NCBI Gene ID: 5995; SEQ ID NO: 536), KIF11 gene (see, for example, NCBI Gene ID: 3832; SEQ ID NO: 537), RBP4 gene (see, for example, NCBI Gene ID: 5950; SEQ ID NO: 537), PCDH15 gene (see, for example, NCBI Gene ID: 65217; SEQ ID NO: 530), RBP3 gene (see, for example, NCBI Gene ID: 5949; SEQ ID NO: 531), ERCC6 gene (see, for example, NCBI Gene ID: 2074; SEQ ID NO: 532), HK1 gene (see, for example, NCBI Gene ID: 3098; SEQ ID NO: 533), CDH23 gene (see, for example, NCBI Gene ID: 64072; SEQ ID NO: 534), CDHR1 gene (see, for example, NCBI Gene ID: 92211; SEQ ID NO: 535), RGR gene (see, for example, NCBI Gene ID: 538), PDE6C gene (see, for example, NCBI Gene ID: 5146; SEQ ID NO: 539), PAX2 gene (see, for example, NCBI Gene ID: 5076; SEQ ID NO: 540), PDZD7 gene (see, for example, NCBI Gene ID: 79955; SEQ ID NO: 541), ARL3 gene (see, for example, NCBI Gene ID: 403;SEQ ID NO: 542), BBIP1 gene (see, for example, NCBI Gene ID: 92482; SEQ ID NO: 543), ARMS2 gene (see, for example, NCBI Gene ID: 387715; SEQ ID NO: 544), HTRA1 gene (see, for example, NCBI Gene ID: 5654; ​​SEQ ID NO: 545), OAT gene (see, for example, NCBI Gene ID: 4942; SEQ ID NO: 546), ZNF408 gene (see, for example, NCBI Gene ID: 79797; SEQ ID NO: 547), TUB gene (see, for example, NCBI Gene ID: 7275; SEQ ID NO: 548), TEAD1 gene (see, for example, NCBI Gene ID: 7003; SEQ ID NO: 549), USH1C gene (see, for example, NCBI Gene ID: 10083; SEQ ID NO: 550), TMEM216 gene (see, for example, NCBI Gene ID: 542), BBIP1 gene (see, for example, NCBI Gene ID: 92482; SEQ ID NO: 543), ARMS2 gene (see, for example, NCBI Gene ID: 387715; SEQ ID NO: 544), HTRA1 gene (see, for example, NCBI Gene ID: 5654; ​​SEQ ID NO: 545), OAT gene (see, for example, NCBI Gene ID: 4942; SEQ ID NO: 546), ZNF408 gene (see, for example, NCBI Gene ID: 79797; SEQ ID NO: 547), TUB gene (see, for example, NCBI Gene ID: 7275; SEQ ID NO: 548), TMEM216 gene (see, for example, NCBI Gene ID SEQ ID NO: 551), BEST1 gene (see, for example, NCBI Gene ID: 7439; SEQ ID NO: 552), ASRGL1 gene (see, for example, NCBI Gene ID: 80150; SEQ ID NO: 553), ROM1 gene (see, for example, NCBI Gene ID: 6094; SEQ ID NO: 554), BBS1 gene (see, for example, NCBI Gene ID: 582; SEQ ID NO: 555), CABP4 gene (see, for example, NCBI Gene ID: 57010; SEQ ID NO: 556), LRP5 gene (see, for example, NCBI Gene ID: 4041; SEQ ID NO: 557), CAPN5 gene (see, for example, NCBI Gene ID: 726; SEQ ID NO: 558), MYO7A gene (see, for example, NCBI Gene ID: 4647; SEQ ID NO: 558), MYO7A gene (see, for example, NCBI Gene ID: 4647; SEQ ID NO: 559), SEQ ID NO: 551), SEQ ID NO: 552), SEQ ID NO: 553), SEQ ID NO: 554), SEQ ID NO: 555), SEQ ID NO: 556), SEQ ID NO: 557), SEQ ID NO: 558), SEQ ID NO: 559), SEQ ID NO: 559), SEQ ID NO: 552), SEQ ID NO: 553), SEQ ID NO: 554), SEQ ID NO: 555), SEQ ID NO: 555), SEQ ID NO: 556), SEQ ID NO: 557), SEQ ID NO: 558), SEQ ID NO: 559), SEQ ID NO: 559), SEQ ID NO: 55 559), TMEM126A gene (see, for example, NCBI Gene ID: 84233; SEQ ID NO: 560), FZD4 gene (see, for example, NCBI Gene ID: 8322; SEQ ID NO: 561), DYNC2LI1 gene (see, for example, NCBI Gene ID: 51626; SEQ ID NO: 562), CEP164 gene (see, for example, NCBI Gene ID: 22897;SEQ ID NO: 563), C1QTNF5 gene (see, for example, NCBI Gene 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: 563), C1QTNF5 gene (see, for example, NCBI Gene ID: 114902; SEQ ID NO: 564), 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: 565), C1QTNF5 gene (see, for example, NCBI Gene ID: 5959; SEQ ID NO: 565), C1QTNF5 gene (see, for example, NCBI Gene ID: 114902; SEQ ID NO: 564), C1QTNF5 gene (see, for example, NCBI Gene ID: 114902; SEQ ID NO: 565), C1QTNF5 gene (see, for example, NCBI Gene ID: 114902 571), CCT2 gene (see, for example, NCBI Gene ID: 10576; SEQ ID NO: 572), BBS10 gene (see, for example, NCBI Gene ID: 79738; SEQ ID NO: 573), CEP290 gene (see, for example, NCBI Gene ID: 80184; SEQ ID NO: 574), POC1B gene (see, for example, NCBI Gene ID: 282809; SEQ ID NO: 575), MVK gene (see, for example, NCBI Gene ID: 4598; SEQ ID NO: 576), IFT81 gene (see, for example, NCBI Gene ID: 28981; SEQ ID NO: 577), MTRFR gene (see, for example, NCBI Gene ID: 91574; SEQ ID NO: 578), ITM2B gene (see, for example, NCBI Gene ID: 9445; SEQ ID NO: 579), RB1 gene (see, for example, NCBI Gene ID: 10576; SEQ ID NO: 572), CEP290 gene (see, for example, NCBI Gene ID: 80184; SEQ ID NO: 574), POC1B gene (see, for example, NCBI Gene ID: 282809; SEQ ID NO: 575), MVK gene (see, for example, NCBI Gene ID: 4598; SEQ ID NO: 576), RB1 gene (see, for example, NCBI Gene ID: 91574; SEQ ID NO: 578), ITM2B gene (see, for example, NCBI Gene ID: 9445; SEQ ID NO: 579), RB1 gene (see, for example, NCBI Gene ID: 10576; SEQ ID NO: 572), RB1 SEQ ID: 5925; SEQ ID NO: 580), RCBTB1 gene (see, for example, NCBI Gene ID: 55213; SEQ ID NO: 581), GRK1 gene (see, for example, NCBI Gene ID: 6011; SEQ ID NO: 582), RPGRIP1 gene (see, for example, NCBI Gene ID: 57096; SEQ ID NO: 583), NRL gene (see, for example, NCBI Gene ID: 490 ...RNGRIP1 gene (see, for example, NCBI Gene ID: 57096; SEQ ID NO: 583), NSEQ ID NO: 584), OTX2 gene (see, for example, NCBI Gene ID: 5015; SEQ ID NO: 585), RDH11 gene (see, for example, NCBI Gene ID: 51109; SEQ ID NO: 585), RDH12 gene (see, for example, NCBI Gene ID: 145226; SEQ ID NO: 587), TTLL5 gene (see, for example, NCBI Gene ID: 23093; SEQ ID NO: 588), SPATA7 gene (see, for example, NCBI Gene ID: 55812; SEQ ID NO: 589), TTC8 gene (see, for example, NCBI Gene ID: 123016; SEQ ID NO: 590), FBLN5 gene (see, for example, NCBI Gene ID: 10516; SEQ ID NO: 591), TRPM1 gene (see, for example, NCBI Gene ID: 4308; SEQ ID NO: 584), OTX2 gene (see, for example, NCBI Gene ID: 5015; SEQ ID NO: 585), RDH11 gene (see, for example, NCBI Gene ID: 51109; SEQ ID NO: 585), RDH12 gene (see, for example, NCBI Gene ID: 145226; SEQ ID NO: 587), TTLL5 gene (see, for example, NCBI Gene ID: 23093; SEQ ID NO: 588), SPATA7 gene (see, for example, NCBI Gene ID: 55812; SEQ ID NO: 589), TTC8 gene (see, for example, NCBI Gene ID: 123016; SEQ ID NO: 590), FBLN5 gene (see, for example, NCBI Gene ID: 10516; SEQ ID NO: 592), TUBGCP4 gene (see, for example, NCBI Gene ID: 27229; SEQ ID NO: 593), SLC24A1 gene (see, for example, NCBI Gene ID: 9187; SEQ ID NO: 594), NR2E3 gene (see, for example, NCBI Gene ID: 10002; SEQ ID NO: 595), BBS4 gene (see, for example, NCBI Gene ID: 585; SEQ ID NO: 596), CIB2 gene (see, for example, NCBI Gene ID: 10518; SEQ ID NO: 597), RLBP1 gene (see, for example, NCBI Gene ID: 6017; SEQ ID NO: 598), GNPTG gene (see, for example, NCBI Gene ID: 84572; SEQ ID NO: 599), IFT140 gene (see, for example, NCBI Gene ID: 9742; SEQ ID NO: 600), CLUAP1 gene (see, for example, NCBI Gene ID: 9742; SEQ ID NO: 600), CLUAP1 gene (see, for example, NCBI Gene ID: 9187; SEQ ID NO: 594), NR2E3 gene (see, for example, NCBI Gene ID: 10002; SEQ ID NO: 595), BBS4 gene (see, for example, NCBI Gene ID: 585; SEQ ID NO: 596), CIB2 gene (see, for example, NCBI Gene ID: 10518; SEQ ID NO: 597), RLBP1 gene (see, for example, NCBI Gene ID: 6017; SEQ ID NO: 598), GNPTG gene (see, for example, NCBI Gene ID: 84572; SEQ ID NO: 599), IFT140 gene NCBI Gene ID: 23059; SEQ ID NO: 601), ABCC6 gene (see, for example, NCBI Gene ID: 368; SEQ ID NO: 602), CRYM gene (see, for example, NCBI Gene ID: 1428; SEQ ID NO: 603), CLN3 gene (see, for example, NCBI Gene ID: 1201; SEQ ID NO: 604), ZNF423 gene (see, for example, NCBI Gene ID: 23090; SEQ ID NO: 601), ABCC6 gene (see, for example, NCBI Gene ID: 368; SEQ ID NO: 602), CRYM gene (see, for example, NCBI Gene ID: 1428; SEQ ID NO: 603), CLN3 gene (see, for example, NCBI Gene ID: 1201; SEQ ID NO: 604), ZNF4SEQ ID NO: 605), RPGRIP1L gene (see, for example, NCBI Gene ID: 23322; SEQ ID NO: 606), BBS2 gene (see, for example, NCBI Gene ID: 583; SEQ ID NO: 607), ARL2BP gene (see, for example, NCBI Gene ID: 23568; SEQ ID NO: 608), CNGB1 gene (see, for example, NCBI Gene ID: 1258; SEQ ID NO: 609), CDH3 gene (see, for example, NCBI Gene ID: 1001; SEQ ID NO: 610), DHX38 gene (see, for example, NCBI Gene ID: 9785; SEQ ID NO: 611), ADAMTS18 gene (see, for example, NCBI Gene ID: 170692; SEQ ID NO: 612), SLC38A8 gene (see, for example, NCBI Gene ID: 146167; SEQ ID NO: 605), RPGRIP1L gene (see, for example, NCBI Gene ID: 23322; SEQ ID NO: 606), BBS2 gene (see, for example, NCBI Gene ID: 583; SEQ ID NO: 607), ARL2BP gene (see, for example, NCBI Gene ID: 23568; SEQ ID NO: 608), CNGB1 gene (see, for example, NCBI Gene ID: 1258; SEQ ID NO: 609), CDH3 gene (see, for example, NCBI Gene ID: 1001; SEQ ID NO: 610), DHX38 gene (see, for example, NCBI Gene ID: 9785; SEQ ID NO: 611), ADAMTS18 gene (see, for example, NCBI Gene ID: 170692; SEQ ID NO 613), GUCY2D gene (see, for example, NCBI Gene ID: 3000; SEQ ID NO: 614), PRPF8 gene (see, for example, NCBI Gene ID: 10594; SEQ ID NO: 615), AIPL1 gene (see, for example, NCBI Gene ID: 23746; SEQ ID NO: 616), PITPNM3 gene (see, for example, NCBI Gene ID: 83394; SEQ ID NO: 617), UNC119 gene (see, for example, NCBI Gene ID: 9094; SEQ ID NO: 618), GPR179 gene (see, for example, NCBI Gene ID: 440435; SEQ ID NO: 619), MKS1 gene (see, for example, NCBI Gene 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: 3000; SEQ ID NO: 614), GUCY2D gene (see, for example, NCBI Gene ID: 3000; SEQ ID NO: 614), PRPF8 gene (see, for example, NCBI Gene ID: 10594; SEQ ID NO: 615), AIPL1 gene (see, for example, NCBI Gene ID: 23746; SEQ ID NO: 616), PITPNM3 gene (see, for example, NCBI Gene ID: 83394; SEQ ID NO: 617), UNC119 gene (see, for example, NCBI Gene ID: 9094; SEQ ID NO: 618), GPR179 gene (see, for example, NCBI Gene ID: 440435; SEQ ID NO: 61 SEQ 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 ID: 284217; SEQ ID NO: 628), AFG3L2 gene (see, for example, NCBI Gene ID: 10939; SEQ ID NO: 629), CRX gene (see, for example, NCBI Gene ID: 1406; SEQ ID NO: 630), REEP6 gene (see, for example, NCBI Gene ID: 92840; SEQ ID NO: 631), RAX2 gene (see, for example, NCBI Gene ID: 84839; SEQ ID NO: 632), C3 gene (see, for example, NCBI Gene ID: 718; SEQ ID NO: 633), ARHGEF18 gene (see, for example, NCBI Gene ID: 25794; SEQ ID NO: 626 ... AFG3L2 gene (see, for example, NCBI Gene ID: 10939; SEQ ID NO: 629), CRX gene (see, for example, NCBI Gene ID: 7148; SEQ ID NO: 633), ARHGEF18 gene (see, for example, NCBI Gene ID: 25794; SEQ ID NO: 626), AFG3L2 gene (see, for example, NCBI Gene ID: 25794; SEQ ID NO: NCBI Gene ID: 23370; SEQ ID NO: 634), PNPLA6 gene (see, for example, NCBI Gene ID: 10908; SEQ ID NO: 635), RGS9BP gene (see, for example, NCBI Gene ID: 388531; SEQ ID NO: 636), OPA3 gene (see, for example, NCBI Gene ID: 80207; SEQ ID NO: 637), PRPF31 gene (see, for example, NCBI Gene ID: 26121; SEQ ID NO: 638), IDH3B gene (see, for example, NCBI Gene ID: 3420; SEQ ID NO: 639), PANK2 gene (see, for example, NCBI Gene ID: 80025; SEQ ID NO: 640), JAG1 gene (see, for example, NCBI Gene ID: 182; SEQ ID NO: 641), MKKS gene (see, for example, NCBI Gene ID: 8195; SEQ ID NO: 634), PNPLA6 gene (see, for example, NCBI Gene ID: 10908; SEQ ID NO: 635), RGS9BP gene (see, for example, NCBI Gene ID: 388531; SEQ ID NO: 636), OPA3 gene (see, for example, NCBI Gene ID: 80207; SEQ ID NO: 637), PRPF31 gene (see, for example, NCBI Gene ID: 26121; SEQ ID NO: 638), IDH3B gene (see, for example, NCBI Gene ID: 3420; SEQ ID NO: 639), PANK2 gene (see, for example, NCBI Gene ID: 80025; SEQ ID NO: 640), JAG1 gene (see, for example, NCBI Gene ID: 1 642), KIZ gene (see, for example, NCBI Gene ID: 55857; SEQ ID NO: 643), ABHD12 gene (see, for example, NCBI Gene ID: 26090; SEQ ID NO: 644), KIF3B gene (see, for example, NCBI Gene ID: 9371; SEQ ID NO: 645), CEP250 gene (see, for example, NCBI Gene ID: 11190;SEQ ID NO: 646), PRPF6 gene (see, for example, NCBI Gene ID: 24148; SEQ ID NO: 647), CFAP410 gene (see, for example, NCBI Gene ID: 755; SEQ ID NO: 648), DNM1L gene (see, for example, NCBI Gene ID: 10059; SEQ ID NO: 649), TIMP3 gene (see, for example, NCBI Gene ID: 7078; SEQ ID NO: 650), IFT27 gene (see, for example, NCBI Gene ID: 11020; SEQ ID NO: 651), FBLN1 gene (see, for example, NCBI Gene ID: 2192; SEQ ID NO: 652), MIEF1 gene (see, for example, NCBI Gene ID: 2192; SEQ ID NO: 652), ACO2 gene (see, for example, NCBI Gene ID: 50; SEQ ID NO: 654), TUBGCP6 gene (see, for example, NCBI Gene ID: 50; SEQ ID NO: 654), PCRAP410 gene (see, for example, NCBI Gene ID: 755; SEQ ID NO: 648), DNM1L gene (see, for example, NCBI Gene ID: 10059; SEQ ID NO: 649), TIMP3 gene (see, for example, NCBI Gene ID: 7078; SEQ ID NO: 650), IFT27 gene (see, for example, NCBI Gene ID: 11020; SEQ ID NO: 651), FIMP2 gene (see, for example, NCBI Gene ID: 2192; SEQ ID NO: 652), MIEF1 gene (see, for example, NCBI Gene ID: 2192; SEQ ID NO: 652), NCBI Gene ID: 85378; SEQ ID NO: 655), OFD1 gene (see, for example, NCBI Gene ID: 8481; SEQ ID NO: 656), RS1 gene (see, for example, NCBI Gene ID: 6247; SEQ ID NO: 657), RP2 gene (see, for example, NCBI Gene ID: 6102; SEQ ID NO: 658), DMD gene (see, for example, NCBI Gene ID: 1756; SEQ ID NO: 659), RPGR gene (see, for example, NCBI Gene ID: 6103; SEQ ID NO: 660), NYX gene (see, for example, NCBI Gene ID: 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: 85378; SEQ ID NO: 655), OFD1 gene (see, for example, NCBI Gene ID: 8481; SEQ ID NO: 656), RS1 gene (see, for example, NCBI Gene ID: 6247; SEQ ID NO: 657), RP2 gene (see, for example, NCBI Gene ID: 6102; SEQ ID NO: 658), DMD gene (see, for example, NCBI Gene ID: 1756; SEQ ID NO: 659), RPGR gene (see, for example, NCBI Gene ID: 6103; SEQ ID NO: 660), NYX gene (see, for example, NCBI Gene ID: 60506; SEQ ID NO: 661), PEPD gene (see, for SEQ 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 NO: 669), OPN1MW gene (see, for example, NCBI Gene ID: 2652; SEQ ID NO: 670), OPN1SW gene (see, for example, NCBI Gene ID: 611; SEQ ID NO: 671), TFAM gene (see, for example, NCBI Gene ID: 7019; SEQ ID NO: 672), MT-ND1 gene (see, for example, NCBI Gene ID: 4535; SEQ ID NO: 673), MT-ND2 gene (see, for example, NCBI Gene ID: 4536; SEQ ID NO: 674), MT-ND3 gene (see, for example, NCBI Gene ID: 4537; SEQ ID NO: 675), MT-ND4L gene (see, for example, NCBI Gene ID: 5631; SEQ ID NO: 668), PRPS1 gene (see, for example, NCBI Gene ID: 5631; SEQ ID NO: 668), OPN1LW gene (see, for example, NCBI Gene ID: 5956; SEQ ID NO: 669), OPN1MW gene (see, for example, NCBI Gene ID: 2652; SEQ ID NO: 670), MT-ND4L gene (see, for example, NCBI Gene ID: 611; SEQ ID NO: 671), MT-ND2 gene (see, for example, NCBI Gene ID: 4536; SEQ ID NO: 674), MT-ND3 gene (see, for example, NCBI Gene ID: 4537; SEQ ID NO: 67 MT-ND4 gene (see, for example, NCBI Gene ID: 4538; SEQ ID NO: 677), MT-ND5 gene (see, for example, NCBI Gene ID: 4540; SEQ ID NO: 678), MT-ND6 gene (see, for example, NCBI Gene ID: 4541; SEQ ID NO: 679), MT-ATP6 gene (see, for example, NCBI Gene ID: 4508; SEQ ID NO: 680), MT-ATP8 gene (see, for example, NCBI Gene ID: 4509; SEQ ID NO: 681), MT-CO1 gene (see, for example, NCBI Gene ID: 4512; SEQ ID NO: 682), MT-CO3 gene (see, for example, NCBI Gene ID: 4514; SEQ ID NO: 683), MT-CYB gene (see, for example, NCBI Gene ID: 4519; SEQ ID NO: 676), MT-ND4 gene (see, for example, NCBI Gene ID: 4538; SEQ ID NO: 677), MT-ND5 gene (see, for example, NCBI Gene ID: 4540; SEQ ID NO: 678), MT-ND6 gene (see, for example, NCBI Gene ID: 4541; SEQ ID NO: 679), MT-ATP6 gene (see, for example, NCBI Gene ID: 4508; SEQ ID NO: 680), MT-ATP8 gene (see, for example, NCBI Gene ID: 4509; SEQ ID NO: 681), MT-CO1 gene (see, for example, NCBI Gene ID: 4512; SEQ ID NO: 682), MT-CO3 gene (see, for example, NCBI Gene ID: 4514; SEQ ID NO: 683), 684), LARS2 gene (see, for example, NCBI Gene ID: 23395; SEQ ID NO: 685), EARS2 gene (see, for example, NCBI Gene ID: 124454; SEQ ID NO: 686), KARS1 gene (see, for example, NCBI Gene ID: 3735; SEQ ID NO: 687), HARS2 gene (see, for example, NCBI Gene ID: 23438);SEQ ID NO: 688), SARS2 gene (see, for example, NCBI Gene ID: 54938; SEQ ID NO: 689), PARS2 gene (see, for example, NCBI Gene ID: 25973; SEQ ID NO: 690), MMACHC gene (see, for example, NCBI Gene ID: 25974; SEQ ID NO: 691), POU3F4 gene (see, for example, NCBI Gene ID: 5456; SEQ ID NO: 692), RPS6KA6 gene (see, for example, NCBI Gene ID: 27330; SEQ ID NO: 693), CPLANCE1 gene (see, for example, NCBI Gene ID: 65250; SEQ ID NO: 694), TMEM67 gene (see, for example, NCBI Gene ID: 91147; SEQ ID NO: 695), TRAF3IP1 gene (see, for example, NCBI Gene ID: 26146; SEQ ID NO: 688), SARS2 gene (see, for example, NCBI Gene ID: 54938; SEQ ID NO: 689), PARS2 gene (see, for example, NCBI Gene ID: 25973; SEQ ID NO: 690), MMACHC gene (see, for example, NCBI Gene ID: 25974; SEQ ID NO: 691), POU3F4 gene (see, for example, NCBI Gene ID: 5456; SEQ ID NO: 692), RPS6KA6 gene (see, for example, NCBI Gene ID: 27330; SEQ ID NO: 693), TMEM67 gene (see, for example, NCBI Gene ID: 91147; SEQ ID NO: 695), TRAF3IP1 gene (see, for example, NCBI Gene ID: 26146; SEQ ID 696), IFT74 gene (see, for example, NCBI Gene ID: 80173; SEQ ID NO: 697), SCAPER gene (see, for example, NCBI Gene ID: 49855; SEQ ID NO: 698), SCLT1 gene (see, for example, NCBI Gene ID: 132320; SEQ ID NO: 699), KIAA0586 gene (see, for example, NCBI Gene ID: 9786; SEQ ID NO: 700), TCTN2 gene (see, for example, NCBI Gene ID: 79867; SEQ ID NO: 701), ARL13B gene (see, for example, NCBI Gene ID: 200894; SEQ ID NO: 702), B9D1 gene (see, for example, NCBI Gene ID: 27077; SEQ ID NO: 703), B9D2 gene (see, for example, NCBI Gene ID: 80776; SEQ ID NO: 697), IFT74 gene (see, for example, NCBI Gene ID: 80173; SEQ ID NO: 697), SCAPER gene (see, for example, NCBI Gene ID: 49855; SEQ ID NO: 698), SCLT1 gene (see, for example, NCBI Gene ID: 132320; SEQ ID NO: 699), KIAA0586 gene (see, for example, NCBI Gene ID: 9786; SEQ ID NO: 700), TCTN2 gene (see, for example, NCBI Gene ID: 79867; SEQ ID NO: 701), SCLT1 gene (see, for example, NCBI Gene ID: 80776; SEQ ID NO: 702), SCLT1 gene (see, for example, NCBI Gene ID: 27077; 704), C2CD3 gene (see, for example, NCBI Gene 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 NO: 712), TCTN1 gene (see, for example, NCBI Gene ID: 79600; SEQ ID NO: 713), TCTN3 gene (see, for example, NCBI Gene ID: 26123; SEQ ID NO: 714), TMEM107 gene (see, for example, NCBI Gene ID: 84314; SEQ ID NO: 715), TMEM138 gene (see, for example, NCBI Gene ID: 51524; SEQ ID NO: 709), NCBI Gene ID: 23247; SEQ ID NO: 710 ... NCBI Gene ID: 23247; SEQ ID NO: 710), NCBI Gene ID: 23247; SEQ ID NO: 710), NCBI Gene ID: 23247; SEQ ID NO: 710), NCBI Gene ID: 23247; SEQ ID NO: 710), NCBI Gene ID: 23247; SEQ ID NO: 716), TMEM231 gene (see, for example, NCBI Gene ID: 79583; SEQ ID NO: 717), TTC21B gene (see, for example, NCBI Gene ID: 79809; SEQ ID NO: 718), RORA gene (see, for example, NCBI Gene ID: 6095; SEQ ID NO: 719), NGF gene (see, for example, NCBI Gene ID: 4803; SEQ ID NO: 720), COL8A2 gene (see, for example, NCBI Gene ID: 1296; SEQ ID NO: 721), SLC4A11 gene (see, for example, NCBI Gene ID: 83959; SEQ ID NO: 722), ZEB1 gene (see, for example, NCBI Gene ID: 6935; SEQ ID NO: 723), KRT83 gene (see, for example, NCBI Gene ID: 3889; SEQ ID NO: 724), KRT12 gene (see, for example, NCBI Gene ID: 79583; SEQ ID NO: 717), TTC21B gene (see, for example, NCBI Gene ID: 79809; SEQ ID NO: 718), RORA gene (see, for example, NCBI Gene ID: 6095; SEQ ID NO: 719), NGF gene (see, for example, NCBI Gene ID: 4803; SEQ ID NO: 720), COL8A2 gene (see, for example, NCBI Gene ID: 1296; SEQ ID NO: 721), SLC4A11 gene (see, for example, NCBI Gene ID: 83959; SEQ ID NO: 722), KRT83 gene (see, for example, NCBI Gene ID: 3889; SEQ ID NO: 724), KRT1 SEQ ID: 3859; SEQ ID NO: 725), TGFBI gene (see, for example, NCBI Gene ID: 7045; SEQ ID NO: 726), TACSTD2 gene (see, for example, NCBI Gene ID: 4070; SEQ ID NO: 727), CHST6 gene (see, for example, NCBI Gene ID: 4166; SEQ ID NO: 728), GSN gene (see, for example, NCBI Gene ID: 2934; SEQ ID NO: 725), TGFBI gene (see, for example, NCBI Gene ID: 3859; SEQ ID NO: 725), TGFBI gene (see, for example, NCBI Gene ID: 7045; SEQ ID NO: 726), TACSTD2 gene (see, for example, NCBI Gene ID: 4070; SEQ ID NO: 727), CHST6 gene (see, for example,SEQ ID NO: 729), UBIAD1 gene (see, for example, NCBI Gene ID: 29914; SEQ ID NO: 730), DCN gene (see, for example, NCBI Gene ID: 1634; SEQ ID NO: 731), PIKFYVE gene (see, for example, NCBI Gene ID: 200576; SEQ ID NO: 732), OVOL2 gene (see, for example, NCBI Gene ID: 58495; SEQ ID NO: 733), GRHL2 gene (see, for example, NCBI Gene ID: 79977; SEQ ID NO: 734), etc. In some embodiments, the polynucleotides in this disclosure comprise 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 with any gene (and / or its coding sequence) described herein or known in the art.

[0074] In some embodiments, the polynucleotide of this disclosure encodes a β-nerve growth factor polypeptide. 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 the 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 the sequence of SEQ ID NO: 363. In some embodiments, the polynucleotide encoding the β-nerve growth factor polypeptide is a polynucleotide encoding a polypeptide comprising the amino acid sequence of SEQ ID NO: 363.

[0075] In some embodiments, the polynucleotide of this disclosure encodes a β-nerve growth factor polypeptide. 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 the 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 the sequence of SEQ ID NO: 739. In some embodiments, the polynucleotide encoding the β-nerve growth factor polypeptide is a polynucleotide encoding a polypeptide comprising the amino acid sequence of SEQ ID NO: 739.

[0076] In some embodiments, the polynucleotide of this disclosure encodes a β-nerve growth factor polypeptide. 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 the 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 the sequence of SEQ ID NO: 740. In some embodiments, the polynucleotide encoding the β-nerve growth factor polypeptide is a polynucleotide encoding a polypeptide comprising the amino acid sequence of SEQ ID NO: 740.

[0077] In some embodiments, the polynucleotide encoding the β-nerve growth factor polypeptide is an N-terminal truncated, C-terminal truncated, or fragmented polynucleotide encoding the amino acid sequence of SEQ ID NO:363, SEQ ID NO:739, and / or SEQ ID NO:740. The N-terminal truncated, C-terminal truncated, or fragmented polynucleotide may comprise 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 but less than 241 consecutive amino acids from SEQ ID NO:363, SEQ ID NO:739, and / or SEQ ID NO:740.

[0078] In some embodiments, the polynucleotide of this disclosure encodes a retinal-specific phospholipid transporter ATPase polypeptide. In some embodiments, the retinal-specific phospholipid transporter ATPase polypeptide is a human retinal-specific phospholipid transporter 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 retinal-specific phospholipid transporter 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 the sequence of SEQ ID NO: 33. In some embodiments, the polynucleotide encoding the retinal-specific phospholipid transport ATPase polypeptide is a polynucleotide encoding a polypeptide containing the amino acid sequence of SEQ ID NO: 33.

[0079] In some embodiments, the polynucleotide encoding the retinal-specific phospholipid transporter ATPase polypeptide is a polynucleotide encoding an N-terminal truncated, C-terminal truncated, or fragmented amino acid sequence of SEQ ID NO: 33. The N-terminal truncated, C-terminal truncated, or fragmented polynucleotide may comprise 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 but less than 2,273 consecutive amino acids of SEQ ID NO: 33.

[0080] In some embodiments, the polynucleotide of this disclosure encodes a 290 kDa centrosomal protein polypeptide. In some embodiments, the 290 kDa centrosomal protein polypeptide is a human 290 kDa centrosomal protein 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 GeneID: 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 290 kDa centrosomal protein 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 the sequence of SEQ ID NO: 217. In some embodiments, the polynucleotide encoding a 290 kDa centrosome protein polypeptide is a polynucleotide encoding a polypeptide containing the amino acid sequence of SEQ ID NO: 217.

[0081] In some embodiments, the polynucleotide encoding the 290 kDa centrosomal protein polypeptide is an N-terminal truncated, C-terminal truncated, or fragmented polynucleotide encoding the amino acid sequence of SEQ ID NO:217. The N-terminal truncated, C-terminal truncated, or fragmented polynucleotide may comprise 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 but less than 2,479 consecutive amino acids of SEQ ID NO:217.

[0082] In some embodiments, the polynucleotide of this disclosure encodes a polypeptide. In some embodiments, the polypeptide is a human polypeptide. In some embodiments, the polynucleotide comprises a coding sequence of a wild-type gene (see, for example, SEQ ID NO: 378-734) or a codon-optimized variant thereof (see, for example, SEQ ID NO: 735-738 and / or SEQ ID NO: 741-743). In some embodiments, the polynucleotide encoding the 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 polynucleotide encodings of this disclosure comprise polypeptides containing amino acid sequences selected from SEQ ID NO: 21-377 and / or SEQ ID NO: 739-740.

[0083] In some embodiments, the polynucleotide encoding the polypeptide is an N-terminal truncated, C-terminal truncated, or fragmented polynucleotide encoding an amino acid sequence selected from SEQ ID NO: 21-377 and / or SEQ ID NO: 739-740. The N-terminal truncated, C-terminal truncated, or fragmented polynucleotide may comprise, 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, at least 400, etc., consecutive amino acids selected from SEQ ID NO: 21-377 and / or SEQ ID NO: 739-740.

[0084] In some embodiments, the polynucleotides of this disclosure encode any one or more of the following in any suitable combination: In some embodiments that can be combined with any of the foregoing embodiments, the polypeptide is selected from protein 11 containing the sterility α motif domain, renal cyst protein 4, espin, nicotinamide / nicotinic acid mononucleotide adenosyltransferase 1, mitochondrial fusion protein 2, endoplasmic reticulum membrane protein complex subunit 1, group V phospholipase A2, dehydrogenase-6-phosphate synthase complex subunit, palmitoyl protein thioesterase 1, very long chain fatty acid elongation protein 1, protein O-linked mannose β-1,2-N-acetylglucosamine aminotransferase 1, retinoid isomerase, retinal-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-regulating autophagy regulator protein 2, U4 / U6 Small nucleoribonucleoprotein Prp3, α-sulfonamide, signaling 4A, cyclic AMP-dependent transcription factor ATF-6α, hemicentin-1, complement factor H, crumbs protein homolog 1, adiponectin receptor protein 1, RD3 protein, serine / threonine protein kinase Nek2, feline leukemia virus C subset receptor-associated protein 1, Usherin, serologically defined colon cancer antigen 8, olfactory receptor 2W3, NBAS subunit of NRZ tethering complex, cytoplasmic carboxypeptidase-like protein 5, zinc finger protein 513, flagellated transporter 172 homolog, photoreceptor ciliary actin regulator, EGF-containing fibula protein-like extracellular matrix protein 1 / TLE family member 5, FAM161A protein, planar cell polar effector protein fritz homolog containing WD repeat sequence, centrosome-associated protein ALMS1, U5 small nucleoribonucleoprotein 200 kDa helicase, metallotransferase CNNM4, cyclic nucleotide-gated cation channel α-3, renal cystin 1, tyrosine protein kinase Mer, Baldr-Biedel syndrome-associated protein 5, ceramide kinase-like protein, neurogenic differentiation factor 1, transmembrane protein 237, inward rectifier potassium channel 13, S-repressor protein, secretory phosphoprotein 24, mitochondrial CCA tRNA nucleotide transferase 1, sodium bicarbonate cotransporter 3, leucine zipper transcription factor-like protein 1, guanine nucleotide-binding protein G(t) subunit α-1, 3' repair exonuclease 1, MAP kinase-activated protein kinase 3, ataxia protein 7, vitamin K-dependent protein S, ADP riboylation factor-like protein 6, photoreceptor interstitial proteoglycan 2, IQ-containing calmodulin-binding motif protein 1, rhodopsin, renal cystin 3, Clarin-1, possible cation amino acid transporter / solute carrier family 7 member 14, phosphocholine cytyltransferase A, 19 kDa centrosomal protein, rod cGMP-specific 3',5'-cyclic nucleotide phosphodiesterase subunit β, Wolframin, and homeobox protein HMX1Ras-related proteins Rab-28, protein 2A containing a coiled-coil C2 domain, Prominin-1, adhesion G protein-coupled receptor A3, protein 1 containing a death domain, protein 19 containing a WD repeat sequence, cGMP-gated cation channel α-1, protein 2 containing a CDGSH iron-sulfur domain, large subunit of microsomal triglyceride transporter, protein 3 containing a leucine-rich repeat sequence, immunoglobulin-like domain, and transmembrane domain, Baldr-Biedel syndrome-related protein 7, Baldr-Biedel syndrome-related protein 12, protein 8 containing a major facilitated superfamily domain, serine / threonine protein kinase PLK, lecithin retinyl acyltransferase, Toll-like receptor 3, cytochrome P450. 4V2, spliceosome-associated protein CWC27 homolog, centrosome protein POC5, multifunctional proteoglycan core protein, adhesion G protein-coupled receptor V1, COUP transcription factor 1, mitochondrial outer membrane protein SLC25A46, catalin α-1, cytoplasmic histidine-tRNA ligase, rod cGMP-specific 3',5'-cyclic nucleotide phosphodiesterase subunit α, metabolite glutamate receptor 6, serine / threonine protein kinase MAK, complement C2, complement factor B, Tubby-associated protein 1, guanylate cyclase activator 1, guanylate cyclase activator 2, peripheral protein 2, photoreceptor intercellular matrix proteoglycan 1, eyes Shut protein homolog, collagen α-1 (IX) chain, regulatory synaptic exocytogenin 1, Lebercilin, very long chain fatty acid elongation protein 4, PR domain zinc finger protein 13, mitochondrial reticulin 4 interacting protein 1, Jouberin, peroxisome guide signal 2 receptor, CCR4-NOT transcription complex subunit 9, aryl hydrocarbon receptor, Kelch-like protein 7, retinitis pigmentosa type 9 protein, PTHB1 protein, peroxisome ATPase PEX1, tetratransmembrane protein 12, inosine-5'-monophosphate dehydrogenase 1, short-wavelength sensitive opsin 1, UPF0606 protein KIAA1549, retinitis pigmentosa type 1 protein-like 1 protein, protein containing detegrin metalloproteinase domain 9, heparin-α-aminoglycine N-acetyltransferase, oxygen regulator protein 1, α-tocopherol transporter, centrosome and spindle polar-associated protein 1, mitochondrial activator protein-like 120 kDa protein, peroxisome biogenesis factor 2, cyclic nucleotide-gated cation channel β-3, ciliary and flagella-associated protein 418, growth differentiation factor 6, regulatory synaptic exocytogenin 2, voltage-gated potassium channel subfamily V member 2, E3 ubiquitin-protein ligases Topors, 78 kDa centrosomal protein, Inversin, U4 / U6 small nucleoribonucleoprotein Prp4, Whirlin, 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 type IV polyphosphate 5-phosphatase, peroxisome phytyl-CoA dioxygenase, 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, kinin-like protein KIF11, retinol-binding protein 4, cone cGMP-specific 3',5'-cyclic nucleotide phosphodiesterase subunit α, pairing box protein Pax-2, PDZ-domain-containing protein 7, ADP-ribosylation factor-like protein 3, BBSome interaction The following proteins were used: protein 1, age-related macular degeneration susceptibility protein 2, serine protease HTRA1, mitochondrial ornithine aminotransferase, zinc finger protein 408, Tubby protein homolog, transcription enhancer TEF-1, Harmonin, transmembrane protein 216, Bestrophin-1, isaspartate peptidase / L-asparaginase, outer rod membrane protein 1, Baldr-Biedel syndrome-associated protein 1, calcium-binding protein 4, low-density lipoprotein receptor-associated protein 5, calpain 5, unconventional myosin VIIa, transmembrane protein 126A, coilin 4, cytoplasmic dysin 2 light intermediate chain 1, and 164. kDa centrosome protein, complement C1q tumor necrosis factor-related protein 5, membrane coil-related protein, voltage-dependent calcium channel subunits α-2 / δ-4, guanine nucleotide-binding protein G(I) / G(S) / G(T) subunits β-3, cone rhodopsin-sensitive cGMP 3',5'-cyclic nucleotide phosphodiesterase subunit γ, collagen α-1(II) chain, matrix metalloproteinase 19, retinol dehydrogenase 5, T complex protein 1 subunit β, Baldr-Biedel syndrome-related protein 10, 290 kDa centrosome protein, POC1 centriolein homolog B, mevalonate kinase, flagellated transporter 81 homolog, rescue mitochondrial translational release factor, integrated membrane protein 2B, retinoblastoma-associated protein, protein 1 containing RCC1 and BTB domains, rhodopsin kinase 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 polyglutamyltransferase TTLL5, spermatogenesis 7. Life-related proteins, 8. Triangular tetrapeptide repeat protein, 5. Peronein, 1. Member of the transient receptor potential cation channel subfamily M, 4. γ-tubulin complex component, 1. Sodium / potassium / calcium exchanger, 1. Photoreceptor-specific nuclear receptor, 4. Baldr-Biedel syndrome-related protein, 2. Member of the calcium and integrin binding family, 1. Retinaldehyde binding protein, 1. N-acetylglucosamine-1-phosphotransferase subunit γ, flagellar transporter 140 homolog, 1. Clusterin-related protein, 6. Member of the ATP-binding box subfamily C, 6. Ketoimine reductase μ-crystallin, BatteninZinc finger protein 423, fantom protein, Baldr-Biedel syndrome-associated protein 2, ADP-ribosylation factor-like protein 2 binding protein, cyclic nucleotide-gated cation channel β-1, cadherin 3, pre-mRNA splicing factor ATP-dependent RNA helicase PRP16, platelet-reactive protein motif-containing detegrin and metalloproteinase 18, solute carrier family 38 member 8, retinal guanylate cyclase 1, pre-mRNA processing splicing factor 8, aryl hydrocarbon interacting protein-like 1 protein, membrane-associated phosphatidylinositol transporter 3, unc-119 protein homolog A, possible G protein-coupled receptor 179, Tectonic-like complex member MKS1, carbonic anhydrase 4, G protein signaling regulator 9, arylsulfatase G, pre-mRNA splicing regulator USH1G, photoreceptor disk component PRCD, myofascitis 2, rod rhodopsin-sensitive cGMP 3',5'-cyclic nucleotide phosphodiesterase subunit γ, laminin subunit α-1, AFG3-like protein 2, cone-rod homologous box protein, receptor expression enhancer protein 6, retinal and anterior nerve fold homologous box protein 2, complement C3, Rho guanine nucleotide exchange factor 18, protein containing potato glycoprotein-like phospholipase domain 6, G protein signaling regulator 9 binding protein, optic atrophy protein 3, U4 / U6 small nucleoribonucleoprotein Prp31, mitochondrial isocitrate dehydrogenase [NA] D] Subunit β, mitochondrial pantothenic acid kinase 2, jagged-1 protein, molecular chaperone MKKS, centrosome protein kizuna, lysophosphatidylserine lipase ABHD12, kinin-like protein KIF3B, centrosome-associated protein CEP250, pre-mRNA processing factor 6, ciliary and flagellate-associated protein 410, activator 1-like protein, inhibitor of metalloproteinases 3, flagellated intratransporter 27 homolog, peroneal protein 1, MIEF1 upstream open reading frame protein, mitochondrial aconitine hydratase, γ-tubulin complex component 6, centrioles and centriolear satellite proteins, retinal schistosome protein, XRP2 protein, dystrophin, X-linked retinitis pigmentosa GTPase regulator, night blindness protein, Xaa-Pro dipeptidase, Norrin, voltage-dependent L-type calcium channel subunit α-1F, phosphoglycerate kinase 1, Rab protein geranyl-geranyl transferase component A1, mitochondrial ingress membrane translocase subunit Tim8A, phosphoribosyl pyrophosphate kinase 1. Long-wavelength opsin 1, medium-wavelength opsin 1, short-wavelength opsin 1, mitochondrial transcription factor A, 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 1Cytochrome c oxidase subunit 3, cytochrome b, mitochondrial leucine-tRNA ligase, mitochondrial undifferentiated gamma-glutamyl-tRNA synthetase EARS2, lysine-tRNA ligase, mitochondrial histidine-tRNA ligase, mitochondrial serine-tRNA ligase, mitochondrial proline-tRNA ligase, cyanocobalamin reductase / alkylcoobalamin dealkylase, POU domain class 3 transcription factor 4, ribosomal protein S6 kinase α-6, ciliogenesis and planar cell polar effector 1, Meckelin, TRAF3 interacting protein 1, flagellated transporter 74 homolog, endoplasmic reticulum S-phase cycle protein A-related protein, sodium ion channel and clathrin connector 1, TALPID3 protein, Tectonic-2, ADP ribosylation factor-like protein 13B, B9 domain-containing protein 1, B9 domain-containing protein 2, C2 domain-containing protein 3, 41 kDa centrosomal protein, 104 kDa centrosomal protein, 120 kDa centrosome protein, flagellated transporter 172 homolog, chevone-interacting protein, kinin-like protein KIF7, rod rhodopsin-sensitive cGMP 3',5'-cyclic nucleotide phosphodiesterase subunit δ, Tectonic-1, Tectonic-3, transmembrane protein 107, transmembrane protein 138, transmembrane protein 231, triangular tetrapeptide 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 binding homologous box protein 1, type II keratin Hb3, type I cytoskeleton keratin 12, transforming growth factor β-inducible protein ig-h3, tumor-associated calcium signaling protein 2, carbohydrate sulfonyltransferase 6, gellingin, protein containing UbiA isopentenyltransferase domain 1, core proteoglycan, 1-phosphatidylinositol 3-phosphate 5-kinase, transcription factor Ovo-like 2 protein, granular head-like protein 2 homolog and / or any of its chimeric polypeptides.

[0085] The polynucleotides encoding the polypeptides in this disclosure 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 the following: additional polypeptide tags (e.g., sequences co-framed with the polypeptide to produce a fusion protein), 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 suitable polypeptide tags may include, but are not limited to, any combination of the following: purification tags, such as his tags, flag tags, maltose-binding proteins, and glutathione S-transferase tags; detection tags, such as tags detectable by spectrophotometry (e.g., green fluorescent protein, red fluorescent protein, etc.) and tags with detectable enzyme activity (e.g., alkaline phosphatase, etc.); tags containing secretion sequences, signal sequences, leader sequences, and / or stable sequences; protease cleavage sites (e.g., furin cleavage sites, TEV cleavage sites, thrombin cleavage sites, etc.), etc. In some embodiments, 5' and / or 3' UTRs increase the stability, localization, and / or translation efficiency of polynucleotides. In some embodiments, 5' and / or 3' UTRs improve the level and / or duration of protein expression. In some embodiments, 5' and / or 3' UTRs include elements (e.g., one or more miRNA binding sites, etc.) that can block or reduce off-target expression (e.g., inhibition of expression in specific cell types (e.g., neurons), at specific times in the cell cycle, at specific developmental stages, etc.). In some embodiments, 5' and / or 3' UTRs include elements (e.g., one or more miRNA binding sites, etc.) that can enhance the expression of the encoded polypeptide in specific cell types.

[0086] In some embodiments, the polynucleotide encoding the polypeptide of this disclosure is operatively 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" can include enhancers, insulators, promoters, and other expression control elements (e.g., polyadenylation signals). Any one or more suitable enhancers known in the art can be used, including, for example, enhancer sequences from mammalian genes (such as globin, elastase, albumin, alpha-fetoprotein, insulin, etc.), enhancer sequences from eukaryotic viruses (such as the SV40 enhancer (bp 100-270) posterior to the origin of replication, cytomegalovirus early promoter enhancers, polyomavirus enhancers posterior to the origin of replication, adenovirus enhancers, etc.), and any combination thereof. Any one or more suitable insulators known in the art can be used, including, for example, HSV chromatin boundary (CTRL / CTCF binding / insulator) elements CTRL1 and / or CTRL2, chicken hypersensitive site 4 insulator (cHS4), human HNRPA2B1-CBX3 pervasive chromatin open element (UCOE), scaffold / nuclear matrix attachment region (S / MAR) from human interferon β gene (IFNB1), and any combination thereof. Any suitable promoter known in the art (e.g., suitable for transcription in mammalian host cells) may be used, including promoters derived from the genomes of viruses such as polyomavirus, fowlpox virus, adenovirus (e.g., adenovirus 2), bovine papillomavirus, avian sarcoma virus, cytomegalovirus, retrovirus, hepatitis B virus, simian virus 40 (SV40), etc.; promoters from heterologous mammalian genes (e.g., actin promoters (e.g., β-actin promoters), ubiquitin promoters (e.g., ubiquitin C (UbC) promoters), phosphoglycerate kinase (PGK) promoters, immunoglobulin promoters, heat shock promoters, etc.); promoters from homologous mammalian genes; synthetic promoters (e.g., CAG promoters); and any combination thereof, provided that such promoters are compatible with the host cell. Regulatory sequences may include those that direct constitutive expression of nucleic acids, as well as tissue-specific regulatory sequences and / or inducible or repressive sequences.

[0087] In some embodiments, the polynucleotide of this disclosure is operatively linked to one or more heterologous promoters. In some embodiments, the one or more heterologous promoters are one or more of the following: constitutive promoters, tissue-specific promoters, temporal promoters, spatial promoters, inducible promoters, and repressive promoters. In some embodiments, the one or more heterologous promoters are one or more of the following: human cytomegalovirus (HCMV) immediate 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 polynucleotide encoding the polypeptide of this disclosure is operatively linked to an HCMV promoter.

[0088] In some embodiments, the polynucleotide expressing the polypeptide is achieved when a polynucleotide encoding the polypeptide of this disclosure is delivered to one or more target cells of a subject (e.g., one or more cells of the subject's eye, including the 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, Miller cells, amacrine cells, etc.). In some embodiments, the expression of the polypeptide enhances, increases, enlarges, 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, etc.). In some embodiments, the expression of the polypeptide provides preventive, palliative, 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). Chimeric Peptides

[0089] In some embodiments, the polynucleotide encoding of this disclosure comprises a chimeric polypeptide containing a first polypeptide and a second polypeptide. In some embodiments, the first polypeptide and the second polypeptide are the same. In some embodiments, the first polypeptide and the second polypeptide are different. In some embodiments, the chimeric polypeptide further comprises a linker polypeptide connecting the first polypeptide and the second polypeptide. In some embodiments, the chimeric polypeptide comprises a first polypeptide-linker polypeptide-second polypeptide from the N-terminus to the C-terminus. The first polypeptide and / or the second polypeptide can be any polypeptide described herein or known in the art.

[0090] In some embodiments, the adapter peptide is a cleavable adapter peptide. Any cleavable adapter peptide known in the art can be used in the chimeric peptides of this disclosure, including, for example, T2A adapters, P2A adapters, E2A adapters, and F2A adapters. In some embodiments, the adapter peptide is a T2A adapter peptide. An exemplary nucleic acid sequence encoding a T2A adapter peptide is provided as SEQ ID NO: 1. An exemplary amino acid sequence of a T2A adapter peptide is provided as SEQ ID NO: 5. In some embodiments, the adapter peptide is a P2A adapter peptide. An exemplary nucleic acid sequence encoding a P2A adapter peptide is provided as SEQ ID NO: 2. An exemplary amino acid sequence of a P2A adapter peptide is provided as SEQ ID NO: 6. In some embodiments, the adapter peptide is an E2A adapter peptide. An exemplary nucleic acid sequence encoding an E2A adapter peptide is provided as SEQ ID NO: 3. An exemplary amino acid sequence of an E2A adapter peptide is provided as SEQ ID NO: 7. In some embodiments, the adapter peptide is an F2A adapter peptide. An exemplary nucleic acid sequence encoding the F2A adapter polypeptide is provided as SEQ ID NO: 4. An exemplary amino acid sequence of the F2A adapter polypeptide is provided as SEQ ID NO: 8. In some embodiments, the adapter 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 adapter polypeptide comprises a sequence selected from SEQ ID NO: 5-8.

[0091] In some implementations, the linker peptide is an uncleavable linker peptide. Any non-cleavable linker peptide known in the art can be used in the chimeric peptides of this disclosure, including, for example, the GGGGSGGGGSGGGGS (SEQ ID NO: 9) linker, the GGSSRSSSSGGGGSGGG (SEQ ID NO: 10) linker, the GGGGSGGGGSGGGGSGGGGS (SEQ ID NO: 11) linker, the CGGGSGGGGSGGGGS (SEQ ID NO: 12) linker, the SHGGHGGGGSGGGGS (SEQ ID NO: 13) linker, the MGGMSGGGGSGGGGS (SEQ ID NO: 14) linker, the YGGYSGGGGSGGGGS (SEQ ID NO: 15) linker, the WGGYSGGGGSGGGGS (SEQ ID NO: 16) linker, the SVSVGMKPSPRP (SEQ ID NO: 17) linker, the VISNHAGSSRRL (SEQ ID NO: 18) linker, and the PWIPTPRPTFTG (SEQ ID NO: 19) linker. The adapter peptide includes SEQ ID NO: 19) linker, RGRGRGRGRGR (SEQ ID NO: 20) linker, etc. In some embodiments, the adapter peptide 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 adapter peptide comprises a sequence selected from SEQ ID NO: 9-20.

[0092] In some embodiments, the polynucleotides of this disclosure do not contain the coding sequence of collagen α-1(VII) chain polypeptide (COL7) (e.g., a transgene encoding the aforementioned polypeptide). In some embodiments, the polynucleotides of this disclosure do not contain the coding sequence of lysine hydroxylase 3 polypeptide (LH3) (e.g., a transgene encoding the aforementioned polypeptide). In some embodiments, the polynucleotides of this disclosure do not contain the coding sequence of type I cytoskeleton keratin 17 polypeptide (KRT17) (e.g., a transgene encoding the aforementioned polypeptide). In some embodiments, the polynucleotides of this disclosure do not contain the coding sequence of transglutaminase (TGM) polypeptides (e.g., human transglutaminase polypeptides, such as human TGM1 polypeptide and / or human TGM5 polypeptide) (e.g., a transgene encoding the aforementioned polypeptide). In some embodiments, the polynucleotides of this disclosure do not contain coding sequences for cosmetic proteins (e.g., collagen, fibronectin, elastin, optogenetics, fibronectin / fibronectin receptor, laminin, neuromodulators, fibrils, other dermal extracellular matrix proteins, etc.) (e.g., transgenes encoding the aforementioned proteins). In some embodiments, the polynucleotides of this disclosure do not contain coding sequences for antibodies (e.g., full-length antibodies, antibody fragments, etc.) (e.g., transgenes encoding the aforementioned antibodies). In some embodiments, the polynucleotides of this disclosure do not contain coding sequences for Kazal-type serine protease inhibitor (SPINK) peptides (e.g., human SPINK peptides, such as SPINK5 peptide) (e.g., transgenes encoding the aforementioned peptide). In some embodiments, the polynucleotides of this disclosure do not contain coding sequences for filaggrin or filaggrin 2 peptides (e.g., human filaggrin or filaggrin 2 peptide) (e.g., transgenes encoding the aforementioned peptide). In some embodiments, the polynucleotides in this disclosure do not contain the coding sequence of a cystic fibrosis transmembrane conduction regulator (CFTR) polypeptide (e.g., a human CFTR polypeptide) (e.g., a transgene encoding the aforementioned polypeptide).In some embodiments, the polynucleotides in this disclosure do not contain ichthyosis-related polypeptides (e.g., ATP-binding box 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, corneal chain protein polypeptide, ceramide synthase 3 polypeptide, carbohydrate sulfonyltransferase 8 polypeptide, sealing protein 1 polypeptide, cystatin A polypeptide, cytochrome P4504F22 polypeptide, 3-β-hydroxysteroid-δ(8),δ(7)-isomerase polypeptide, very long chain fatty acid elongation protein 4 polypeptide, filaggrin polypeptide, filaggrin 2 polypeptide, gap junction protein β-2). beta-2 polypeptide, gap junction protein β-3 polypeptide, gap junction protein β-4 polypeptide, gap junction protein β-6 polypeptide, 3-ketodihydrosphingosine reductase polypeptide, type II cytoskeletal keratin 1 polypeptide, type II cytoskeletal 2 epidermal polypeptide, type I cytoskeletal keratin 9 polypeptide, type I cytoskeletal keratin 10 polypeptide, lipase member N polypeptide, clasping protein polypeptide, membrane-bound transcription factor site 2 protease polypeptide, magnesium transporter NIPA4 polypeptide, sterol-4-alpha-carboxylate 3-dehydrogenase (decarboxylase), The coding sequences of the following peptides are provided: decarboxylating peptide, peroxisome guide signal 2 receptor peptide, D-3-phosphoglycerate dehydrogenase peptide, peroxisome phytyl-CoA dioxygenase peptide, potato glycoprotein-like phospholipase domain-containing protein 1 peptide, proteasome mature protein peptide, phosphoserine aminotransferase peptide, short-chain dehydrogenase / reductase family 9C member 7 peptide, serine protease inhibitor B8 peptide, long-chain fatty acid transporter 4 peptide, synaptosome-associated protein 29 peptide, suppressor of tumorigenicity 14 protein peptide, sterol sulfatase peptide, vesicle sorting-associated protein 33B peptide, and CAAX prenyl protease 1 homolog peptide (e.g., transgenes encoding the aforementioned peptides).In some embodiments, the polynucleotides in this disclosure do not contain coding sequences for collagen α-1(VII) chain polypeptide, lysine hydroxylase 3 polypeptide, type I cytoskeleton keratin 17 polypeptide and / or any of its chimeric polypeptides (e.g., transgenes encoding the aforementioned polypeptides).In some embodiments, the polynucleotides in this disclosure do not contain collagen α-1(VII) chain polypeptide, lysine hydroxylase 3 polypeptide, type I cytoskeleton keratin 17 polypeptide, transglutaminase (TGM) polypeptide, filaggrin polypeptide, beauty protein, antibody, SPINK polypeptide, CFTR polypeptide, ichthyosis-related polypeptide, α-1-antitrypsin polypeptide, sodium-dependent phosphotransporter 2B polypeptide, dynein heavy chain 5 axonemal polypeptide, dynein heavy chain 11 polypeptide, protein 39 polypeptide containing coiled-coil domain, dynein intermediate chain 1 polypeptide, protein 40 polypeptide containing coiled-coil domain, protein 103 polypeptide containing coiled-coil domain, sperm-associated antigen 1 polypeptide, protein 10 polypeptide containing zinc finger MYND domain, protein 4 polypeptide containing armadillo repeat sequence, protein 151 polypeptide containing coiled-coil domain, dynein intermediate chain 2 polypeptide, or radial spoke head 1 homolog. Homologous peptides, including protein 114 containing a coiled-coil domain, radiating head protein 4 homolog A peptide, ciliary axis dynein assembly factor 1 peptide, ciliary axis dynein assembly factor 2 peptide, leucine-rich repeat protein 6 peptide, pulmonary surfactant-associated protein B peptide, pulmonary surfactant-associated protein C peptide, Nkx-2.1 homologous box protein, ATP-binding box subfamily A member 3 peptide, cytokine receptor common subunit β peptide, granulocyte-macrophage colony-stimulating factor receptor subunit α peptide, bone morphogenetic protein receptor type 2 peptide, sarcoplasmic reticulum / endoplasmic reticulum calcium ATPase 2 peptide, serine / threonine protein kinase receptor R3 peptide, endothelial glycoprotein (Endoglin) peptide, and mothers against decapentaplegic homolog 9. 9) The coding sequences of the following polypeptides: pituitary protein 1 polypeptide, potassium channel subfamily K member 3 polypeptide, eIF-2-α kinase GCN2 polypeptide, pulmonary surfactant-associated protein A2 polypeptide, telomerase reverse transcriptase polypeptide, dyskeratin polypeptide, regulator of telomere elongation helicase 1 polypeptide, poly(A)-specific ribonuclease PARN polypeptide, TERF1 interacting nuclear factor 2 polypeptide, H / ACA ribonucleoprotein complex non-core subunit NAF1 polypeptide, mucin 5B polypeptide, desmosome plaque polypeptide, CST complex subunit STN1 polypeptide, dipeptidyl peptidase 9 polypeptide, and / or any of their chimeric polypeptides (e.g., transgenes encoding the aforementioned substances).

[0093] In some embodiments, the polynucleotides of this disclosure do not contain coding sequences for immunomodulatory peptides (e.g., transgenes encoding the aforementioned peptides). In some embodiments, the polynucleotides of this disclosure do not contain coding sequences for cytokine peptides and / or chemokine peptides (e.g., transgenes encoding the aforementioned peptides). In some embodiments, the polynucleotides of this disclosure do not contain coding sequences for cytokine peptides (e.g., transgenes encoding the aforementioned peptides). In some embodiments, the polynucleotides of this disclosure do not contain coding sequences for IL-1 peptide, IL-2 peptide, IL-7 peptide, IL-12 peptide, IL-13 peptide, IL-15 peptide, IL-17 peptide, IL-18 peptide, IL-28 peptide, IL-32 peptide, IL-33 peptide, IL-34 peptide, TNFα peptide, IFNγ peptide, G-CSF peptide, GM-CSF peptide, and / or any chimeric peptide thereof (e.g., transgenes encoding the aforementioned peptides).

[0094] In some embodiments, the polynucleotides of this disclosure do not contain the coding sequence of chemokine polypeptides (e.g., transgenes encoding the aforementioned polypeptides). In some embodiments, the polynucleotides of this disclosure do not contain the coding sequence of 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 the aforementioned polypeptides). Recombinant nucleic acid

[0095] In some embodiments, this disclosure relates to recombinant nucleic acids comprising any one or more 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, vectors suitable for maintaining, propagating, and / or expressing polynucleotides in a subject to produce one or more polypeptides can be used. Examples of suitable vectors may include, for example, plasmids, granules, episomes, transposons, and viral vectors (e.g., adenovirus vectors, adeno-associated virus vectors, vaccinia virus vectors, Sindbis virus vectors, measles virus 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 a host cell. In some embodiments, the vector is not capable of autonomous replication in a host cell. In some embodiments, the vector can integrate into the host DNA. In some embodiments, the vector cannot integrate into the host DNA (e.g., it is free). Methods for preparing vectors containing one or more target polynucleotides are well known to those skilled in the art and include, for example, chemical synthesis or artificial manipulation of isolated segments of nucleic acids (e.g., through genetic engineering techniques).

[0096] In some embodiments, the recombinant nucleic acid of this disclosure is a herpes simplex virus (HSV) amplicon. Herpes simplex virus amplicon (including its structural characteristics and preparation methods) are generally known to those skilled in the art (see, for example, deSilva 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 heterozygous amplicon. Examples of HSV-1 heterozygous amplicon may include, but are not limited to, HSV / AAV heterozygous amplicon, HSV / EBV heterozygous amplicon, HSV / EBV / RV heterozygous amplicon, and / or HSV / Sleeping Beauty heterozygous amplicon. In some embodiments, the amplicon is an HSV / AAV heterozygous amplicon. In some embodiments, the amplicon is an HSV / Sleeping Beauty heterozygous amplicon.

[0097] In some embodiments, the recombinant nucleic acid of this disclosure is a recombinant herpesvirus genome. The recombinant herpesvirus genome can be a recombinant genome from any member of the Herpesviridae family of DNA viruses known in the art, including, for example, 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 EBV genome, recombinant Kaposi's sarcoma-associated herpesvirus genome, and any combination or derivative thereof. In some embodiments, the recombinant herpesvirus 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. As used herein, "inactivating mutation" can refer to any mutation that results in a reduced, undetectable, or eliminated amount and / or function of a gene or regulatory 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 the transcriptional control sequences (promoters, enhancers, insulators, etc.) and / or coding sequences of a given gene or regulator. Any suitable method known in the art for measuring the amount of gene or regulator product can be used, including, for example, qPCR, RNA blotting, RNAseq, 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 replicative. In some embodiments, the recombinant herpesvirus genome is replication-deficient. In some embodiments, the recombinant herpesvirus genome is not oncolytic.

[0098] In some embodiments, the recombinant nucleic acid is a recombinant herpes simplex virus (HSV) genome. In some embodiments, the recombinant HSV 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 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 HSV genome is attenuated (e.g., compared to the corresponding wild-type herpes simplex virus genome). In some embodiments, the recombinant HSV genome is replicative. In some embodiments, the recombinant HSV genome is replication-deficient. In some embodiments, the recombinant HSV genome is not oncolytic.

[0099] 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 can be derived from any HSV-1 strain known in the art, including, for example, strains 17, Ty25, R62, S25, Ku86, S23, R11, Ty148, Ku47, and 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- 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, etc. (see, for example, Bowen et al. J Virol. 2019 April 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, the recombinant HSV-1 genome is attenuated (e.g., compared to the corresponding wild-type HSV-1 genome). In some implementations, the recombinant HSV-1 genome is replicative. In some implementations, the recombinant HSV-1 genome is replication-deficient. In some implementations, the recombinant HSV-1 genome is not oncolytic.

[0100] In some embodiments, the recombinant herpes simplex virus genome includes 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: Infected 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 include inactivating mutations in the ICP34.5 (one or two copies) and / or ICP47 herpes simplex virus genes (e.g., to avoid generating immune-stimulating viruses). In some embodiments, the recombinant herpes simplex virus genome does not include inactivating mutations in the ICP34.5 (one or two copies) herpes simplex virus gene. In some embodiments, the recombinant herpes simplex virus genome does not include inactivating mutations in the 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 two 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 does not have conditional replication capability. In some embodiments, the recombinant herpes simplex virus genome does not have conditional replication capability in cancer cells.

[0101] In some embodiments, the recombinant herpes simplex virus genome contains an inactivating mutation in the ICP0 gene (one or two copies). In some embodiments, the recombinant herpes simplex virus genome contains an inactivating mutation in the ICP0 gene (one or two copies), and further contains inactivating mutations in the ICP4 (one or two copies), ICP22, ICP27, ICP47, UL41, and / or UL55 genes. In some embodiments, the recombinant herpes simplex virus genome contains an inactivating mutation in both the ICP0 and ICP4 genes. In some embodiments, the recombinant herpes simplex virus genome contains an inactivating mutation in both the ICP0 and ICP22 genes. In some embodiments, the recombinant herpes simplex virus genome contains an inactivating mutation in both the ICP0 and UL41 genes. In some embodiments, the recombinant herpes simplex virus genome includes inactivating mutations in the ICP0 gene (one or two copies), the ICP4 gene (one or two copies), and the ICP22 gene. In some embodiments, the recombinant herpes simplex virus genome includes inactivating mutations in the ICP0 gene (one or two copies), the ICP4 gene (one or two copies), and the UL41 gene. In some embodiments, the recombinant herpes simplex virus genome includes inactivating mutations in the ICP0 gene (one or two copies), the ICP22 gene, and the UL41 gene. In some embodiments, the recombinant herpes simplex virus genome includes inactivating mutations in the ICP0 gene (one or two copies), the ICP4 gene (one or two copies), the ICP22 gene, and the UL41 gene. In some embodiments, the inactivating mutation is a deletion of the coding sequences of the ICP0 (one or two copies), ICP4 (one or two copies), ICP22, and / or UL41 genes. In some embodiments, the recombinant herpes simplex virus genome further includes inactivating mutations in the ICP27, ICP47, and / or UL55 genes.

[0102] In some embodiments, the recombinant herpes simplex virus genome contains an inactivating mutation in the ICP4 gene (one or two copies). In some embodiments, the recombinant herpes simplex virus genome contains an inactivating mutation in the ICP4 gene (one or two copies), and further contains inactivating mutations in the ICP0 (one or two copies), ICP22, ICP27, ICP47, UL41, and / or UL55 genes. In some embodiments, the recombinant herpes simplex virus genome contains an inactivating mutation in the ICP4 gene (one or two copies) and an inactivating mutation in the ICP22 gene. In some embodiments, the recombinant herpes simplex virus genome contains an inactivating mutation in the ICP4 gene (one or two copies) and an inactivating mutation in the UL41 gene. In some embodiments, the recombinant herpes simplex virus genome contains an inactivating mutation in the ICP4 gene (one or two copies), 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 of the ICP4 (one or two copies), ICP22, and / or UL41 genes. In some embodiments, the recombinant herpes simplex virus genome further includes inactivating mutations in the ICP0 (one or two copies), ICP27, ICP47, and / or UL55 genes.

[0103] In some embodiments, the recombinant herpes simplex virus genome includes an inactivating mutation in the ICP22 gene. In some embodiments, the recombinant herpes simplex virus genome includes an inactivating mutation in the ICP22 gene and further includes inactivating mutations in the ICP0 (one or two copies), ICP4 (one or two copies), ICP27, ICP47, UL41, and / or UL55 genes. In some embodiments, the recombinant herpes simplex virus genome includes 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 of the ICP22 and / or UL41 genes. In some embodiments, the recombinant herpes simplex virus genome further includes inactivating mutations in the ICP0 (one or two copies), ICP4 (one or two copies), ICP27, ICP47, and / or UL55 genes.

[0104] In some embodiments, the recombinant herpes simplex virus genome includes an inactivating mutation in the ICP27 gene. In some embodiments, the recombinant herpes simplex virus genome includes an inactivating mutation in the ICP27 gene, and further includes inactivating mutations in the ICP0 (one or two copies), ICP4 (one or two copies), ICP22, ICP47, UL41, and / or UL55 genes. In some embodiments, the inactivating mutation is a deletion of the coding sequence of the ICP27 gene.

[0105] In some embodiments, the recombinant herpes simplex virus genome includes an inactivating mutation in the ICP47 gene. In some embodiments, the recombinant herpes simplex virus genome includes an inactivating mutation in the ICP47 gene, and further includes inactivating mutations in the ICP0 (one or two copies), ICP4 (one or two copies), ICP22, ICP27, UL41, and / or UL55 genes. In some embodiments, the inactivating mutation is a deletion of the coding sequence of the ICP47 gene.

[0106] In some embodiments, the recombinant herpes simplex virus genome includes an inactivating mutation in the UL41 gene. In some embodiments, the recombinant herpes simplex virus genome includes an inactivating mutation in the UL41 gene and further includes inactivating mutations in the ICP0 (one or two copies), ICP4 (one or two copies), ICP22, ICP27, ICP47, and / or UL55 genes. In some embodiments, the inactivating mutation is a deletion of the coding sequence of the UL41 gene.

[0107] In some embodiments, the recombinant herpes simplex virus genome includes an inactivating mutation in the UL55 gene. In some embodiments, the recombinant herpes simplex virus genome includes an inactivating mutation in the UL55 gene and further includes inactivating mutations in the ICP0 (one or two copies), ICP4 (one or two copies), ICP22, ICP27, ICP47, and / or UL41 genes. In some embodiments, the inactivating mutation is a deletion of the coding sequence of the UL55 gene.

[0108] In some embodiments, the recombinant herpes simplex virus genome includes inactivating mutations (e.g., deletions of the region) in internal repeat (joint) regions, which include internal repeat long (IR) regions. L ) and internal repeat short (IR) regions SIn some embodiments, inactivation (e.g., deletion) of the conjugate region eliminates one copy each of the ICP4 and ICP0 genes. In some embodiments, inactivation (e.g., deletion) of the conjugate region further inactivates (e.g., deletion) the promoters of the ICP22 and ICP47 genes. If desired, expression of one or both of these genes can be restored by inserting an immediate early promoter into the recombinant herpes simplex virus genome (see, for example, Hill et al. (1995). Nature 375(6530): 411-415; Goldsmith et al. (1998). J Exp Med 187(3): 341-348). It is not intended to be theoretically rigorous, but it is thought that inactivation (e.g., deletion) of the conjugate 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.

[0109] In some embodiments, the recombinant herpes simplex virus genome contains inactivating mutations in the ICP4 (one or two copies), ICP22, and ICP27 genes. In some embodiments, the recombinant herpes simplex virus genome contains inactivating mutations in the ICP4 (one or two copies), ICP27, and UL55 genes. In some embodiments, the inactivating mutations in the ICP4 (one or two copies), ICP27, and / or UL55 genes are deletions of the coding sequences of the ICP4 (one or two copies), ICP27, and / or UL55 genes. In some embodiments, the inactivating mutations in the ICP22 and ICP47 genes are deletions in the promoter regions of the ICP22 and ICP47 genes (e.g., the coding sequences of ICP22 and ICP47 are intact but lack transcriptional activity). In some embodiments, the recombinant herpes simplex virus genome includes deletions in the coding sequences of the ICP4 (one or two copies), ICP27, and UL55 genes, as well as deletions in the promoter regions of the ICP22 and ICP47 genes. In some embodiments, the recombinant herpes simplex virus genome further includes inactivating mutations in the ICP0 (one or two copies) and / or UL41 genes.

[0110] In some embodiments, the recombinant herpes simplex virus genome contains inactivating mutations in the ICP0 gene (one or two copies). In some embodiments, the recombinant herpes simplex virus genome contains inactivating mutations in the ICP0 gene (one or two copies) and the ICP4 gene (one or two copies). In some embodiments, the recombinant herpes simplex virus genome contains inactivating mutations in the ICP0 (one or two copies), ICP4 (one or two copies), and ICP22 genes. In some embodiments, the recombinant herpes simplex virus genome contains inactivating mutations in the ICP0 (one or two copies), ICP4 (one or two copies), ICP22, ICP27, and UL55 genes. In some embodiments, inactivating mutations in the ICP0 (one or two copies), ICP4 (one or two copies), ICP22, ICP27, and / or UL55 genes include deletions of the coding sequences of the ICP0 (one or two copies), ICP4 (one or two 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.

[0111] In some embodiments, the recombinant herpes simplex virus genome comprises one or more polynucleotides of the present disclosure within one, two, three, four, five, six, seven, or more viral loci. Examples of suitable viral loci may include, but are not limited to, ICP0 (one or two copies), ICP4 (one or two copies), ICP22, ICP27, ICP47, tk, UL41, and UL55 herpes simplex virus loci. In some embodiments, the recombinant herpes simplex virus genome comprises one or more polynucleotides of the present disclosure within one or two viral ICP4 loci (e.g., the recombinant virus comprises one or two polynucleotides encoding a polypeptide at the ICP4 locus). In some embodiments, the recombinant herpes simplex virus genome comprises one or more polynucleotides of the present disclosure within the viral ICP22 locus (e.g., the recombinant virus comprises a polynucleotide encoding a polypeptide at the ICP22 locus). In some embodiments, the recombinant herpes simplex virus genome comprises one or more polynucleotides of the present disclosure within the viral UL41 locus (e.g., the recombinant virus comprises a polynucleotide encoding a polypeptide at the UL41 locus). In some embodiments, the recombinant herpes simplex virus genome contains one or more polynucleotides of the present disclosure within the viral ICP27 locus (e.g., the recombinant virus contains a polynucleotide encoding a polypeptide at the ICP27 locus). In some embodiments, the recombinant herpes simplex virus genome contains one or more polynucleotides of the present disclosure within the viral ICP47 locus (e.g., the recombinant virus contains a polynucleotide encoding a polypeptide at the ICP47 locus). In some embodiments, the recombinant herpes simplex virus genome contains one or more polynucleotides of the present disclosure within the viral UL55 locus (e.g., the recombinant virus contains a polynucleotide encoding a polypeptide at the UL55 locus). In some embodiments, the recombinant herpes simplex virus genome contains one or more polynucleotides of the present disclosure within the viral tk locus (e.g., the recombinant virus contains a polynucleotide encoding a polypeptide at the tk locus).

[0112] In some embodiments, the recombinant herpes simplex virus genome comprises one or more polynucleotides of the present disclosure within one or two viral ICP4 loci, and one or more polynucleotides of the present disclosure within the viral ICP22 locus (e.g., the recombinant virus comprises one or two polynucleotides encoding a polypeptide at one or two ICP4 loci, and a polynucleotide encoding a polypeptide at the ICP22 locus). In some embodiments, the recombinant herpes simplex virus genome comprises one or more polynucleotides of the present disclosure within one or two viral ICP4 loci, and one or more polynucleotides of the present disclosure within the viral UL41 locus (e.g., the recombinant virus comprises one or two polynucleotides encoding a polypeptide at one or two ICP4 loci, and a polynucleotide encoding a polypeptide at the UL41 locus). In some embodiments, the recombinant herpes simplex virus genome comprises one or more polynucleotides of the present disclosure within the viral ICP22 locus, and one or more polynucleotides of the present disclosure within the viral UL41 locus (e.g., the recombinant virus comprises a polynucleotide encoding a polypeptide at the ICP22 locus, and a polynucleotide encoding a polypeptide at the UL41 locus). In some embodiments, the recombinant herpes simplex virus genome comprises one or more polynucleotides of the present disclosure within one or two viral ICP4 loci, one or more polynucleotides of the present disclosure within the viral ICP22 locus, and one or more polynucleotides of the present disclosure within the viral UL41 locus (e.g., the recombinant virus comprises one or two polynucleotides encoding a polypeptide at one or two ICP4 loci, a polynucleotide encoding a polypeptide at the ICP22 locus, and a polynucleotide encoding a polypeptide at the UL41 locus). In some embodiments, the recombinant herpes simplex virus genome comprises one or more polynucleotides of the present disclosure within one or two viral ICP4 loci, one or more polynucleotides of the present disclosure within the viral ICP22 locus, one or more polynucleotides of the present disclosure within the viral UL41 locus, one or more polynucleotides of the present disclosure within the viral ICP27 locus, one or more polynucleotides of the present disclosure within the viral ICP47 locus, one or more polynucleotides of the present disclosure within the viral tk locus, and / or one or more polynucleotides of the present disclosure within the viral UL55 locus.

[0113] In some embodiments, the recombinant herpesvirus genome (e.g., the recombinant herpes simplex virus genome) has been 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 two copies of the HSV ICP0 gene, one or two 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, the recombinant herpesvirus genome (e.g., the recombinant herpes simplex virus genome) has been 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., the 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 cells of the eye (primary cells or cell lines derived therefrom). In some embodiments, the cytotoxicity (e.g., in target cells) of the 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 the recombinant ΔICP4 (one or two copies) herpes simplex virus genome in target cells compared to the wild-type herpes simplex virus genome; measuring the relative cytotoxicity of the recombinant ΔICP4 (one or two copies) / ΔICP22 herpes simplex virus genome in target cells compared to the wild-type herpes simplex virus genome, etc.).In some embodiments, the cytotoxicity (e.g., in target cells) of the recombinant herpesvirus genome (e.g., recombinant herpes simplex virus genome) is reduced by at least about 1.5-fold, at least about 2-fold, at least about 3-fold, at least about 4-fold, at least about 5-fold, at least about 6-fold, at least about 7-fold, at least about 8-fold, at least about 9-fold, at least about 10-fold, at least about 15-fold, at least about 20-fold, at least about 25-fold, at least about 50-fold, at least about 75-fold, at least about 100-fold, at least about 250-fold, at least about 500-fold, at least about 750-fold, at least about 1000-fold, or more-fold compared to the wild-type herpes simplex virus genome (e.g., measuring the relative cytotoxicity of the recombinant ΔICP4 (one or two copies) herpes simplex virus genome in target cells compared to the wild-type herpes simplex virus genome; measuring the relative cytotoxicity of the recombinant ΔICP4 (one or two copies) / ΔICP22 herpes simplex virus genome in target cells compared to the wild-type herpes simplex virus genome, etc.). Methods for measuring cytotoxicity are known to those skilled in the art, including, for example, the use of live dyes (formazan dyes), protease biomarkers, MTT assays (or assays using relevant tetrazolium salts (such as XTT, MTS, water-soluble tetrazolium salts, etc.)), and the measurement of ATP content.

[0114] In some embodiments, the recombinant genome (e.g., recombinant herpes simplex virus genome) has been engineered to reduce its effect on target cell proliferation after target cells are exposed 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 cells of the eye (primary cells or cell lines derived therefrom). In some embodiments, target cells exposed to the recombinant genome proliferate 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 cells exposed to the wild-type herpes simplex virus genome (e.g., relative cell proliferation after exposure to the recombinant ΔICP4 (one or two copies) herpes simplex virus genome, measured in target cells compared to cell proliferation after exposure to the wild-type herpes simplex virus genome; relative cell proliferation after exposure to the recombinant ΔICP4 (one or two copies) / ΔICP22 herpes simplex virus genome, etc., measured in target cells compared to cell proliferation after exposure to the wild-type herpes simplex virus genome). In some embodiments, target cell proliferation after exposure to the 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 than target cell proliferation after exposure to the wild-type herpes simplex virus genome (e.g., relative cell proliferation after exposure to the recombinant ΔICP4 (one or two copies) herpes simplex virus genome, measured in target cells; relative cell proliferation after exposure to the recombinant ΔICP4 (one or two copies) / ΔICP22 herpes simplex virus genome, measured in target cells, compared to cell proliferation after exposure to the wild-type herpes simplex virus genome). Methods for measuring cell proliferation are known to those skilled in the art, including, for example, the use of Ki67 cell proliferation assays, BrdU cell proliferation assays, etc.

[0115] The vector (e.g., a herpesvirus vector) may contain one or more polynucleotides of the present disclosure in a form suitable for expression in a host cell. The vector may contain one or more regulatory sequences (e.g., as described above) operatively linked to the polynucleotide to be expressed.

[0116] In some implementations, this disclosure relates to one or more heteropolynucleotides (e.g., bacterial artificial chromosomes (BACs)) comprising any recombinant nucleic acid described herein.

[0117] In some embodiments, the recombinant nucleic acid (e.g., a recombinant herpes simplex virus genome) of this disclosure contains one or more polynucleotides described herein inserted into the recombinant nucleic acid in any orientation. If the recombinant nucleic acid contains two or more polynucleotides described herein (e.g., two or more, three or more, etc.), the polynucleotides may be inserted in the same or opposite orientations. Not wishing to be bound by theory, incorporating two polynucleotides (e.g., two transgenes) in an antisense orientation into the recombinant nucleic acid (e.g., a vector) can help avoid read-throughs and ensure proper expression of each polynucleotide.

[0118] In some embodiments, the recombinant nucleic acid of this disclosure does not contain a polynucleotide encoding a collagen α-1(VII) chain polypeptide (COL7). In some embodiments, the recombinant nucleic acid of this disclosure does not contain a polynucleotide encoding a lysine hydroxylase 3 polypeptide (LH3). In some embodiments, the recombinant nucleic acid of this disclosure does not contain a polynucleotide encoding a type I cytoskeleton keratin 17 polypeptide (KRT17). In some embodiments, the recombinant nucleic acid of this disclosure does not contain a polynucleotide encoding a transglutaminase (TGM) polypeptide (e.g., human transglutaminase polypeptides, such as human TGM1 polypeptide and / or human TGM5 polypeptide). In some embodiments, the recombinant nucleic acid of this disclosure does not contain a polynucleotide encoding cosmetic proteins (e.g., collagen, fibronectin, elastin, optogenetics, fibronectin / fibronectin receptor, laminin, neuromodulators, fibrils, other dermal extracellular matrix proteins, etc.). In some embodiments, the recombinant nucleic acid of this disclosure does not contain a polynucleotide encoding an antibody (e.g., a full-length antibody, an antibody fragment, etc.). In some embodiments, the recombinant nucleic acid of this disclosure does not contain a polynucleotide encoding a Kazal-type serine protease inhibitor (SPINK) polypeptide (e.g., a human SPINK polypeptide, such as SPINK5 polypeptide). In some embodiments, the recombinant nucleic acid of this disclosure does not contain a polynucleotide encoding filaggrin or filaggrin 2 polypeptide (e.g., human filaggrin or filaggrin 2 polypeptide). In some embodiments, the recombinant nucleic acid of this disclosure does not contain a polynucleotide encoding a cystic fibrosis transmembrane conduction regulator (CFTR) polypeptide (e.g., a human CFTR polypeptide).In some embodiments, the recombinant nucleic acid of this disclosure does not contain polypeptides encoding ichthyosis-related peptides (e.g., ATP-binding box 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, hydroperoxidase ALOXE3 polypeptide, AP-1 complex subunit σ-1A polypeptide, arylsulfatase E polypeptide, caspase 14 polypeptide, corneal chain protein polypeptide, ceramide synthase 3 polypeptide, carbohydrate sulfotransferase 8 polypeptide, sealing protein 1 polypeptide, cystatin A polypeptide, cytochrome P450). 4F22 polypeptide, 3-β-hydroxysteroid-δ(8),δ(7)-isomerase polypeptide, very long chain fatty acid elongation protein 4 polypeptide, filaggrin polypeptide, filaggrin 2 polypeptide, gap connexin β-2 polypeptide, gap connexin β-3 polypeptide, gap connexin β-4 polypeptide, gap connexin β-6 polypeptide, 3-ketodihydrosphingosine reductase polypeptide, type II cytoskeletal keratin 1 polypeptide, epidermal type II cytoskeletal keratin 2 polypeptide, type I cytoskeletal keratin 9 polypeptide, type I cytoskeletal keratin 10 polypeptide, lipase member N polypeptide, smear protein polypeptide, membrane-bound transcription factor site 2 protease polypeptide, magnesium transporter NIPA4 polypeptide, sterol-4 The following polynucleotides are included: α-carboxylic acid 3-dehydrogenase (decarboxylation) polypeptide, peroxisome guide signal 2 receptor polypeptide, D-3-phosphoglycerate dehydrogenase polypeptide, peroxisome phytyl-CoA dioxygenase polypeptide, protein 1 containing potato glycoprotein-like phospholipase domain, proteasome maturation protein polypeptide, phosphoserine aminotransferase polypeptide, short-chain dehydrogenase / reductase family 9C member 7 polypeptide, serine protease inhibitor B8 polypeptide, long-chain fatty acid transporter 4 polypeptide, synaptosome-associated protein 29 polypeptide, tumorigenic inhibitor 14 protein polypeptide, sterol sulfatase polypeptide, vesicle sorting protein-associated protein 33B polypeptide, and CAAX isopentenyl protease 1 homolog polypeptide. In some embodiments, the recombinant nucleic acids of this disclosure do not contain polynucleotides encoding collagen α-1(VII) chain polypeptide, lysine hydroxylase 3 polypeptide, type I cytoskeleton keratin 17 polypeptide, and / or any of their chimeric polypeptides.In some embodiments, the recombinant nucleic acid of this disclosure does not contain the following peptides: collagen α-1(VII) chain polypeptide, lysine hydroxylase 3 polypeptide, type I cytoskeleton keratin 17 polypeptide, transglutaminase (TGM) polypeptide, filaggrin polypeptide, beauty protein, antibody, SPINK polypeptide, CFTR polypeptide, ichthyosis-related polypeptide, α-1-antitrypsin polypeptide, sodium-dependent phosphotransporter 2B polypeptide, ciliary axis dynein heavy chain 5 polypeptide, ciliary axis dynein heavy chain 11 polypeptide, protein 39 polypeptide containing coiled-coil domain, and ciliary axis dynein heavy chain 5 polypeptide. Powerin intermediate chain 1 polypeptide, protein 40 containing coiled-coil domain polypeptide, protein 103 containing coiled-coil domain polypeptide, sperm-associated antigen 1 polypeptide, protein 10 containing zinc finger MYND domain polypeptide, protein 4 containing armadillo repeat sequence polypeptide, protein 151 containing coiled-coil domain polypeptide, ciliary axis dynein intermediate chain 2 polypeptide, radial head protein 1 homolog polypeptide, protein 114 containing coiled-coil domain polypeptide, radial head protein 4 homolog A polypeptide, ciliary axis dynein assembly factor 1 polypeptide, ciliary axis dynein assembly factor 2 polypeptide, containing leucine-rich polypeptide Acid repeat sequence protein 6 polypeptide, pulmonary surfactant-associated protein B polypeptide, pulmonary surfactant-associated protein C polypeptide, homeobox protein Nkx-2.1 polypeptide, ATP binding box subfamily A member 3 polypeptide, cytokine receptor common subunit β polypeptide, granulocyte-macrophage colony-stimulating factor receptor subunit α polypeptide, bone morphogenetic protein receptor type 2 polypeptide, sarcoplasmic reticulum / endoplasmic reticulum calcium ATPase 2 polypeptide, serine / threonine protein kinase receptor R3 polypeptide, endothelial glycoprotein polypeptide, maternal anti-Dpp homolog 9 polypeptide, pituitary protein 1 polypeptide, potassium ion channel subunit The polynucleotides of family K member 3 peptide, eIF-2-α kinase GCN2 peptide, pulmonary surfactant-associated protein A2 peptide, telomerase reverse transcriptase peptide, dyskeratin protein peptide, telomere elongation helicase regulator 1 peptide, poly(A)-specific ribonuclease PARN peptide, TERF1 interacting nuclear factor 2 peptide, H / ACA ribonucleoprotein complex non-core subunit NAF1 peptide, mucin 5B peptide, desmosome plaque protein peptide, CST complex subunit STN1 peptide, dipeptidyl peptidase 9 peptide and / or any of its chimeric peptides.

[0119] In some embodiments, the recombinant nucleic acid of this disclosure does not contain a polynucleotide encoding an immunomodulatory polypeptide. In some embodiments, the recombinant nucleic acid of this disclosure does not contain a polynucleotide encoding a cytokine polypeptide and / or a chemokine polypeptide. In some embodiments, the recombinant nucleic acid of this disclosure does not contain a polynucleotide encoding a cytokine polypeptide. In some embodiments, the recombinant nucleic acid of this disclosure does not contain a polynucleotide 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.

[0120] In some embodiments, the recombinant nucleic acid of this disclosure does not contain a polynucleotide encoding a chemokine polypeptide. In some embodiments, the recombinant nucleic acid of this disclosure does not contain a polynucleotide encoding a CXCL1 polypeptide, a CXCL2 polypeptide, a CXCL8 polypeptide, a CXCL9 polypeptide, a CXCL11 polypeptide, a CXCL16 polypeptide, a CCL2 polypeptide, a CCL3 polypeptide, a CCL4 polypeptide, a CCL5 polypeptide, a CCL11 polypeptide, and / or any chimeric polypeptide thereof. IV. Virus

[0121] 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., a human). In some embodiments, the virus is adapted to deliver polynucleotides and / or recombinant nucleic acids to one or more target cells of a subject (e.g., a human). In some embodiments, one or more target cells are human cells. In some embodiments, 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; Miller cells; amacrine cells, etc.).

[0122] Any suitable virus known in the art can be used, including, for example, adenovirus, adeno-associated virus, retrovirus, lentivirus, Sendai virus, papillomavirus, herpesvirus (e.g., herpes simplex virus), vaccinia virus, and / or any hybrid or derived virus thereof. In some embodiments, the virus is attenuated. In some embodiments, the virus is capable of replication. In some embodiments, the virus is replication-defective. In some embodiments, the virus is not oncolytic. In some embodiments, the virus has been modified to alter its tissue tropism relative 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 generating viruses comprising recombinant nucleic acids are well known to those skilled in the art.

[0123] In some embodiments, the virus is a member of the DNA virus herpesviridae family, including, for example, herpes simplex virus, varicella-zoster virus, human cytomegalovirus, herpesvirus 6A, herpesvirus 6B, herpesvirus 7, Epstein-Barr virus (EBV), and Kaposi's sarcoma-associated herpesvirus. In some embodiments, the herpesvirus is attenuated. In some embodiments, the herpesvirus is replication-defective. In some embodiments, the herpesvirus is capable of replication. In some embodiments, the herpesvirus has been 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 exhibits reduced cytotoxicity compared to the corresponding wild-type herpesvirus. In some embodiments, the herpesvirus is not oncolytic.

[0124] In some embodiments, the virus is herpes simplex virus (HSV). HSV containing recombinant nucleic acid can be generated by methods disclosed, for example, in WO 2015 / 009952, WO 2017 / 176336, WO 2019 / 200163 and / or WO 2019 / 210219. In some embodiments, the HSV is attenuated. In some embodiments, the HSV is replication-defective. In some embodiments, the HSV is replicative. In some embodiments, the HSV has been engineered to reduce or eliminate the expression of one or more HSV genes (e.g., one or more virulent HSV genes). In some embodiments, the HSV has reduced cytotoxicity compared to the corresponding wild-type HSV. In some embodiments, the HSV is not oncolytic. In some embodiments, the HSV is HSV-1, HSV-2, or any derivative thereof. In some embodiments, the HSV is HSV-1. In some embodiments, HSV-1 is attenuated. In some embodiments, HSV-1 is replication-deficient. In some embodiments, HSV-1 is capable of replication. In some embodiments, HSV-1 has been 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 exhibits reduced cytotoxicity compared to the corresponding wild-type HSV-1. In some embodiments, HSV-1 is not oncolytic.

[0125] In some embodiments, the herpes simplex virus has been modified to alter its tissue tropism relative to that of the unmodified wild-type herpes simplex virus. In some embodiments, the herpes simplex virus comprises a modified envelope. In some embodiments, the modified envelope comprises one or more (e.g., one or more, two or more, three or more, four or more, etc.) mutant 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 tissue tropism of the herpes simplex virus relative to the wild-type herpes simplex virus.

[0126] In some embodiments, the transduction efficiency (in vitro and / or in vivo) of the virus of this 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 from 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 viral transduction efficiency in vitro or in vivo are well known to those skilled in the art, including, for example, qPCR analysis, deep sequencing, Western blotting, fluorescence analysis (such as fluorescence in situ hybridization (FISH), fluorescent reporter gene expression, immunofluorescence, FACS), etc.

[0127] In some embodiments, this document provides a recombinant virus, which may or may not be a pseudotype, that produces one or more therapeutic peptides for treating an eye condition or disease. In some embodiments, one or more therapeutic peptides produced by the recombinant virus described herein mediate or enhance the treatment of the eye condition or disease. This disclosure further provides therapeutic compositions comprising a recombinant virus and methods for treating an eye condition or disease. V. Pharmaceutical compositions and formulations

[0128] Certain aspects of this 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 containing recombinant genomes) described herein (such as herpes simplex virus containing recombinant herpes simplex virus genomes) as well as pharmaceutically acceptable excipients or vectors.

[0129] In some embodiments, the pharmaceutical composition or preparation comprises any one or more viruses described herein (e.g., herpesviruses). In some embodiments, the pharmaceutical composition or preparation comprises from about 104 To about 10 12 Plaque-forming units (PFU) / mL of virus. For example, a pharmaceutical composition or formulation may contain from about 10 4 To about 10 12 Approximately 10 5 To about 10 12 Approximately 10 6 To about 10 12 Approximately 10 7 To about 10 12 Approximately 10 8 To about 10 12 Approximately 10 9 To about 10 12 Approximately 10 10 To about 10 12 Approximately 10 11 To about 10 12 Approximately 10 4 To about 10 11 Approximately 10 5 To about 10 11 Approximately 10 6 To about 10 11 Approximately 10 7 To about 10 11 Approximately 10 8 To about 10 11 Approximately 10 9 To about 10 11 Approximately 10 10 To about 10 11 Approximately 10 4 To about 10 10 Approximately 10 5 To about 10 10 Approximately 10 6 To about 10 10 Approximately 10 7 To about 10 10 Approximately 10 8 To about 10 10 Approximately 10 9 To about 10 10 Approximately 10 4 To about 10 9 Approximately 10 5 To about 10 9 Approximately 10 6 To about 10 9 Approximately 10 7 To about 10 9 Approximately 10 8 To about 10 9 Approximately 10 4 To about 10 8 Approximately 10 5 To about 108 Approximately 10 6 To about 10 8 Approximately 10 7 To about 10 8 Approximately 10 4 To about 10 7 Approximately 10 5 To about 10 7 Approximately 10 6 To about 10 7 Approximately 10 4 To about 10 6 Approximately 10 5 To about 10 6 Or about 10 4 To about 10 5 The virus is present at PFU / mL. In some embodiments, the pharmaceutical composition or formulation contains about 10 PFU / mL. 4 Approximately 10 5 Approximately 10 6 Approximately 10 7 Approximately 10 8 Approximately 10 9 Approximately 10 10 Approximately 10 11 Or about 10 12 Virus at PFU / mL.

[0130] Pharmaceutical compositions and formulations can be prepared by mixing one or more active ingredients (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 recipients at the doses and concentrations used and may include, but are not limited to: buffers (such as phosphates, citrates, acetates, and other organic acids); antioxidants (such as ascorbic acid and methionine); preservatives (such as octadecyl dimethyl benzyl ammonium chloride, benzalkonium chloride, benzyl chloride, phenol, butanol or benzyl alcohol, alkyl p-hydroxybenzoate, 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) peptides; proteins (such as serum...). Albumin, gelatin, or immunoglobulins; polyols (such as glycerol, for example, formulations containing 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15% glycerol); hydrophilic polymers (such as polyvinylpyrrolidone); monosaccharides, disaccharides, and other carbohydrates (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 zinc-protein complexes); and / or nonionic surfactants (such as polyethylene glycol (PEG)). A thorough discussion of pharmaceutically acceptable carriers is available in REMINGTON'S PHARMACEUTICALSCIENCES (Mack Pub. Co., NJ 1991).

[0131] In some embodiments, the pharmaceutical composition or formulation is suitable as eye drops, ointments, pastes, creams, suspensions, emulsions, fat ointments, gels, bioadhesive gels, powders, lotions, solutions and / or sprays.

[0132] 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 drug delivery media of submicron (less than about 1000 nm) size that can carry 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 methods well known in the art. In some embodiments, "molecules encapsulated in nanoparticles" can refer to molecules (such as viruses) contained within the nanoparticles or attached to and / or associated with the surface of the nanoparticles, or any combination thereof. The nanoparticles used in the compositions or formulations described herein may be any type of biocompatible nanoparticles known in the art, including, for example, nanoparticles comprising 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; US 2007 / 0148074; US 2007 / 0092575; US 2006 / 0246139; US 5753234; US 7081483; and WO 2006 / 052285).

[0133] In some embodiments, a pharmaceutically acceptable carrier or excipient may be suitable for or adapted to any route of administration known in the art, including, for example, ocular, subretinal, intraocular, vitreous, topical, subcutaneous, subconjunctival, subfascial, subcapsular, anterior chamber, retrobulbar, systemic, extra-gastric, periorbital, scleral, anterior scleral, posterior scleral, oral, peribulbar, or choroidal administration.

[0134] In some embodiments, a pharmaceutically acceptable carrier or excipient may be suitable for or adapted to any route of administration known in the art, including, for example, intravenous, intramuscular, subcutaneous, skin, oral, intranasal, intratracheal, sublingual, buccal, topical, percutaneous, intradermal, intraperitoneal, intraorbital, intravitreal, subretinal, suprachoroidal, transmucosal, intra-articular, via implantation, via inhalation, intrathecal, intraventricular, and / or intranasal administration.

[0135] In some embodiments, the pharmaceutical composition or formulation is suitable for any route of administration known in the art, including, for example, intravenous, intramuscular, subcutaneous, skin, oral, intranasal, intratracheal, sublingual, buccal, topical, percutaneous, intradermal, intraperitoneal, intraorbital, intravitreal, subretinal, suprachoroidal, transmucosal, intra-articular, via implantation, via inhalation, intrathecal, intraventricular, or intranasal administration.

[0136] In some embodiments, the pharmaceutical composition or formulation further comprises one or more additional components. Examples of additional components 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, ethyl cellulose, polyacrylate, or dicalcium phosphate); lubricants (e.g., magnesium stearate, talc, silica, colloidal silica, stearic acid, metal stearates, hydrogenated vegetable oils, corn starch, polyethylene glycol, sodium benzoate, sodium acetate, etc.); disintegrants (e.g., starch, sodium carboxyacetic acid starch, etc.); wetting agents (e.g., sodium dodecyl sulfate, etc.); salt solutions; alcohols; polyethylene glycol; gelatin; lactose; amylase; magnesium stearate; talc; silicic acid; viscous paraffin; hydroxymethylcellulose; polyvinylpyrrolidone; sweeteners; flavoring agents; fragrances; coloring agents; humectants; sunscreens; antibacterial agents; and pharmaceutical agents capable of stabilizing or preventing the degradation of polynucleotides. In some embodiments, the pharmaceutical composition or formulation comprises methylcellulose gel (e.g., hydroxypropyl methylcellulose, carboxymethylcellulose, etc.). In some embodiments, the pharmaceutical composition or formulation comprises phosphate buffer. In some embodiments, the pharmaceutical composition or formulation comprises glycerol (e.g., at 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 both phosphate buffer and glycerol.

[0137] Pharmaceutical compositions and formulations intended for internal administration are typically sterile. Sterility can be readily achieved, for example, through filtration via a sterile filter membrane.

[0138] In some embodiments, any of the recombinant nucleic acids, viruses, and / or pharmaceutical compositions or formulations described herein can be used to deliver one or more polynucleotides encoding polypeptides to one or more cells of a subject (e.g., one or more cells of the subject's eye). 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 used to treat retinitis pigmentosa, latent retinitis pigmentosa, severe latent retinitis pigmentosa, overt retinitis pigmentosa, overt retinitis pigmentosa with choroidal involvement, latent retinitis pigmentosa with para-arteriolar retinopathy (PPRPE), latent retinitis pigmentosa with posterior column ataxia (PCARP), latent retinitis pigmentosa with microcytosis, syndromic latent retinitis pigmentosa, latent syndromic disease with retinitis pigmentosa, non-syndromic latent retinitis pigmentosa, and non-syndromic retinitis pigmentosa. Dominant retinitis pigmentosa, syndromic dominant retinitis pigmentosa, juvenile latent retinitis pigmentosa, latent retinitis pigmentosa with intellectual disability, latent retinitis pigmentosa with macular degeneration, severe early-onset latent retinitis pigmentosa, latent retinitis pigmentosa with skeletal abnormalities, latent retinitis pigmentosa with skeletal deformities, dominant retinitis pigmentosa with sensorineural hearing loss, latent retinitis pigmentosa with hearing loss, latent retinitis pigmentosa with hearing loss and other impairments, latent retinitis pigmentosa with vitreous changes, early-onset latent retinitis pigmentosa with macular defects, X-linked retinitis pigmentosa, latent X-linked retinitis pigmentosa. 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, Bald-Biedel syndrome-like retinitis pigmentosa, Bald-Biedel syndrome-like latent retinitis pigmentosa, bigenic retinitis pigmentosa, bigenic retinitis pigmentosa due to abnormality of outer retinal membrane protein 1, bigenic retinitis pigmentosa due to abnormality of PRPH2, latent retinitis pigmentosa with early macular involvement, latent deafness without retinitis pigmentosa, latent congenital deafness without retinitis pigmentosa, latent retinitis pigmentosa Retinitis pigmentosa with recessive ataxia, recessive retinitis pigmentosa with 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 deafness and neurological abnormalities, autosomal dominant retinitis pigmentosa, non-syndromic 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,Latent ataxia, overt ataxia, Sinier-Lukehn syndrome, latent Sinier-Lukehn syndrome, overt Sinier-Lukehn syndrome, renal wasting disease, latent renal wasting disease, overt renal wasting disease, juvenile latent renal wasting disease, ciliopathy-associated latent renal wasting disease, juvenile renal wasting disease, juvenile latent renal wasting disease, juvenile overt renal wasting disease, Usher syndrome, Usher syndrome type I, Usher syndrome type II, Usher syndrome type III, latent Usher syndrome, atypical latent Usher syndrome, overt Usher syndrome, type 2 latent Usher syndrome, type 2a latent Usher syndrome, type 3 latent Usher syndrome, type 3-like latent Usher syndrome, atypical latent Usher syndrome, type 1 latent Usher syndrome, type 1b latent Usher syndrome Recessive Irsell syndrome, type 1d recessive Irsell syndrome, type 1f recessive Irsell syndrome, type 1J recessive Irsell syndrome, type 1k recessive Irsell syndrome, bigenic Irsell syndrome due to CDH23 abnormality, bigenic Irsell syndrome due to PCDH15 abnormality, Acadia recessive Irsell syndrome, recessive atypical Irsell syndrome (USH3-like), Leber congenital amaurosis, recessive Leber congenital amaurosis, dominant Leber congenital amaurosis, new-onset Leber congenital amaurosis, dominant Leber congenital amaurosis with 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 atrophy, recessive optic atrophy Dominant optic atrophy, optic atrophy with ataxia, latent optic atrophy with ataxia, dominant optic atrophy with ataxia, latent optic atrophy with ataxia and 3-methylpentanoic aciduria, dominant optic atrophy with cataracts, ataxia and areflexia, Kaiser type dominant optic atrophy, dominant optic atrophy with sensorineural hearing loss, latent cerebellar degeneration with optic atrophy, optic atrophy with deafness-dystonia syndrome, X-linked optic atrophy with deafness-dystonia syndrome, retinal dystrophy, latent retinal dystrophy, dominant retinal dystrophy, hereditary retinal dystrophy, early-onset latent retinal dystrophy, latent syndromic retinal dystrophy, latent non-syndromic retinal dystrophy Retinal dystrophy, latent syndromic retinal dystrophy, latent optic atrophy with retinal dystrophy, latent retinal dystrophy with obesity, latent retinal dystrophy with cerebellar dysplasia, syndromic latent optic atrophy with retinal dystrophy, overt retinal dystrophy with iris defects, ciliary spectrum disorders including retinal dystrophy, latent ciliary spectrum disorders including retinal dystrophy, overt ciliary spectrum disorders including retinal dystrophy, overt optic atrophy with neuropathy and myopathy, overt optic atrophy with intellectual disability and developmental delay, syndromic optic atrophy, non-syndromic optic atrophy, latent non-syndromic optic atrophy, overt non-syndromic optic atrophy.Latent symptom optic atrophy, overt symptom optic atrophy, Charcot-Marie-Tuss disease, latent Charcot-Marie-Tuss disease, overt Charcot-Marie-Tuss disease, benign punctate retinopathy, latent benign punctate retinopathy, overt benign punctate retinopathy, symptom syndrome, latent symptom syndrome, overt symptom syndrome, Barten disease, latent Barten disease, overt Barten disease, latent Barten disease (neuronal ceroid lipofuscinosis type 3), juvenile latent Barten disease (neuronal ceroid lipofuscinosis type 3), neuronal ceroid lipofuscinosis, latent neuronal ceroid lipofuscinosis, latent neuronal ceroid lipofuscinosis type 1, overt neuronal ceroid lipofuscinosis, Staggart disease, latent Staggart disease Dominant Statart disease, Juvenile Statart disease, Late-onset Statart disease, Statart disease-like macular dystrophy, Latent Statart disease-like macular dystrophy, Dominant Statart disease-like macular dystrophy, Macular dystrophy, Latent macular dystrophy, Early-onset macular dystrophy, Adult-onset macular dystrophy, Early-onset latent macular dystrophy, Adult-onset latent macular dystrophy, Early-onset adult-onset latent macular dystrophy, Juvenile latent macular dystrophy with sparse hairs, Dominant macular dystrophy, Late-onset dominant macular dystrophy, Dominant macular dystrophy with lens suspensory ligament abnormalities, Bull's-eye dominant macular dystrophy, Butterfly-shaped dominant macular dystrophy, Age-related dominant macular dystrophy, Benign concentric ring dominant macular dystrophy Malnutrition, ovumoid latent macular dystrophy, ovumoid dominant macular dystrophy, atypical ovumoid dominant macular dystrophy, dominant adult-onset ovumoid macular dystrophy, Staggart's disease-like dominant macular dystrophy, Staggart's disease-type dominant macular dystrophy, North Carolina-type dominant macular dystrophy, North Carolina-type dominant macular dystrophy, North Carolina-type dominant macular dystrophy with progressive sensorineural hearing loss, cystoid dominant macular dystrophy, Best type dominant macular dystrophy, latent macular dystrophy, latent latent macular dystrophy, dominant latent macular dystrophy, age-related familial macular dystrophy, X-linked atrophic macular dystrophy, latent X-linked atrophic macular dystrophy Malnutrition, dominant X-linked macular atrophy, mitochondrial macular pattern malnutrition with type II diabetes and deafness, macular degeneration, latent macular degeneration, dominant macular degeneration, rod malnutrition, latent rod malnutrition, dominant rod malnutrition, cone malnutrition, latent cone malnutrition, dominant cone malnutrition, latent cone malnutrition with abnormal electroretinogram of rods, early-onset latent cone malnutrition, late-onset latent cone malnutrition, cone malnutrition type 1, X-linked cone malnutrition type 1, cone malnutrition type 2, progressive cone malnutrition type 2, X-linked progressive cone malnutrition type 2, delayed cone adaptation, delayed latent cone adaptation, delayed dominant cone adaptation.Cone-rod dystrophy, latent cone-rod dystrophy, manifest cone-rod dystrophy, isolated cone-rod dystrophy, progressive cone-rod dystrophy, X-linked cone-rod dystrophy, X-linked progressive cone-rod dystrophy, progressive manifest cone-rod dystrophy, cone-rod dystrophy with enamel hypoplasia syndrome, latent cone-rod dystrophy with enamel hypoplasia syndrome, manifest cone-rod dystrophy with enamel hypoplasia syndrome, latent cone-rod dystrophy with inner retinal disease, latent cone-rod dystrophy with skeletal disease, congenital syndrome of non-progressive latent cone-rod dystrophy, latent cone-rod dystrophy with hearing loss. Latent cone-rod dystrophy with psychomotor delay, latent cone with cone-rod dystrophy, cone-rod synaptic disorders, congenital cone-rod synaptic disorders, latent congenital cone-rod synaptic disorders, dominant congenital cone-rod synaptic disorders, rod-cone dystrophy, latent rod-cone dystrophy, dominant rod-cone dystrophy, early-onset latent rod-cone dystrophy, non-syndromic latent rod-cone dystrophy, latent Newfoundland type rod-cone dystrophy, latent progressive cone dystrophy, Stickler syndrome, dominant Stickler syndrome, latent Stickler syndrome, dominant Stickler syndrome type I, dominant Stickler syndrome type II, Marshall syndrome, dominant Marshall syndrome Latent Marshall syndrome, achromatopsia, latent achromatopsia, manifest achromatopsia, latent complete achromatopsia, latent incomplete achromatopsia, macular degeneration, age-related macular degeneration, age-related macular degeneration of complex etiologies, isolated age-related macular degeneration, wet age-related macular degeneration, dry age-related macular degeneration, drusen, latent drusen, manifest drusen, early-onset latent drusen, early-onset manifest drusen, macular drusen, manifest radial macular drusen, pigmented paravenous choroidal retinal atrophy, latent pigmented paravenous choroidal retinal atrophy, manifest pigmented paravenous choroidal retinal atrophy, progressive bifocal choroidal retinal atrophy, Balder-Biedel syndrome, latent Balder-Biedel syndrome Symptoms, dominant Baldr-Beedel syndrome, latent Baldr-Beedel syndrome with developmental abnormalities, retinal degeneration, latent retinal degeneration, dominant retinal degeneration, non-syndromic latent retinal degeneration, multifactorial celluloid retinal degeneration, latent multifactorial celluloid retinal degeneration, dominant multifactorial celluloid retinal degeneration (Leventinese disease), latent renal wasting disease with retinal degeneration, Alstrom syndrome, latent Alstrom syndrome, dominant Alstrom syndrome, Joubert syndrome, latent Joubert syndrome, dominant Joubert syndrome, Jobel syndrome, latent Jobel syndrome, dominant Jobel syndrome, X-linked Jobel syndrome, vitreoretinal degeneration, latent vitreoretinal degeneration, dominant vitreoretinal degeneration.Snowflake-like vitreoretinal degeneration, snowflake-like manifest vitreoretinal degeneration, microstomia, latent microstomia, manifest microstomia, night blindness, stationary night blindness, congenital night blindness, congenital stationary night blindness, severe congenital stationary night blindness, latent congenital stationary night blindness, latent complete congenital stationary night blindness, manifest congenital stationary night blindness, Nogarette type manifest congenital stationary night blindness, microstomia type latent congenital stationary night blindness, Riggs type latent congenital stationary night blindness, Schubert-Bornshain type latent congenital stationary night blindness, white spot fundus type latent congenital stationary night blindness, complete latent congenital stationary night blindness, X-linked congenital stationary night blindness, incomplete X-linked congenital Still night blindness, retinal vascular disease, leukodystrophy, retinal vascular disease with leukodystrophy, latent retinal vascular disease with leukodystrophy, overt retinal vascular disease with leukodystrophy, Ecardi-Gutier syndrome, Ecardi-Gutier syndrome type 1, latent Ecardi-Gutier syndrome type 1, overt Ecardi-Gutier syndrome type 1, frostbite-like lupus, latent frostbite-like lupus, overt frostbite-like lupus, Martinique retinal dystrophy with retinitis pigmentosa, latent Martinique retinal dystrophy with retinitis pigmentosa, overt Martinique retinal dystrophy with retinitis pigmentosa, spinocerebellar ataxia, latent spinocerebellar ataxia, overt spinocerebellar ataxia Cerebral ataxia, spinocerebellar ataxia with macular dystrophy, spinocerebellar ataxia with retinal degeneration, spinocerebellar ataxia with macular dystrophy or retinal degeneration, latent spinocerebellar ataxia with macular dystrophy or retinal degeneration, overt spinocerebellar ataxia with macular dystrophy or retinal degeneration, Wolfram syndrome, latent Wolfram syndrome, overt Wolfram syndrome, low-frequency sensorineural hearing loss, latent low-frequency sensorineural hearing loss, overt low-frequency sensorineural hearing loss, oculo-auricular syndrome, latent oculo-auricular syndrome, overt oculo-auricular syndrome, latent kidney, skeletal and retinal abnormalities, latent abeloinemia, microcephaly, latent microcephaly, overt microcephaly. Growth retinal dysplasia with retinal disease, petechiae lenticulosclerotic keratoretinal dystrophy, petechiae lenticulosclerotic keratoretinal dystrophy, petechiae lenticulosclerotic keratoretinal dystrophy, petechiae lenticulosclerotic keratoretinal dystrophy, wagner's disease, erosive vitreoretinopathy, wagner's disease with erosive vitreoretinopathy, petechiae wagner's disease with erosive vitreoretinopathy, petechiae wagner's disease with erosive vitreoretinopathy, petechiae wagner's disease with erosive vitreoretinopathy, petechiae wagner's disease with erosive vitreoretinopathy, febrile seizures, petechiae facultative febrile seizures, petechiae facultative febrile seizures, petechiae facultative febrile seizures, petechiae facultative febrile seizures, petechiae facultative febrile seizures, petechiae facultative febrile seizures, choroidal dystrophy, petechiae facultative ...Latent epiphyseal dysplasia, dominant epiphyseal dysplasia, multiple epiphyseal dysplasia, latent multiple epiphyseal dysplasia, dominant multiple epiphyseal dysplasia, ichthyosis, latent ichthyosis, dominant ichthyosis, latent ichthyosis with quadriplegia and flaccidity, choroidal-retinal atrophy, bifocal choroidal-retinal atrophy, progressive bifocal choroidal-retinal atrophy, latent progressive bifocal choroidal-retinal atrophy, dominant progressive bifocal choroidal-retinal atrophy, Rife's disease, latent Rife's disease, dominant Rife's disease, adult latent Rife's disease, infantile latent Rife's disease, retinal-cone dystrophy, latent retinal-cone dystrophy, dominant retinal-cone dystrophy, retinal-cone dystrophy type 1, latent vision Retinal-cone dystrophy type 1, dominant retinal-cone dystrophy type 1, blue-yellow color blindness, latent blue-yellow color blindness, dominant blue-yellow color blindness, mucopolysaccharidosis, latent mucopolysaccharidosis, dominant mucopolysaccharidosis, Pinglapa achromatopsia, latent Pinglapa achromatopsia, dominant Pinglapa achromatopsia, Krippel-Fair syndrome, latent Krippel-Fair syndrome, dominant Krippel-Fair syndrome, microphthalmia, latent microphthalmia, dominant microphthalmia, limb-girdle muscular dystrophy, latent limb-girdle muscular dystrophy, dominant limb-girdle muscular dystrophy, short-rib thoracic dysplasia, latent short-rib thoracic dysplasia, dominant short-rib thoracic dysplasia, latent short-rib thoracic dysplasia with polydactyly, latent short-rib thoracic dysplasia with retinal dystrophy Poor development, intellectual disability, truncal obesity, retinal dystrophy, micropenis (MORM) syndrome, latent MORM syndrome, dominant MORM syndrome, latent retinal delay with spasticity and retinal degeneration, Cockayne syndrome, latent Cockayne syndrome, dominant Cockayne syndrome, congenital retinal detachment, latent nonsyndromic congenital retinal detachment, dominant nonsyndromic congenital retinal detachment, hemolytic anemia, nonspherocytic hemolytic anemia, latent nonspherocytic hemolytic anemia, dominant nonspherocytic hemolytic anemia, hereditary neuropathy, hereditary neuropathy (Russian type), latent hereditary neuropathy (Russian type), dominant hereditary neuropathy (Russian type), choroidal sclerosis, latent choroidal sclerosis, dominant Choroidal sclerosis, retinopathy, latent retinopathy, manifest retinopathy, combined manifest and latent retinopathy, diffuse manifest retinopathy, variant manifest retinopathy, diffuse manifest retinopathy with variants, microcephaly, latent microcephaly, manifest microcephaly, manifest microcephaly with lymphedema, manifest microcephaly with choroidal retinal disease, manifest microcephaly with lymphedema and choroidal retinal disease, choroidal retinal disease, latent choroidal retinal disease, manifest choroidal retinal disease, choroidal retinal disease with microcephaly, latent choroidal retinal disease with microcephaly, manifest choroidal retinal disease with microcephaly, renal defect syndrome, latent renal defect syndrome, manifest renal defect syndrome.Non-syndromic hearing loss, latent non-syndromic hearing loss, overt non-syndromic hearing loss, cycloidal atrophy, latent cycloidal atrophy, overt cycloidal atrophy, cycloidal choroidal atrophy, vitreoretinal disease, exudative vitreoretinal disease, familial exudative vitreoretinal disease, latent familial exudative vitreoretinal disease, overt familial exudative vitreoretinal disease, overt familial exudative vitreoretinal disease with Kurtz's disease, neovascularization vitreoretinal disease, latent neovascularization vitreoretinal disease, overt neovascularization vitreoretinal disease, macular atrophy, latent macular atrophy, overt macular atrophy, Merkel syndrome, latent Merkel syndrome, overt Merkel syndrome, vitreous choroidal atrophy Vitreoretinal-choroidal diseases, latent vitreoretinal-choroidal diseases, overt vitreoretinal-choroidal diseases, ovarian macular degeneration, latent ovarian macular degeneration, overt ovarian macular degeneration, high bone mass trait, latent high bone mass trait, overt high bone mass trait, osteoporosis-pseudoglioma syndrome, latent osteoporosis-pseudoglioma syndrome, overt osteoporosis-pseudoglioma syndrome, microphthalmia, latent microphthalmia, overt microphthalmia, retinal disease syndrome, latent retinal disease syndrome, overt retinal disease syndrome, microphthalmia with retinal disease syndrome, latent microphthalmia with retinal disease syndrome, overt microphthalmia with retinal disease syndrome, true microphthalmia, latent true microphthalmia, overt true microphthalmia, skeleton Developmental dysplasia, occult skeletal dysplasia, overt skeletal dysplasia, developmental disorders, osteoarthritis with syndromic disorders, cavitary optic disc abnormalities, occult cavitary optic disc abnormalities, overt cavitary optic disc abnormalities, white spot fundus, occult white spot fundus, overt white spot fundus, mevalonateuria, occult mevalonateuria, overt mevalonateuria, high IgD syndrome, occult high IgD syndrome, overt high IgD syndrome, spastic paraplegia, occult spastic paraplegia, overt spastic paraplegia, occult spastic paraplegia with neuropathy, occult spastic paraplegia with optic nerve atrophy, occult spastic paraplegia with optic nerve atrophy (dementia), occult dementia, overt dementia, familial overt dementia, retinoblastoma. Latent retinoblastoma, dominant retinoblastoma, germ cell retinoblastoma, somatic cell retinoblastoma, dominant germ cell or somatic cell retinoblastoma, retinaculum, benign retinaculum, pineal tumor, osteosarcoma, rod monochromatic vision, latent rod monochromatic vision, dominant rod monochromatic vision, total color blindness, latent total color blindness, dominant total color blindness, rod total color blindness, rod latent total color blindness, rod dominant total color blindness, latent rod monochromatic vision or total color blindness, figure-like dystrophy, latent figure-like dystrophy, dominant figure-like dystrophy, S-cone syndrome, enhanced S-cone syndrome (ESC), latent ESC, dominant ESC, Goldman-Favre syndrome, latent Goldman-Favre syndrome,Dominant Goldman-Favre syndrome, Portinia type malnutrition, Latent Portinia type malnutrition, Dominant Portinia type malnutrition, White spot retinal degeneration, Latent white spot retinal degeneration, Dominant white spot retinal degeneration, Mucinous storage disease type IIIγ, Latent mucinous storage disease type IIIγ, Dominant mucinous storage disease type IIIγ, Meinzel-Saldino syndrome, Latent Meinzel-Saldino syndrome, Dominant Meinzel-Saldino syndrome, Pseudoxanoma elasticum, Latent pseudoxanoma elasticum, Dominant pseudoxanoma elasticum, Knobloch syndrome, Latent Knobloch syndrome, Dominant Knobloch syndrome, Foveal dysplasia, Latent foveal dysplasia, Dominant foveal dysplasia, Anterior segment dysplasia, Latent anterior segment dysplasia, dominant anterior segment dysplasia, foveal dysplasia with anterior segment dysplasia, latent foveal dysplasia with anterior segment dysplasia, dominant foveal dysplasia with anterior segment dysplasia, spastic ataxia, latent spastic ataxia, dominant spastic ataxia, Degroove syndrome, Boucher-Neuhauser syndrome, latent Boucher-Neuhauser syndrome, dominant Boucher-Neuhauser syndrome, Boucher-Neuhauser syndrome with choroidal-retinal dystrophy, latent Boucher-Neuhauser syndrome with choroidal-retinal dystrophy, dominant Boucher-Neuhauser syndrome with choroidal-retinal dystrophy, hypo-pre-β-lipoproteinemia-acanthocytosis-retinitis pigmentosa-globus pallidus (HARP) degeneration Latent HARP degeneration, dominant HARP degeneration, Hallewarden-Schpattz syndrome, latent Hallewarden-Schpattz syndrome, dominant Hallewarden-Schpattz syndrome, Arager syndrome, latent Arager syndrome, dominant Arager syndrome, polyneuropathy-hearing loss-ataxia-retinitis pigmentosa-early-onset cataract (PHARC), latent PHARC, dominant PHARC, latent syndromic PHARC, Sotheby's retinal dystrophy, latent Sotheby's retinal dystrophy, dominant Sotheby's retinal dystrophy, vitreoretinal dystrophy, latent vitreoretinal dystrophy, dominant vitreoretinal dystrophy, optic neuropathy, latent optic neuropathy, dominant optic neuropathy Modified, late-onset dominant optic neuropathy, orofacial-finger syndrome type 1, Simpson-Goraby-Bemmel syndrome type 2, X-linked retinoschisis, X-linked Oregon type eye disease, X-linked optic atrophy, retinal dysplasia, latent retinal dysplasia, dominant retinal dysplasia, X-linked retinal dysplasia, primary X-linked retinal dysplasia, X-linked Norrie's disease, Coulter's disease, X-linked Isle of Orlando eye disease, autoimmune inner ear disease (AIED), AIED-like disease, achoroidal disease, X-linked achoroidal disease, neuropathy-optic atrophy-deafness-retinitis pigmentosa, X-linked neuropathy-optic atrophy-deafness-retinitis pigmentosa, X-linked blue cone monochromatic vision,X-linked red-blindness with rare macular dystrophy and blue cone monochromatic vision (BCM), X-linked green-blindness with rare macular dystrophy and blue cone monochromatic vision (BCM), including mitochondrial Karns-Sell syndrome of retinitis pigmentosa, Leigh syndrome, retinopathy, mitochondrial retinopathy with sensorineural hearing loss, ocular albinism, oculocutaneous albinism, neuronal ceroid lipofuscin deposition, Zelweg spectrum disorder, cobalamin C deficiency, hereditary red-green color vision deficiency of blue cone monochromatic vision, blue blindness with yellow-blue color vision deficiency, visual impairment, delayed cone adaptation, uveitis, diabetic retinopathy, diabetic macular edema, persistent corneal epithelial defects, neurotrophic keratitis, herpetic stromal keratitis, chronic dry eye Eye diseases, glaucoma, eye abrasion, eye bullae formation, eye scarring, vision loss, blindness, corneal blindness, dry eye syndrome, aqueous-deficient dry eye syndrome, Sjögren's syndrome-related aqueous-deficient dry eye syndrome, non-Sjögren's syndrome-related dry eye syndrome, evaporative dry eye syndrome, meibomian gland dysfunction, blepharitis, blepharitis, ocular erythema with atopic dermatitis, aqueous-deficient dry eye syndrome with evaporative dry eye syndrome, Fuchs' dystrophy, Fuchs' corneal endothelial dystrophy (FECD), Fuchs' endothelial dystrophy (FED), panuveitis, diffuse uveitis, complete uveitis, cataract, partial cataract, complete cataract, stationary cataract, progressive cataract, hard cataract, soft cataract, nuclear cataract, nuclear sclerotic cataract, cortical cataract Congenital cataract, posterior subcapsular cataract, congenital cataract, corneal dystrophy, epithelial with subepithelial dystrophy, epithelial basement membrane dystrophy, recurrent epithelial erosive dystrophy (Francescatie dystrophy, Smorandi dystrophy and / or Helsinglandia dystrophy), subepithelial myxoid dystrophy, Missmann dystrophy, Lich epithelial dystrophy, droplet dystrophy, Bowman's stratum corneum dystrophy, Les-Bukler's dystrophy, Thiel-Bunker's dystrophy, stromal dystrophy-TGFB1 dystrophy, reticular dystrophy, reticular dystrophy type 1 variants (type III, type IIIA, type I / IIIA, type IV), granular dystrophy Type 1 keratodystrophy, Type 2 granular keratodystrophy, stromal dystrophy, macular keratodystrophy, Schneider crystalline keratodystrophy, congenital stromal keratodystrophy, punctate keratodystrophy, amorphous posterior keratodystrophy, François central cloud keratodystrophy, Desmi anterior keratodystrophy, endothelial dystrophy, Fuchs keratodystrophy, polymorphic posterior keratodystrophy, congenital hereditary endothelial dystrophy, X-linked endothelial keratodystrophy, superficial superficial keratodystrophy, epithelial basement membrane keratodystrophy, Missmann juvenile epithelial keratodystrophy, droplet keratodystrophy, Lich epithelial keratodystrophy, subepithelial mucinous keratodystrophy, Les-Buklers keratodystrophy, Till-Bunk keratodystrophy.Stroma dystrophy, reticular keratopathy, granular keratopathy, macular keratopathy, Schneider's crystalline keratopathy, congenital stromal keratopathy, punctate keratopathy, posterior keratopathy, Fuchs keratopathy, polymorphic posterior keratopathy, congenital hereditary endothelial dystrophy, corneal diseases, band keratopathy, corneal band keratopathy and / or calcified band keratopathy.

[0139] In some implementations, one or more transgenes include genes expressed in the photoreceptors of the subject.

[0140] In some embodiments, the disease or condition is Staggart disease. In some embodiments, one or more symptoms include central vision loss beginning in childhood or early adolescence. In some embodiments, the disease or condition is autosomal recessive. In some embodiments, the disease or condition involves one or more mutations in ABCA4. In some embodiments, the prevalence of the disease or condition is approximately 1 in 10,000. Mutations in ABCA4 also cause cone-rod dystrophy (loss of visual acuity, photophobia, impaired color vision), which worsens over time and is also autosomal recessive. In some embodiments, the disease or condition involves one or more mutations in ELOVL4. For example, Staggart disease may also be rarely caused by mutations in the ELOVL4 gene.

[0141] In some embodiments, the disease or condition is retinitis pigmentosa. In some embodiments, one or more symptoms encompass a wide range of severity, some beginning in childhood and others in late adulthood, depending on the mutation. In some embodiments, one or more symptoms include night blindness, peripheral vision loss, and / or symptoms that eventually affect central vision. In some embodiments, the disease or condition is caused by one or more gene mutations. In some embodiments, the disease or condition involves approximately 60 gene mutations. In some embodiments, the disease or condition involves one or more autosomal dominant mutations in the RHO, which may account for approximately 20%-30% of cases. In some embodiments, the disease or condition involves one or more autosomal recessive mutations in USH2A (Usher syndrome type II), which may account for approximately 10%-15% of cases and have a prevalence of approximately 4 / 100,000. In some embodiments, one or more symptoms begin in late adolescence / early adulthood. In some embodiments, the prevalence of the disease or condition is approximately 1 / 4,000.

[0142] In some implementations, one or more transgenes include genes expressed in the subject's retinal pigment epithelium (RPE) cells.

[0143] In some embodiments, the disease or condition is Leber congenital amaurosis (LCA). In some embodiments, one or more symptoms include severe visual impairment beginning in infancy. In some embodiments, the disease or condition is autosomal recessive. In some embodiments, the prevalence of the disease or condition is approximately 2 / 100,000. In some embodiments, the disease or condition involves one or more mutations in RPE65 and / or CEP290. Other major gene mutation populations are genes that are primarily expressed in photoreceptors but not in RPE cells.

[0144] In some embodiments, the disease or condition is white spot fundus. 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 stationary night blindness. In some embodiments, the disease or condition involves one or more mutations in the RDH5 gene in RPE cells.

[0145] In some embodiments, the disease or condition is white spot retinal degeneration. In some embodiments, one or more symptoms may begin in childhood and may include night blindness. In some embodiments, the disease or condition is autosomal recessive. In some embodiments, the prevalence of the disease or condition in individuals with autosomal recessive RCD is approximately 1% (1 in 800,000 individuals worldwide). In some embodiments, the disease or condition involves one or more mutations in RLBP1.

[0146] 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 prevalence of the disease or condition in patients with hereditary retinal dystrophy (IRD) is approximately 2%, where the prevalence of IRD is approximately 1 in 2000.

[0147] In some implementations, the disease or condition or its symptoms may include any one or more of the following: Staggart disease; Leber congenital amaurosis; early-onset severe retinopathy; retinitis pigmentosa; non-syndromic retinitis pigmentosa; Usher syndrome type 1-3; Betty crystalline keratoretinal dystrophy; congenital stationary night blindness; white spot fundus; white spot retinal degeneration; choroidal agenesis; achromatopy; retinal manifestations of Alstrom syndrome; Balde-Beidel syndrome; Jubert syndrome; cycloplegic choroidal atrophy; X-linked congenital retinoschisis; progressive bifocal choroidal atrophy; retinoblastoma; uveitis; diabetic retinopathy; diabetic macular edema; persistent corneal epithelial defects; neurotrophic keratitis; chronic dry eye; wet AMD; dry AMD; geographical atopy; and glaucoma.

[0148] In some embodiments, this document provides compositions, methods, and uses for gene therapy of eye disorders. In some embodiments, the recombinant HSV genome or HSV can be used for topical application. VI. Methods

[0149] Certain aspects of this disclosure relate to a method of delivering a polypeptide to one or more cells of a subject (e.g., one or more cells of the eye, such as the 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; Miller cells; amacrine cells, etc.), said method comprising administering a pharmaceutical composition to the subject comprising (a) any virus described herein (e.g., herpes simplex virus, such as HSV-1) and a pharmaceutically acceptable vector, said virus comprising any recombinant nucleic acid described herein (e.g., recombinant herpes simplex virus genome, such as recombinant HSV-1 genome), said recombinant nucleic acid comprising one or more polynucleotides encoding a polypeptide. In some embodiments, the pharmaceutical composition is administered to a subject via injection, injection into the eye, subretinal injection, intraocular injection, intravitreal injection, suprachoroidal injection, intraanterior chamber injection, intraocular injection, intravitreal injection, topical injection, subcutaneous injection, subconjunctival injection, subfascial injection, intraanterior chamber injection, retrobulbar injection, systemic injection, parenteral injection, periocular injection, near the sclera, anterior near the sclera, posterior near the sclera, oral administration, peribulbar injection, or suprachoroidal injection. 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 replicative. In some embodiments, the herpesvirus (e.g., herpes simplex virus) is replication-deficient. In some embodiments, the herpesvirus (e.g., herpes simplex virus) is not oncolytic.

[0150] In some implementations, the subject is a person. In some implementations, the subject has an eye condition or disease. In some implementations, the eye condition or disease is selected from retinitis pigmentosa, latent retinitis pigmentosa, severe latent retinitis pigmentosa, overt retinitis pigmentosa, overt retinitis pigmentosa with choroidal involvement, latent retinitis pigmentosa with para-arteriolar RPE preservation (PPRPE), latent retinitis pigmentosa with posterior column ataxia (PCARP), latent retinitis pigmentosa with microcytic polycythemia, syndromic latent retinitis pigmentosa, latent syndromic disease with retinitis pigmentosa, non-syndromic latent retinitis pigmentosa, non-syndromic overt retinitis pigmentosa, syndromic overt retinitis pigmentosa, juvenile latent retinitis pigmentosa, latent retinitis pigmentosa. Retinitis pigmentosa with intellectual disability, latent retinitis pigmentosa with macular degeneration, severe early-onset latent retinitis pigmentosa, latent retinitis pigmentosa with skeletal abnormalities, latent retinitis pigmentosa with skeletal deformities, overt retinitis pigmentosa with sensorineural hearing loss, latent retinitis pigmentosa with hearing loss, latent retinitis pigmentosa with hearing loss and other impairments, latent retinitis pigmentosa with vitreous changes, early-onset latent retinitis pigmentosa with macular defects, X-linked retinitis pigmentosa, latent X-linked retinitis pigmentosa, overt X-linked retinitis pigmentosa, severe X-linked retinitis pigmentosa, X-linked retinitis pigmentosa with intellectual disability, X-linked retinitis pigmentosa Retinitis pigmentosa with myopathy, Bald-Biedel syndrome-like retinitis pigmentosa, Bald-Biedel syndrome-like latent retinitis pigmentosa, bigenic retinitis pigmentosa, bigenic retinitis pigmentosa due to abnormality of outer retinal membrane protein 1, bigenic retinitis pigmentosa due to abnormality of PRPH2, latent retinitis pigmentosa with early macular involvement, latent deafness without retinitis pigmentosa, latent congenital deafness without retinitis pigmentosa, latent retinitis pigmentosa with latent ataxia, latent retinitis pigmentosa with dominant ataxia, mitochondrial retinitis pigmentosa, mitochondrial retinitis pigmentosa with developmental and neurological abnormalities, mitochondrial retinitis pigmentosa with progressive sensory impairment. Transient hearing loss, mitochondrial retinitis pigmentosa with deafness and neurological abnormalities, autosomal dominant retinitis pigmentosa, non-syndromic 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, Sinier-Lukehn syndrome, recessive Sinier-Lukehn syndrome, dominant Sinier-Lukehn syndrome, renal wasting disease, recessive renal wasting disease, dominant renal wasting disease, juvenile recessive renal wasting disease, ciliopathy-associated recessive renal wasting disease, juvenile renal wasting disease,Juvenile latent renal wasting disease, juvenile dominant renal wasting disease, Usher syndrome, Usher syndrome type I, Usher syndrome type II, Usher syndrome type III, latent Usher syndrome, atypical latent Usher syndrome, dominant Usher syndrome, type 2 latent Usher syndrome, type 2a latent Usher syndrome, type 3 latent Usher syndrome, type 3-like latent Usher syndrome, atypical latent Usher syndrome, type 1 latent Usher syndrome, type 1b latent Usher syndrome, type 1d latent Usher syndrome, type 1f latent Usher syndrome, type 1J latent Usher syndrome, type 1k latent Usher syndrome, bigenic Usher syndrome due to CDH23 abnormality, bigenic Usher syndrome due to PCDH15 abnormality, Acadia latent Usher syndrome. Latent atypical Usher syndrome (USH3-like), Leber congenital amaurosis, latent Leber congenital amaurosis, dominant Leber congenital amaurosis, new-onset Leber congenital amaurosis, dominant Leber congenital amaurosis with pituitary dysfunction, latent Leber congenital amaurosis with myopathy, latent Leber congenital amaurosis with severe childhood retinal dystrophy, mitochondrial Leber hereditary optic neuropathy, Leber hereditary optic neuropathy, optic atrophy, latent optic atrophy, dominant optic atrophy, optic atrophy with ataxia, latent optic atrophy with ataxia, dominant optic atrophy with ataxia, latent optic atrophy with ataxia, latent optic atrophy with ataxia and 3-methylpentanoic aciduria, dominant optic atrophy with cataracts, ataxia and areflexia, Kaiser type dominant optic atrophy. Overt optic atrophy with sensorineural hearing loss, latent cerebellar degeneration with optic atrophy, optic atrophy with deafness-dystonia syndrome, X-linked optic atrophy with deafness-dystonia syndrome, retinal dystrophy, latent retinal dystrophy, overt retinal dystrophy, hereditary retinal dystrophy, early-onset latent retinal dystrophy, latent syndromic retinal dystrophy, latent non-syndromic retinal dystrophy, latent syndromic and non-syndromic retinal dystrophy, latent optic atrophy with retinal dystrophy, latent retinal dystrophy with obesity, latent retinal dystrophy with cerebellar dysplasia, syndromic latent optic atrophy with retinal dystrophy, overt retinal dystrophy with iris Defects, including ciliary spectrum disorders of retinal dystrophy, latent ciliary spectrum disorders of retinal dystrophy, overt ciliary spectrum disorders of retinal dystrophy, overt optic atrophy with neuropathy and myopathy, overt optic atrophy with intellectual disability and developmental delay, syndromic optic atrophy, nonsyndromic optic atrophy, latent nonsyndromic optic atrophy, overt nonsyndromic optic atrophy, latent syndromic optic atrophy, overt syndromic optic atrophy, Charcot-Marie-Tuss disease, latent Charcot-Marie-Tuss disease, overt Charcot-Marie-Tuss disease, benign punctate retinopathy, latent benign punctate retinopathy, overt benign punctate retinopathy, syndromic retinopathy, latent syndromic retinopathy.Overt syndrome retinopathy, Barten disease, latent Barten disease, overt Barten disease, latent Barten disease (neuronal ceroid lipofuscinosis type 3), juvenile latent Barten disease (neuronal ceroid lipofuscinosis type 3), neuronal ceroid lipofuscinosis, latent neuronal ceroid lipofuscinosis, latent neuronal ceroid lipofuscinosis type 1, overt neuronal ceroid lipofuscinosis, Staggart disease, latent Staggart disease, overt Staggart disease, juvenile Staggart disease, late-onset Staggart disease, Staggart disease-like macular dystrophy, latent Staggart disease-like macular dystrophy, overt Staggart disease-like macular dystrophy, macular dystrophy, latent macular dystrophy, early-onset macular dystrophy, adult-onset macular dystrophy. Early-onset latent macular dystrophy, adult-onset latent macular dystrophy, early-onset adult-onset latent macular dystrophy, juvenile latent macular dystrophy with sparse hairs, dominant macular dystrophy, late-onset dominant macular dystrophy, dominant macular dystrophy with lens suspensory ligament abnormalities, bull's-eye dominant macular dystrophy, butterfly-shaped dominant macular dystrophy, age-related dominant macular dystrophy, benign concentric ring dominant macular dystrophy, yolk-like latent macular dystrophy, yolk-like dominant macular dystrophy, atypical yolk-like dominant macular dystrophy, dominant adult-onset yolk-like macular dystrophy, Stagger's disease-like dominant macular dystrophy, Stagger's disease-type dominant macular dystrophy, North Carolina type dominant macular dystrophy, North Carolina Lennar-type dominant macular dystrophy, North Carolina-type dominant macular dystrophy with progressive sensorineural hearing loss, cystoid dominant macular dystrophy, Best type dominant macular dystrophy, occult macular dystrophy, latent occult macular dystrophy, dominant occult macular dystrophy, age-related familial macular dystrophy, X-linked atrophic macular dystrophy, latent X-linked atrophic macular dystrophy, dominant X-linked atrophic macular dystrophy, mitochondrial macular pattern dystrophy with type II diabetes and deafness, xanthomastia, latent xanthomastia, dominant xanthomastia, rod dystrophy, latent rod dystrophy, dominant rod dystrophy, cone dystrophy, latent... Cone dystrophy, manifest cone dystrophy, latent cone dystrophy with abnormal rod electroretinogram, early-onset latent cone dystrophy, late-onset latent cone dystrophy, type 1 cone dystrophy, X-linked type 1 cone dystrophy, type 2 cone dystrophy, type 2 progressive cone dystrophy, type 2 X-linked progressive cone dystrophy, delayed cone adaptation, delayed latent cone adaptation, delayed manifest cone adaptation, cone-rod dystrophy, latent cone-rod dystrophy, manifest cone-rod dystrophy, isolated cone-rod dystrophy, progressive cone-rod dystrophy, X-linked cone-rod dystrophy, X-linked progressive cone-rod dystrophy, progressive manifest cone-rod dystrophy.Cone-rod dystrophy with enamel hypoplasia syndrome, latent cone-rod dystrophy with enamel hypoplasia syndrome, manifest cone-rod dystrophy with enamel hypoplasia syndrome, latent cone-rod dystrophy with inner retinal lesions, latent cone-rod dystrophy with skeletal diseases, congenital syndromic non-progressive latent cone-rod dystrophy, latent cone-rod dystrophy with hearing loss, latent cone-rod dystrophy with psychomotor delay, latent cone with cone-rod dystrophy, cone-rod synaptic disorders, congenital cone-rod synaptic disorders, latent congenital cone-rod synaptic disorders, manifest congenital cone-rod synaptic disorders, rod-cone dystrophy, latent rod-cone dystrophy Hypotrophy, Dominant rod-cone dystrophy, Early-onset latent rod-cone dystrophy, Non-syndromic latent rod-cone dystrophy, Latent Newfoundland rod-cone dystrophy, Latent progressive cone dystrophy, Stickler syndrome, Dominant Stickler syndrome, Latent Stickler syndrome, Dominant Stickler syndrome type I, Dominant Stickler syndrome type II, Marshall syndrome, Dominant Marshall syndrome, Latent Marshall syndrome, Achromatopsia, Latent achromatopsia, Dominant achromatopsia, Latent complete achromatopsia, Latent incomplete achromatopsia, 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 Macular degeneration, drusen, latent drusen, dominant drusen, early-onset latent drusen, early-onset dominant drusen, macular drusen, dominant radiating macular drusen, pigmented paravenous choroidal retinal atrophy, latent pigmented paravenous choroidal retinal atrophy, dominant pigmented paravenous choroidal retinal atrophy, progressive bifocal choroidal retinal atrophy, Baldr-Biedel syndrome, latent Baldr-Biedel syndrome, dominant Baldr-Biedel syndrome, latent Baldr-Biedel syndrome with developmental abnormalities, retinal degeneration, latent retinal degeneration, dominant retinal degeneration, non-syndromic latent retinal degeneration, multifactorial honeycomb retinal degeneration, latent multifactorial honeycomb retinal degeneration, dominant multifactorial honeycomb retinal degeneration (Leventy) Ness disease), latent renal wasting disease with retinal degeneration, Alstrom syndrome, latent Alstrom syndrome, dominant Alstrom syndrome, Joubert syndrome, latent Joubert syndrome, dominant Joubert syndrome, Jobell syndrome, latent Jobell syndrome, dominant Jobell syndrome, X-linked Jobell syndrome, vitreoretinal degeneration, latent vitreoretinal degeneration, dominant vitreoretinal degeneration, snowflake vitreoretinal degeneration, snowflake dominant vitreoretinal degeneration, microstomia, latent microstomia, dominant microstomia, night blindness, stationary night blindness, congenital night blindness, congenital stationary night blindness, severe congenital stationary night blindness, latent congenital stationary night blindness, latent complete congenital stationary night blindness,Dominant congenital static night blindness, Nogarette type dominant congenital static night blindness, microstomia type latent congenital static night blindness, Riggs type latent congenital static night blindness, Schubert-Bornshain type latent congenital static night blindness, white spot fundus type latent congenital static night blindness, complete latent congenital static night blindness, X-linked congenital static night blindness, incomplete X-linked congenital static night blindness, retinal vascular disease, leukodystrophy, retinal vascular disease with leukodystrophy, latent retinal vascular disease with leukodystrophy, dominant retinal vascular disease with leukodystrophy, Ecardi-Gutier syndrome, Ecardi-Gutier syndrome type 1, latent Ecardi-Gutier syndrome. Gutierre syndrome type 1, dominant Ecardi-Gutierre syndrome type 1, frostbite-like lupus, latent frostbite-like lupus, dominant frostbite-like lupus, Martinic retinal dystrophy with retinitis pigmentosa, latent Martinic retinal dystrophy with retinitis pigmentosa, dominant Martinic retinal dystrophy with retinitis pigmentosa, spinocerebellar ataxia, latent spinocerebellar ataxia, dominant spinocerebellar ataxia, spinocerebellar ataxia with macular dystrophy, spinocerebellar ataxia with retinal degeneration, spinocerebellar ataxia with macular dystrophy or retinal degeneration, latent spinocerebellar ataxia with macular dystrophy or retinal degeneration, dominant spinocerebellar ataxia with macular dystrophy Or retinal degeneration, Wolfram syndrome, latent Wolfram syndrome, overt Wolfram syndrome, low-frequency sensorineural hearing loss, latent low-frequency sensorineural hearing loss, overt low-frequency sensorineural hearing loss, oculo-ear syndrome, latent oculo-ear syndrome, overt oculo-ear syndrome, latent kidney, skeletal and retinal abnormalities, latent abeloinemia, microcephaly, latent microcephaly, overt microcephaly, latent microcephaly with growth retinal disease, Biedi crystalline kerato-retinal dystrophy, latent pedunculated crystalline kerato-retinal dystrophy, overt pedunculated crystalline kerato-retinal dystrophy, Wagner's disease, erosive vitreoretinopathy, Wagner's disease with erosive vitreoretinopathy, latent Wolfram syndrome Wagner's disease with erosive vitreoretinopathy, overt Wagner's disease with erosive vitreoretinopathy, febrile seizures, latent febrile seizures, overt febrile seizures, overt / latent febrile seizures, choroidal dystrophy, latent choroidal dystrophy, overt choroidal dystrophy, central halo choroidal dystrophy, overt central halo choroidal dystrophy, latent central halo choroidal dystrophy, epiphyseal dysplasia, latent epiphyseal dysplasia, overt epiphyseal dysplasia, multiple epiphyseal dysplasia, latent multiple epiphyseal dysplasia, overt multiple epiphyseal dysplasia, ichthyosis, latent ichthyosis, overt ichthyosis, latent ichthyosis with quadriplegia, choroidal-retinal atrophy, bifocal choroidal-retinal atrophy.Progressive bifocal chorioretinal atrophy, latent progressive bifocal chorioretinal atrophy, overt progressive bifocal chorioretinal atrophy, Rife-Syme disease, latent Rife-Syme disease, overt Rife-Syme disease, adult latent Rife-Syme disease, infantile latent Rife-Syme disease, retinal-cone dystrophy, latent retinal-cone dystrophy, overt retinal-cone dystrophy, retinal-cone dystrophy type 1, latent retinal-cone dystrophy type 1, overt retinal-cone dystrophy type 1, blue-yellow color blindness, latent blue-yellow color blindness, overt blue-yellow color blindness, mucopolysaccharidosis, latent mucopolysaccharidosis, overt mucopolysaccharidosis, Pingerape achromatopsia, latent Pingerape achromatopsia, overt Pingerape achromatopsia. Krippel-Fair syndrome, latent Krippel-Fair syndrome, dominant Krippel-Fair syndrome, microphthalmia, latent microphthalmia, dominant microphthalmia, limb-girdle muscular dystrophy, latent limb-girdle muscular dystrophy, dominant limb-girdle muscular dystrophy, short-rib thoracic dysplasia, latent short-rib thoracic dysplasia, dominant short-rib thoracic dysplasia, latent short-rib thoracic dysplasia with polydactyly, latent short-rib thoracic dysplasia with retinal dystrophy, intellectual disability-trunk obesity-retinal dystrophy-micropenis (MORM) syndrome, latent MORM syndrome, dominant MORM syndrome, latent retinal delay with spasticity and retinal degeneration, Cockayne syndrome, latent Cockayne syndrome, dominant Cockayne syndrome, congenital retina Retinal detachment, latent nonsyndromic congenital retinal detachment, overt nonsyndromic congenital retinal detachment, hemolytic anemia, nonspherocytic hemolytic anemia, latent nonspherocytic hemolytic anemia, overt nonspherocytic hemolytic anemia, hereditary neuropathy, hereditary neuropathy (Russian type), latent hereditary neuropathy (Russian type), overt hereditary neuropathy (Russian type), choroidal sclerosis, latent choroidal sclerosis, overt choroidal sclerosis, retinopathy, latent retinopathy, overt retinopathy, overt and latent combined retinopathy, diffuse overt retinopathy, variant overt retinopathy, diffuse overt retinopathy with variant overt retinopathy, microcephaly, latent microcephaly, overt microcephaly, lymphoma Overt microcephaly due to lymphedema, overt microcephaly due to choroidal retinal disease, overt microcephaly due to lymphedema with choroidal retinal disease, choroidal retinal disease, latent choroidal retinal disease, overt choroidal retinal disease, choroidal retinal disease with microcephaly, latent choroidal retinal disease with microcephaly, overt choroidal retinal disease with microcephaly, renal defect syndrome, latent renal defect syndrome, overt renal defect syndrome, non-syndromic deafness, latent non-syndromic deafness, overt non-syndromic deafness, cycloplegic atrophy, latent cycloplegic atrophy, overt cycloplegic atrophy, cycloplegic choroidal atrophy, vitreoretinal disease, exudative vitreoretinal disease, familial exudative vitreoretinal disease.Latent familial exudative vitreoretinopathy, overt familial exudative vitreoretinopathy, overt familial exudative vitreoretinopathy with Kurtz's disease, neovascularization vitreoretinopathy, latent neovascularization vitreoretinopathy, overt neovascularization vitreoretinopathy, macular atrophy, latent macular atrophy, overt macular atrophy, Merkel syndrome, latent Merkel syndrome, overt Merkel syndrome, vitreoretinal-choroidal disease, latent vitreoretinal-choroidal disease, overt vitreoretinal-choroidal disease, yolk sac macular degeneration, latent yolk sac macular degeneration, overt yolk sac macular degeneration, high bone mass trait, latent high bone mass trait, overt high bone mass trait, osteoporosis-pseudoneurocyte glume Glioma syndrome, occult osteoporosis-pseudoglioma syndrome, overt osteoporosis-pseudoglioma syndrome, microphthalmia, occult microphthalmia, overt microphthalmia, retinal disease syndrome, occult retinal disease syndrome, overt retinal disease syndrome, microphthalmia with retinal disease syndrome, occult microphthalmia with retinal disease syndrome, overt microphthalmia with retinal disease syndrome, true microphthalmia, occult true microphthalmia, overt true microphthalmia, skeletal dysplasia, occult skeletal dysplasia, overt skeletal dysplasia, developmental disorder, osteoarthritis with syndromic disorders, cavitary optic disc abnormalities, occult cavitary optic disc abnormalities, overt cavitary optic disc abnormalities, white spot fundus, occult white spot fundus, overt white spot fundus, methylhydroxyl Valerateuria, latent mevalonuria, overt mevalonuria, high IgD syndrome, latent high IgD syndrome, overt high IgD syndrome, spastic paraplegia, latent spastic paraplegia, overt spastic paraplegia, latent spastic paraplegia with neuropathy, latent spastic paraplegia with optic atrophy, latent spastic paraplegia with optic atrophy (dementia) due to neuropathy, latent dementia, overt dementia, familial overt dementia, retinoblastoma, latent retinoblastoma, overt retinoblastoma, germ cell retinoblastoma, somatic cell retinoblastoma, overt germ cell or somatic cell retinoblastoma, retinaculum, benign retinaculum, pineal tumor, osteosarcoma, rod monochromatic vision, latent rod monochromatic vision Visual acuity, dominant rod monochromatic vision, total color blindness, latent total color blindness, dominant total color blindness, rod total color blindness, rod latent total color blindness, rod dominant total color blindness, latent rod monochromatic vision or total color blindness, figure-like malnutrition, latent figure-like malnutrition, dominant figure-like malnutrition, S-cone syndrome, enhanced S-cone syndrome (ESC), latent ESC, dominant ESC, Goldman-Favre syndrome, latent Goldman-Favre syndrome, dominant Goldman-Favre syndrome, Portinia type malnutrition, latent Portinia type malnutrition, dominant Portinia type malnutrition, white spot retinal degeneration, latent white spot retinal degeneration, dominant white spot retinal degeneration, mucosal storage disease type IIIγ, latent mucosal storage disease type IIIγ,Dominant mucinous storage disease type IIIγ, Meinzel-Saldino syndrome, latent Meinzel-Saldino syndrome, dominant Meinzel-Saldino syndrome, elastic pseudoxanthoma, latent elastic pseudoxanthoma, dominant elastic pseudoxanthoma, Knobloch syndrome, latent Knobloch syndrome, dominant Knobloch syndrome, foveal dysplasia, latent foveal dysplasia, dominant foveal dysplasia, anterior segment dysplas...

Claims

1. A recombinant herpesvirus genome, said recombinant herpesvirus genome comprising one or more polynucleotides encoding polypeptides.

2. The recombinant herpesvirus genome according to claim 1, wherein the recombinant herpesvirus genome is capable of replication.

3. The recombinant herpesvirus genome according to claim 1, wherein the recombinant herpesvirus genome is replication-defective.

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

5. The recombinant herpesvirus genome according to any one of claims 1-4, wherein the recombinant herpesvirus genome is a recombinant herpes simplex virus genome.

6. The recombinant herpesvirus genome according to claim 5, wherein 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 derivative thereof.

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

8. The recombinant herpesvirus genome according to any one of claims 4-7, wherein the recombinant herpes simplex virus genome has been engineered to reduce or eliminate the expression of one or more virulent herpes simplex virus genes.

9. The recombinant herpesvirus genome according to any one of claims 4-8, wherein the recombinant herpes simplex virus genome contains inactivating mutations.

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

11. The recombinant herpesvirus genome of 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 Infecting Cell Protein (ICP) 0, ICP4, ICP22, ICP27, ICP47, thymidine kinase (tk), long unique region (UL) 41 and UL55.

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

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

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

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

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

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

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

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

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

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

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

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

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

26. The recombinant herpesvirus genome according to any one of claims 4-25, 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 1-26, wherein the polypeptide is a human polypeptide.

28. The recombinant herpesvirus genome according to any one of claims 1-27, wherein the polypeptide is selected from the following: protein 11 containing the sterile α-motif domain, renal cyst protein 4, espin, nicotinamide / nicotinic acid mononucleotide adenosyltransferase 1, mitochondrial fusion protein 2, endoplasmic reticulum membrane protein complex subunit 1, group V phospholipase A2, dehydrogenase-1,2-diphosphate synthase complex subunit, palmitoyl protein thioesterase 1, very long chain fatty acid elongation protein 1, protein O-linked mannose β-1,2-N-acetylglucosamine aminotransferase 1, retinoid isomerase, retinal-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-regulating autophagy regulator protein 2, U4 / U6 small nucleoribonucleoprotein Prp 3, α-sulfonamide protein 1, and acetyl-2-aminophenol protein 2. Peptide, serotonin 4A, cyclic AMP-dependent transcription factor ATF-6α, hemicentin-1, complement factor H, crumbs protein homolog 1, adiponectin receptor protein 1, RD3 protein, serine / threonine protein kinase Nek2, feline leukemia virus C subset receptor-associated protein 1, Usherin, serologically defined colon cancer antigen 8, olfactory receptor 2W3, NBAS subunit of NRZ tethering complex, cytoplasmic carboxypeptidase-like protein 5, zinc finger protein 513, flagellated intratransporter protein 172 homolog, photoreceptor ciliary actin regulator, EGF-containing fibula protein-like extracellular matrix protein 1 / TLE family member 5, FAM161A protein, planar cell polar effector protein fritz homolog containing WD repeat sequence, centrosome-associated protein ALMS1, U5 small nucleoribonucleoprotein 200 kDa helicase, metallotransferase CNNM4, cyclic nucleotide-gated cation channel α-3, renal cystin 1, tyrosine protein kinase Mer, Baldr-Biedel syndrome-associated protein 5, ceramide kinase-like protein, neurogenic differentiation factor 1, transmembrane protein 237, inward rectifier potassium channel 13, S-repressor protein, secretory phosphoprotein 24, mitochondrial CCA tRNA nucleotide transferase 1, sodium bicarbonate cotransporter 3, leucine zipper transcription factor-like protein 1, guanine nucleotide-binding protein G(t) subunit α-1, 3' repair exonuclease 1, MAP kinase-activated protein kinase 3, ataxia protein 7, vitamin K-dependent protein S, ADP riboylation factor-like protein 6, photoreceptor interstitial proteoglycan 2, IQ-containing calmodulin-binding motif protein 1, rhodopsin, renal cystin 3, Clarin-1, possible cation amino acid transporter / solute carrier family 7 member 14, phosphocholine cytyltransferase A, 19 kDa centrosomal protein, rod cGMP-specific 3',5'-cyclic nucleotide phosphodiesterase subunit β, Wolframin, homeobox protein HMX1, Ras-associated protein Rab-28, and protein 2A containing a coiled-coil C2 domain.Prominin-1, adhesion G protein-coupled receptor A3, protein 1 containing death domain, protein 19 containing WD repeat sequence, cGMP-gated cation channel α-1, protein 2 containing CDGSH iron-sulfur domain, large subunit of microsomal triglyceride transporter, protein 3 containing leucine-rich repeat sequence, immunoglobulin-like domain and transmembrane domain, Baldr-Biedel syndrome-associated protein 7, Baldr-Biedel syndrome-associated protein 12, protein 8 containing major facilitated superfamily domain, serine / threonine protein kinase PLK, lecithin retinyl acyltransferase, Toll-like receptor, cytochrome P450. 4V2, spliceosome-associated protein CWC27 homolog, centrosome protein POC5, multifunctional proteoglycan core protein, adhesion G protein-coupled receptor V1, COUP transcription factor 1, mitochondrial outer membrane protein SLC25A46, catalin α-1, cytoplasmic histidine-tRNA ligase, rod cGMP-specific 3',5'-cyclic nucleotide phosphodiesterase subunit α, metabolite glutamate receptor 6, serine / threonine protein kinase MAK, complement C2, complement factor B, Tubby-associated protein 1, guanylate cyclase activator 1, guanylate cyclase activator 2, peripheral protein 2, photoreceptor intercellular matrix proteoglycan 1, eyes Shut protein homolog, collagen α-1 (IX) chain, regulatory synaptic exocytogenin 1, Lebercilin, very long chain fatty acid elongation protein 4, PR domain zinc finger protein 13, mitochondrial reticulin 4 interacting protein 1, Jouberin, peroxisome guide signal 2 receptor, CCR4-NOT transcription complex subunit 9, aryl hydrocarbon receptor, Kelch-like protein 7, retinitis pigmentosa type 9 protein, PTHB1 protein, peroxisome ATPase PEX1, tetratransmembrane protein 12, inosine-5'-monophosphate dehydrogenase 1, short-wavelength sensitive opsin 1, UPF0606 protein KIAA1549, retinitis pigmentosa type 1 protein-like 1 protein, protein containing detegrin metalloproteinase domain 9, heparin-α-aminoglycine N-acetyltransferase, oxygen regulator protein 1, α-tocopherol transporter, centrosome and spindle polar-associated protein 1, mitochondrial activator protein-like 120 kDa protein, peroxisome biogenesis factor 2, cyclic nucleotide-gated cation channel β-3, ciliary and flagella-associated protein 418, growth differentiation factor 6, regulatory synaptic exocytogenin 2, voltage-gated potassium channel subfamily V member 2, E3 ubiquitin-protein ligases Topors, 78 kDa centrosomal protein, Inversin, U4 / U6 small nucleoribonucleoprotein Prp4, Whirlin, E3 ubiquitin-protein ligase TRIM32, Toll-like receptor 4, cytoplasmic dynein 2 intermediate chain 2, programmed cell death protein 2, exosome complex component RRP4, type IV phosphatidylinositol polyphosphate-5-phosphatasePeroxisome phytyl-CoA dioxygenase, 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, kinin-like protein KIF11, retinol-binding protein 4, cone cGMP-specific 3',5'-cyclic nucleotide phosphodiesterase subunit α, pairing box protein Pax-2, PDZ-domain-containing protein 7, ADP-ribosylation factor-like protein 3, BBSome interacting protein 1, age-related macular degeneration susceptibility protein 2, serine protease HTRA1, mitochondrial ornithine aminotransferase, zinc finger protein 408, Tubby Protein homologs, transcription enhancer TEF-1, Harmonin, transmembrane protein 216, Bestrophin-1, isaspartic peptidase / L-asparaginase, rod outer membrane protein 1, Baldr-Biedel syndrome-associated protein 1, calcium-binding protein 4, low-density lipoprotein receptor-associated protein 5, calpain 5, unconventional myosin VIIa, transmembrane protein 126A, coilin 4, cytoplasmic dysin 2 light intermediate chain 1, 164kDa centrosome protein, complement C1q tumor necrosis factor-associated protein 5, membrane coil-associated protein, voltage-dependent calcium channel subunits α-2 / δ-4, guanine nucleotide-binding protein G(I) / G(S) / G(T) subunits β-3, cone rhodopsin-sensitive cGMP 3',5'-cyclic nucleotide phosphodiesterase subunit γ, collagen α-1(II) chain, matrix metalloproteinase 19, retinol dehydrogenase 5, T complex protein 1 subunit β, Baldr-Biedel syndrome-associated protein 10, 290 kDa centrosome protein, POC1 centriolein homolog B, mevalonate kinase, flagellar transporter 81 homolog, rescue mitochondrial translational releasing factor, integrated membrane protein 2B, retinoblastoma-associated protein, protein containing RCC1 and BTB domains 1, rhodopsin kinase GRK1, X-linked retinitis pigmentosa GTPase regulatory factor interacting protein 1, neuroretinal-specific leucine zipper protein, homologous box protein OTX2, retinol dehydrogenase 11, retinol dehydrogenase 12, microtubule polyglutamylase TTLL5, spermatogenesis-associated protein 7, triglycerides Angular tetrapeptide repeat protein 8, fibula protein 5, transient receptor potential cation channel subfamily M member 1, γ-tubulin complex component 4, sodium / potassium / calcium exchanger 1, photoreceptor-specific nuclear receptor, Baldr-Biedel syndrome-associated protein 4, calcium and integrin binding family member 2, retinaldehyde binding protein 1, N-acetylglucosamine-1-phosphotransferase subunit γ, flagellar transporter 140 homolog, clustering-associated protein 1, ATP-binding box subfamily C member 6, ketimine reductase μ-crystal protein, battenin, zinc finger protein 423, fantom protein,Balder-Biedel syndrome-associated protein 2, ADP-ribosylation factor-like protein 2 binding protein, cyclic nucleotide-gated cation channel β-1, cadherin 3, pre-mRNA splicing factor ATP-dependent RNA helicase PRP16, platelet-reactive protein motif detegrin and metalloproteinase 18, solute carrier family 38 member 8, retinal guanylate cyclase 1, pre-mRNA processing splicing factor 8, aryl hydrocarbon interacting protein-like 1 protein, membrane-associated phosphatidylinositol transporter 3, unc-119 protein homolog A, possible G protein-coupled receptor 179, Tectonic-like complex member MKS1, carbonic anhydrase 4, G protein signaling regulator 9, arylsulfatase G, pre-mRNA splicing regulator USH1G, photoreceptor disk component PRCD, myofascitis 2, rod rhodopsin-sensitive cGMP 3',5'-cyclic nucleotide phosphodiesterase subunit γ, laminin subunit α-1, AFG3-like protein 2, cone-rod homologous box protein, receptor expression enhancer protein 6, retinal and anterior nerve fold homologous box protein 2, complement C3, Rho guanine nucleotide exchange factor 18, protein containing potato glycoprotein-like phospholipase domain 6, G protein signaling regulator 9 binding protein, optic atrophy protein 3, U4 / U6 small nucleoribonucleoprotein Prp31, mitochondrial isocitrate dehydrogenase [NAD] subunit β Mitochondrial pantothenic acid kinase 2, jagged-1 protein, molecular chaperone MKKS, centrosome protein kizuna, lysophosphatidylserine lipase ABHD12, kinin-like protein KIF3B, centrosome-associated protein CEP250, pre-mRNA processing factor 6, ciliary and flagellate-associated protein 410, activator 1-like protein, inhibitor of metalloproteinases 3, flagellated intratransporter 27 homolog, peronein 1, MIEF1 upstream open reading frame protein, mitochondrial aconitine hydratase, γ- Microtubule complex component 6, centrioles and centriole satellite proteins, retinal schistosome protein, XRP2 protein, dystrophin, X-linked retinitis pigmentosa GTPase regulator, night blindness protein, Xaa-Pro dipeptidase, Norrin, voltage-dependent L-type calcium channel subunit α-1F, phosphoglycerate kinase 1, Rab protein geranyl-geranyl transferase component A1, mitochondrial ingress membrane translocase subunit Tim8A, phosphoribosylpyrophosphate kinase 1, long-wavelength sensitive opsin 1, medium-wavelength sensitive opsin Opsin 1, short-wavelength sensitive opsin 1, mitochondrial transcription factor A, 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 bMitochondrial leucine-tRNA ligase, mitochondrial undifferentiated glutamyl-tRNA synthetase EARS2, lysine-tRNA ligase, mitochondrial histidine-tRNA ligase, mitochondrial serine-tRNA ligase, mitochondrial proline-tRNA ligase, cyanocobalamin reductase / alkylcobamamin dealkylase, POU domain class 3 transcription factor 4, ribosomal protein S6 kinase α-6, ciliogenesis and planar cell polar effector factor 1, Meckelin, TRAF3 interacting protein 1, flagellated transporter 74 homolog, endoplasmic reticulum S-phase cycle protein A-related protein, sodium ion channel and clathrin linker factor 1, TALPID3 protein, Tectonic-2, ADP ribosylation factor-like protein 13B, B9 domain-containing protein 1, B9 domain-containing protein 2, C2 domain-containing protein 3, 41 kDa centrosome protein, 104 kDa centrosome protein, 120 kDa centrosome protein, flagellated transporter 172 homolog, chevone-interacting protein, kinin-like protein KIF7, rod rhodopsin-sensitive cGMP 3',5'-cyclic nucleotide phosphodiesterase subunit δ, Tectonic-1, Tectonic-3, transmembrane protein 107, transmembrane protein 138, transmembrane protein 231, triangular tetrapeptide 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 binding homologous box protein 1, type II keratin Hb3, type I cytoskeleton keratin 12, transforming growth factor β-inducible protein ig-h3, tumor-associated calcium signaling protein 2, carbohydrate sulfonyltransferase 6, coagulant protein, protein containing UbiA isopentenyltransferase domain 1, core proteoglycan, 1-phosphatidylinositol 3-phosphate 5-kinase, transcription factor Ovo-like 2 protein and granular head-like protein 2 homolog.

29. The recombinant herpesvirus genome of 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 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 1-29, wherein the polypeptide is β-nerve growth factor, retinal-specific phospholipid transporter ATPase, or 290 kDa centrosome protein.

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

32. The recombinant herpesvirus genome of 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 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 claim 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 the amino acid sequence of SEQ ID NO:

740.

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

35. The recombinant herpesvirus genome of claim 34, wherein the retinal-specific phospholipid transporter 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 the amino acid sequence of SEQ ID NO:

33.

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

37. The recombinant herpesvirus genome of claim 36, wherein the 290 kDa 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 the amino acid sequence of SEQ ID NO:

219.

38. The recombinant herpesvirus genome according to any one of claims 1-37, wherein the recombinant herpesvirus genome has reduced cytotoxicity when introduced into target cells 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 38-40, wherein the target cells are corneal epithelial cells, rod cells, cone cells, photoreceptors, retinal pigment epithelial cells, retinal ganglion cells, bipolar cells, horizontal cells, Miller cells, or cells without long processes.

42. A herpesvirus comprising a recombinant herpesvirus genome according to any one of claims 1-41.

43. The herpesvirus of claim 42, wherein the herpesvirus is capable of replication.

44. The herpesvirus of claim 42, wherein the herpesvirus is a replication-defective type.

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

46. ​​The herpesvirus according to any one of claims 42-45, wherein the herpesvirus is selected from herpes simplex virus, varicella-zoster virus, human cytomegalovirus, herpesvirus 6A, herpesvirus 6B, herpesvirus 7, EB virus, and Kaposi's sarcoma-associated herpesvirus.

47. The herpesvirus according to any one of claims 42-46, wherein the herpesvirus is herpes simplex virus.

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 46-48, 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 1-41 or a herpesvirus according to any one of claims 42-49, and a pharmaceutically acceptable excipient.

51. The pharmaceutical composition of claim 50, wherein the pharmaceutical composition is suitable for ocular, subretinal, intraocular, vitreous, anterior chamber, external, subcutaneous, subconjunctival, subfascial, subcapsular, anterior chamber, retrobulbar, systemic, extra-gastric, perioral, near the sclera, anterior near the sclera, posterior near the sclera, oral, perioral, or choroidal application.

52. The pharmaceutical composition according to claim 50 or claim 51, wherein the pharmaceutical composition is suitable for intraocular, subretinal, vitreous, anterior chamber, choroidal, or topical application.

53. The pharmaceutical composition according to any one of claims 50-52, wherein the pharmaceutical composition is suitable for application to the choroid or for external use.

54. The pharmaceutical composition according to any one of claims 50-53, wherein the pharmaceutical composition is suitable for application onto the choroid.

55. The pharmaceutical composition according to any one of claims 50-53, wherein the pharmaceutical composition is suitable for external application.

56. The pharmaceutical composition according to any one of claims 50-55, wherein the pharmaceutical composition is suitable for use as eye drops, ointment, paste, cream, suspension, emulsion, fat ointment, gel, bioadhesive gel, powder, lotion, solution, spray, or any combination thereof.

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

58. The herpesvirus according to any one of claims 42-49 or the pharmaceutical composition according to any one of claims 50-57, for use as a pharmaceutical agent.

59. The herpesvirus according to any one of claims 42-49 or the pharmaceutical composition according to any one of claims 50-57, for use in a therapeutic manner, optionally wherein the herpesvirus or the pharmaceutical composition is used in the treatment of an eye condition or disease, and optionally wherein the eye condition or disease is selected from retinitis pigmentosa, latent retinitis pigmentosa, severe latent retinitis pigmentosa, overt retinitis pigmentosa, overt retinitis pigmentosa with choroidal involvement, latent retinitis pigmentosa with para-arteriolar retinopathy (PPRPE), latent retinitis pigmentosa with posterior column ataxia (PCARP), latent retinitis pigmentosa with microcytic polycythemia, and syndromic latent retinitis pigmentosa. Degenerative, latent syndromic retinitis pigmentosa, non-syndromic latent retinitis pigmentosa, non-syndromic overt retinitis pigmentosa, syndromic overt retinitis pigmentosa, juvenile latent retinitis pigmentosa, latent retinitis pigmentosa with intellectual disability, latent retinitis pigmentosa with macular degeneration, severe early-onset latent retinitis pigmentosa, latent retinitis pigmentosa with skeletal abnormalities, latent retinitis pigmentosa with skeletal deformities, overt retinitis pigmentosa with sensorineural hearing loss, latent retinitis pigmentosa with hearing loss, latent retinitis pigmentosa with hearing loss and other impairments, latent retinitis pigmentosa with vitreous changes, early-onset latent retinitis pigmentosa with macular defects, X-linked retinitis pigmentosa 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, Bald-Biedel syndrome-like retinitis pigmentosa, Bald-Biedel syndrome-like recessive retinitis pigmentosa, bigenic retinitis pigmentosa, bigenic retinitis pigmentosa due to abnormality of outer retinal membrane protein 1, bigenic retinitis pigmentosa due to abnormality of PRPH2, recessive retinitis pigmentosa with early macular involvement, recessive deafness without retinitis pigmentosa, recessive congenital deafness without retinitis pigmentosa, recessive retinitis pigmentosa with recessive ataxia, and recessive retinitis pigmentosa. Sexually associated 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 deafness and neurological abnormalities, autosomal dominant retinitis pigmentosa, non-syndromic 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, Sinier-Lacken syndrome, recessive Sinier-Lacken syndrome, dominant Sinier-Lacken syndrome,Kidney wasting disease, latent kidney wasting disease, overt kidney wasting disease, juvenile latent kidney wasting disease, ciliopathy-associated latent kidney wasting disease, juvenile kidney wasting disease, juvenile latent kidney wasting disease, juvenile overt kidney wasting disease, Usher syndrome, Usher syndrome type I, Usher syndrome type II, Usher syndrome type III, latent Usher syndrome, atypical latent Usher syndrome, overt Usher syndrome, type 2 latent Usher syndrome, type 2a latent Usher syndrome, type 3 latent Usher syndrome, type 3-like latent Usher syndrome, atypical latent Usher syndrome, type 1 latent Usher syndrome, type 1b latent Usher syndrome, type 1d latent Usher syndrome, type 1f latent Usher syndrome, type 1J latent Usher syndrome, type 1k latent Usher syndrome, due to Bigenic Usher syndrome due to CDH23 abnormality, Bigenic Usher syndrome due to PCDH15 abnormality, Acadia recessive Usher syndrome, Recessive atypical Usher syndrome (USH3-like), Leber congenital amaurosis, Recessive Leber congenital amaurosis, Dominant Leber congenital amaurosis, New-onset Leber congenital amaurosis, Dominant Leber congenital amaurosis with 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 atrophy, Recessive optic atrophy, Dominant optic atrophy, Optic atrophy with ataxia, Recessive optic atrophy with ataxia, Dominant optic atrophy with ataxia, Recessive optic atrophy Accompanied by ataxia and 3-methylpentanoic aciduria, overt optic atrophy with cataracts, ataxia and areflexia, Kaiser type overt optic atrophy, overt optic atrophy with sensorineural hearing loss, latent cerebellar degeneration with optic atrophy, optic atrophy with deafness-dystonia syndrome, X-linked optic atrophy with deafness-dystonia syndrome, retinal dystrophy, latent retinal dystrophy, overt retinal dystrophy, hereditary retinal dystrophy, early-onset latent retinal dystrophy, latent syndromic retinal dystrophy, latent nonsyndromic retinal dystrophy, latent syndromic and nonsyndromic retinal dystrophy, latent optic atrophy with retinal dystrophy, latent retinal dystrophy with obesity. Latent retinal dystrophy with cerebellar dysplasia; Syndrome of latent optic atrophy with retinal dystrophy; Overt retinal dystrophy with iris defects; Ciliary spectrum disorders including retinal dystrophy; Latent ciliary spectrum disorders including retinal dystrophy; Overt ciliary spectrum disorders including retinal dystrophy; Overt optic atrophy with neuropathy and myopathy; Overt optic atrophy with intellectual disability and developmental delay; Syndrome of optic atrophy; Non-syndrome of optic atrophy; Latent non-syndrome of optic atrophy; Overt non-syndrome of optic atrophy; Latent syndrome of optic atrophy; Overt syndrome of optic atrophy; Charcot-Marie-Tuss disease; Latent Charcot-Marie-Tuss disease; Overt Charcot-Marie-Tuss disease.Benign punctate retinopathy, latent benign punctate retinopathy, overt benign punctate retinopathy, syndromic retinopathy, latent syndromic retinopathy, overt syndromic retinopathy, Barten disease, latent Barten disease, overt Barten disease, latent Barten disease (neuronal ceroid lipofuscinosis type 3), juvenile latent Barten disease (neuronal ceroid lipofuscinosis type 3), neuronal ceroid lipofuscinosis, latent neuronal ceroid lipofuscinosis, latent neuronal ceroid lipofuscinosis type 1, overt neuronal ceroid lipofuscinosis, Staggart disease, latent Staggart disease, overt Staggart disease, juvenile Staggart disease, late-onset Staggart disease, Staggart disease-like macular dystrophy, latent Staggart disease-like macular dystrophy, overt Staggart's disease-like macular dystrophy, macular dystrophy, latent macular dystrophy, early-onset macular dystrophy, adult-onset macular dystrophy, early-onset latent macular dystrophy, adult-onset latent macular dystrophy, early-onset adult-onset latent macular dystrophy, juvenile latent macular dystrophy with sparse hairs, dominant macular dystrophy, late-onset dominant macular dystrophy, dominant macular dystrophy with lens suspensory ligament abnormalities, bull's-eye dominant macular dystrophy, butterfly-shaped dominant macular dystrophy, age-related dominant macular dystrophy, benign concentric ring dominant macular dystrophy, yolk-like latent macular dystrophy, yolk-like dominant macular dystrophy, atypical yolk-like dominant macular dystrophy, dominant adult-onset yolk-like macular dystrophy. Staggart's disease-like dominant macular dystrophy, Staggart's disease-type dominant macular dystrophy, North Carolina-type dominant macular dystrophy, North Carolina-type dominant macular dystrophy, North Carolina-type dominant macular dystrophy with progressive sensorineural hearing loss, cystoid dominant macular dystrophy, Best type dominant macular dystrophy, occult macular dystrophy, latent occult macular dystrophy, dominant occult macular dystrophy, age-related familial macular dystrophy, X-linked atrophic macular dystrophy, latent X-linked atrophic macular dystrophy, dominant X-linked atrophic macular dystrophy, mitochondrial macular pattern dystrophy with type II diabetes and deafness, xanthomastia, latent xanthomastia. Dot syndrome, manifest yellow macular degeneration, rod dystrophy, latent rod dystrophy, manifest rod dystrophy, cone dystrophy, latent cone dystrophy, manifest cone dystrophy, latent cone dystrophy with rod electroretinogram abnormalities, early-onset latent cone dystrophy, late-onset latent cone dystrophy, cone dystrophy type 1, X-linked cone dystrophy type 1, cone dystrophy type 2, progressive cone dystrophy type 2, X-linked progressive cone dystrophy type 2, delayed cone adaptation, delayed latent cone adaptation, delayed manifest cone adaptation, cone-rod dystrophy, latent cone-rod dystrophy, manifest 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 with enamel hypoplasia syndrome, latent cone-rod dystrophy with enamel hypoplasia syndrome, dominant cone-rod dystrophy with enamel hypoplasia syndrome, latent cone-rod dystrophy with inner retinal lesions, latent cone-rod dystrophy with skeletal diseases, congenital syndromic non-progressive latent cone-rod dystrophy, latent cone-rod dystrophy with hearing loss, latent cone-rod dystrophy with psychomotor delay, latent cone with cone-rod dystrophy, cone-rod synaptic diseases, congenital cone-rod synaptic diseases, latent Congenital cone-rod synaptic disorders, dominant congenital cone-rod synaptic disorders, rod-cone dystrophy, latent rod-cone dystrophy, dominant rod-cone dystrophy, early-onset latent rod-cone dystrophy, non-syndromic latent rod-cone dystrophy, latent Newfoundland type rod-cone dystrophy, latent progressive cone dystrophy, Stickler syndrome, dominant Stickler syndrome, latent Stickler syndrome, dominant Stickler syndrome type I, dominant Stickler syndrome type II, Marshall syndrome, dominant Marshall syndrome, latent Marshall syndrome, achromatopsia, latent achromatopsia, dominant achromatopsia, latent complete achromatopsia, latent incomplete achromatopsia, macular degeneration, age-related macular degeneration Age-related macular degeneration (AMD) with complex etiologies, including isolated AMD, wet AMD, dry AMD, drusen, latent drusen, overt drusen, early-onset latent drusen, early-onset overt drusen, macular drusen, overt radiating macular drusen, pigmented paravenous choroidal retinal atrophy, latent pigmented paravenous choroidal retinal atrophy, overt pigmented paravenous choroidal retinal atrophy, progressive bifocal choroidal retinal atrophy, Balder-Biedel syndrome, latent Balder-Biedel syndrome, overt Balder-Biedel syndrome, latent Balder-Biedel syndrome with developmental abnormalities, retinal degeneration, latent retinal degeneration, overt retinal degeneration, and non-syndromic retinal degeneration. Latent retinal degeneration, multifactorial celluloid retinal degeneration, latent multifactorial celluloid retinal degeneration, overt multifactorial celluloid retinal degeneration (Leventinese disease), latent renal wasting disease with retinal degeneration, Alstrom syndrome, latent Alstrom syndrome, overt Alstrom syndrome, Joubert syndrome, latent Joubert syndrome, overt Joubert syndrome, Jobell syndrome, latent Jobell syndrome, overt Jobell syndrome, X-linked Jobell syndrome, vitreoretinal degeneration, latent vitreoretinal degeneration, overt vitreoretinal degeneration, snowflake vitreoretinal degeneration, snowflake overt vitreoretinal degeneration, microstomia, latent microstomia, overt microstomia, night blindness, stationary night blindness, congenital night blindness.Congenital static night blindness, severe congenital static night blindness, latent congenital static night blindness, latent complete congenital static night blindness, manifest congenital static night blindness, Nogarette type manifest congenital static night blindness, microstomia type latent congenital static night blindness, Riggs type latent congenital static night blindness, Schubert-Bornshain type latent congenital static night blindness, white spot fundus type latent congenital static night blindness, complete latent congenital static night blindness, X-linked congenital static night blindness, incomplete X-linked congenital static night blindness, retinal vascular disease, leukodystrophy, retinal vascular disease with leukodystrophy, latent retinal vascular disease with leukodystrophy, manifest retinal retina Membranous vascular disease with leukodystrophy, Ecardi-Gutier syndrome, Ecardi-Gutier syndrome type 1, latent Ecardi-Gutier syndrome type 1, overt Ecardi-Gutier syndrome type 1, frostbite-like lupus, latent frostbite-like lupus, overt frostbite-like lupus, Martinic retinal dystrophy with retinitis pigmentosa, latent Martinic retinal dystrophy with retinitis pigmentosa, overt Martinic retinal dystrophy with retinitis pigmentosa, spinocerebellar ataxia, latent spinocerebellar ataxia, overt spinocerebellar ataxia, spinocerebellar ataxia with macular dystrophy, spinocerebellar ataxia with retinal degeneration, spinocerebellar ataxia with macular dystrophy or retinal degeneration. Sexual, latent spinocerebellar ataxia with macular dystrophy or retinal degeneration, overt spinocerebellar ataxia with macular dystrophy or retinal degeneration, Wolfram syndrome, latent Wolfram syndrome, overt Wolfram syndrome, low-frequency sensorineural hearing loss, latent low-frequency sensorineural hearing loss, overt low-frequency sensorineural hearing loss, oculo-otonic syndrome, latent oculo-otonic syndrome, overt oculo-otonic syndrome, latent kidney, skeletal and retinal abnormalities, latent abeta-lipoproteinemia, microcephaly, latent microcephaly, overt microcephaly, latent microcephaly with growth retinal disease, Biertial crystalline kerato-retinal dystrophy, latent pedunculated crystalline kerato-retinal dystrophy, overt pedunculated crystalline kerato-retinal dystrophy Membrane dystrophy, Wagner's disease, erosive vitreoretinopathy, Wagner's disease with erosive vitreoretinopathy, latent Wagner's disease with erosive vitreoretinopathy, overt Wagner's disease with erosive vitreoretinopathy, febrile seizures, latent febrile seizures, overt febrile seizures, overt / latent febrile seizures, choroidal dystrophy, latent choroidal dystrophy, overt choroidal dystrophy, central halo choroidal dystrophy, overt central halo choroidal dystrophy, latent central halo choroidal dystrophy, epiphyseal dysplasia, latent epiphyseal dysplasia, overt epiphyseal dysplasia, multiple epiphyseal dysplasia, latent multiple epiphyseal dysplasia, overt multiple epiphyseal dysplasia, ichthyosis, latent ichthyosisOvert ichthyosis, latent ichthyosis with quadriplegia and slowed retinal function, choroidal retinal atrophy, bifocal choroidal retinal atrophy, progressive bifocal choroidal retinal atrophy, latent progressive bifocal choroidal retinal atrophy, overt progressive bifocal choroidal retinal atrophy, Rife's disease, latent Rife's disease, overt Rife's disease, adult latent Rife's disease, infantile latent Rife's disease, retinal-cone dystrophy, latent retinal-cone dystrophy, overt retinal-cone dystrophy, retinal-cone dystrophy type 1, latent retinal-cone dystrophy type 1, overt retinal-cone dystrophy type 1, blue-yellow color blindness, latent blue-yellow color blindness, overt blue-yellow color blindness, mucopolysaccharidosis, latent mucopolysaccharidosis. Dominant mucopolysaccharidosis, Pingrapp achromatopsia, Latent Pingrapp achromatopsia, Dominant Pingrapp achromatopsia, Krippel-Fair syndrome, Latent Krippel-Fair syndrome, Dominant Krippel-Fair syndrome, Microphthalmia, Latent Microphthalmia, Dominant Microphthalmia, Limb-girdle muscular dystrophy, Latent Limb-girdle muscular dystrophy, Dominant Limb-girdle muscular dystrophy, Short-rib thoracic dysplasia, Latent Short-rib thoracic dysplasia, Dominant Short-rib thoracic dysplasia, Latent Short-rib thoracic dysplasia with Polydactyly, Latent Short-rib thoracic dysplasia with Retinal Dystrophy, Mental Disability-Trunk Obesity-Retinal Dystrophy-Micropenis (MORM) syndrome, Latent MORM syndrome, Dominant MORM syndrome, Spasticity with Retinal Latent delay in membranous degeneration, Cockayne syndrome, latent Cockayne syndrome, dominant Cockayne syndrome, congenital retinal detachment, latent non-syndromic congenital retinal detachment, dominant non-syndromic congenital retinal detachment, hemolytic anemia, non-spherocytic hemolytic anemia, latent non-spherocytic hemolytic anemia, dominant non-spherocytic hemolytic anemia, hereditary neuropathy, hereditary neuropathy (Russian type), latent hereditary neuropathy (Russian type), dominant hereditary neuropathy (Russian type), choroidal sclerosis, latent choroidal sclerosis, dominant choroidal sclerosis, retinopathy, latent retinopathy, dominant retinopathy, combined dominant and latent retinopathy, diffuse dominant retinopathy, variant dominant retinopathy. Lesions, diffuse retinopathy with variants, microcephaly, latent microcephaly, manifest microcephaly, manifest microcephaly with lymphedema, manifest microcephaly with choroidal retinal disease, manifest microcephaly with lymphedema and choroidal retinal disease, choroidal retinal disease, latent choroidal retinal disease, manifest choroidal retinal disease, choroidal retinal disease with microcephaly, latent choroidal retinal disease with microcephaly, manifest choroidal retinal disease with microcephaly, renal defect syndrome, latent renal defect syndrome, manifest renal defect syndrome, non-syndromic deafness, latent non-syndromic deafness, manifest non-syndromic deafness, cycloidal atrophy, latent cycloidal atrophy, manifest cycloidal atrophy, cycloidal choroidal atrophy.Vitreoretinal diseases, exudative vitreoretinal diseases, familial exudative vitreoretinal diseases, latent familial exudative vitreoretinal diseases, overt familial exudative vitreoretinal diseases, overt familial exudative vitreoretinal diseases with Kurtz's disease, neovascularization vitreoretinal diseases, latent neovascularization vitreoretinal diseases, overt neovascularization vitreoretinal diseases, macular atrophy, latent macular atrophy, overt macular atrophy, Merkel syndrome, latent Merkel syndrome, overt Merkel syndrome, vitreoretinal choroidal diseases, latent vitreoretinal choroidal diseases, overt vitreoretinal choroidal diseases, yolk sac macular degeneration, latent yolk sac macular degeneration, overt yolk sac macular degeneration Pathological changes, high bone mass trait, latent high bone mass trait, overt high bone mass trait, osteoporosis-pseudoglioma syndrome, latent osteoporosis-pseudoglioma syndrome, overt osteoporosis-pseudoglioma syndrome, microphthalmia, latent microphthalmia, overt microphthalmia, retinal disease syndrome, latent retinal disease syndrome, overt retinal disease syndrome, microphthalmia with retinal disease syndrome, latent microphthalmia with retinal disease syndrome, overt microphthalmia with retinal disease syndrome, true microphthalmia, latent true microphthalmia, overt true microphthalmia, skeletal dysplasia, latent skeletal dysplasia, overt skeletal dysplasia, developmental disorders, osteoarthritis with syndromic disorders, cavitary optic disc abnormalities, latent cavitary optic disc abnormalities, overt... Cryocecal disc abnormalities, white spot fundus, latent white spot fundus, overt white spot fundus, mevalonuria, latent mevalonuria, overt mevalonuria, high IgD syndrome, latent high IgD syndrome, overt high IgD syndrome, spastic paraplegia, latent spastic paraplegia, overt spastic paraplegia, latent spastic paraplegia with neuropathy, latent spastic paraplegia with optic nerve atrophy, latent spastic paraplegia with optic nerve atrophy (dementia) due to neuropathy, latent dementia, overt dementia, familial overt dementia, retinoblastoma, latent retinoblastoma, overt retinoblastoma, germ cell retinoblastoma, somatic cell retinoblastoma, overt germ cell or somatic cell retinoblastoma, optic nerve... Retinoma, benign retinal tumor, pineal tumor, osteosarcoma, rod monochromatic vision, latent rod monochromatic vision, dominant rod monochromatic vision, achromatopsia, latent achromatopsia, dominant achromatopsia, rod achromatopsia, rod latent achromatopsia, rod dominant achromatopsia, latent rod monochromatic vision or achromatopsia, figure-like dystrophy, latent figure-like dystrophy, dominant figure-like dystrophy, S-cone syndrome, enhanced S-cone syndrome (ESC), latent ESC, dominant ESC, Goldman-Favre syndrome, latent Goldman-Favre syndrome, dominant Goldman-Favre syndrome, Portinia dystrophy, latent Portinia dystrophy, dominant Portinia dystrophy, white spot retinal degeneration, latent white spot retinal degeneration.Overt white dot retinal degeneration, mucolipidemia type IIIγ, latent mucolipidemia type IIIγ, overt mucolipidemia type IIIγ, Meinzel-Saldino syndrome, latent Meinzel-Saldino syndrome, overt Meinzel-Saldino syndrome, pseudoxanthoma elasticum, latent pseudoxanthoma elasticum, overt pseudoxanthoma elasticum, Knobloch syndrome, latent Knobloch syndrome, overt Knobloch syndrome, foveal dysplasia, latent foveal dysplasia, overt foveal dysplasia, anterior segment dysplasia, latent anterior segment dysplasia, overt anterior segment dysplasia, foveal dysplasia with anterior segment dysplasia, latent foveal dysplasia with anterior segment dysplasia, overt foveal dysplasia with anterior segment dysplasia, spasticity Ataxia, latent spastic ataxia, overt spastic ataxia, Degroove syndrome, Boucher-Neuhauser syndrome, latent Boucher-Neuhauser syndrome, overt Boucher-Neuhauser syndrome, Boucher-Neuhauser syndrome with choroidal-retinal dystrophy, latent Boucher-Neuhauser syndrome with choroidal-retinal dystrophy, overt Boucher-Neuhauser syndrome with choroidal-retinal dystrophy, hypopre-β-lipoproteinemia-acanthosis-retinitis pigmentosa-globus pallidus (HARP) degeneration, latent HARP degeneration, overt HARP degeneration, Hallewarden-Schpattz syndrome, latent Hallewarden-Schpattz syndrome, overt Hallewarden-Schpattz syndrome, Arager syndrome, latent Arager syndrome Syndrome, Overt Arager's Syndrome, Polyneuropathy-Hearing Loss-Ataxia-Retinitis Pigmentosa-Early-Onset Cataract (PHARC), Latent PHARC, Overt PHARC, Latent Syndromic PHARC, Sotheby's Dystrophy, Latent Sotheby's Dystrophy, Overt Sotheby's Dystrophy, Vitreoretinal Dystrophy, Latent Vitreoretinal Dystrophy, Overt Vitreoretinal Dystrophy, Optic Neuropathy, Latent Optic Neuropathy, Overt Optic Neuropathy, Late-Onset Overt Optic Neuropathy, Orofacial-Finger-Linguistic Syndrome Type 1, Simpson-Goraby-Bemmell Syndrome Type 2, X-Link Retinoschisis, X-Link Oregon Eye Disease, X-Link Optic Atrophy, Retinal Dysplasia Latent retinal dysplasia, manifest retinal dysplasia, X-linked retinal dysplasia, primary X-linked retinal dysplasia, X-linked Norrie's disease, Coulter's disease, X-linked Isle of Ophthalmopathy, autoimmune inner ear disease (AIED), AIED-like disease, achoroidal dysplasia, X-linked achoroidal dysplasia, neuropathy-optic atrophy-deafness-retinitis pigmentosa, X-linked neuropathy-optic atrophy-deafness-retinitis pigmentosa, X-linked blue cone monochromatic vision, X-linked red weakness with rare macular dystrophy blue cone monochromatic vision (BCM), X-linked green weakness with rare macular dystrophy blue cone monochromatic vision (BCM), mitochondrial Karns-Sell syndrome including retinitis pigmentosa,Lechner's syndrome, retinopathy, mitochondrial retinopathy with sensorineural hearing loss, ocular albinism, oculocutaneous albinism, neuronal ceroid lipofuscin deposition, Zelweg spectrum disorder, cobalamin C deficiency, blue cone monochromatic vision with inherited red-green color vision deficiency, blue blindness with yellow-blue color vision deficiency, visual impairment, delayed cone adaptation, uveitis, diabetic retinopathy, diabetic macular edema, persistent corneal epithelial defects, neurotrophic keratitis, herpetic stromal keratitis, chronic dry eye, glaucoma, ocular abrasion, ocular bullae formation, ocular scarring, vision loss, blindness, corneal blindness, and dry eye syndrome, aqueous hypoxic dry eye, Sjögren's syndrome-associated aqueous hypoxic dry eye, non-Sjögren's syndrome-associated dry eye, evaporative dry eye. Type 1 dry eye, meibomian gland dysfunction, blepharitis, blepharitis, ocular erythema with atopic dermatitis, aqueous deficiency with evaporative dry eye, Fuchs dystrophy, Fuchs corneal endothelial dystrophy (FECD), Fuchs endothelial dystrophy (FED), panuveitis, diffuse uveitis, complete uveitis, cataract, partial cataract, complete cataract, stationary cataract, progressive cataract, hard cataract, soft cataract, nuclear cataract, nuclear sclerotic cataract, cortical cataract, posterior subcapsular cataract, congenital cataract, corneal dystrophy, epithelial with subepithelial dystrophy, epithelial basement membrane dystrophy, recurrent epithelial erosive dystrophy (Frances Katie corneal dystrophy, Smorandi dystrophy) The following are types of keratopathy: subepithelial myxoid keratopathy, Missmann keratopathy, Lich epithelial keratopathy, droplet keratopathy, Bowman's keratopathy, Les-Buckles keratopathy, Thiel-Bunk keratopathy, stromal dystrophy - TGFB1 keratopathy, reticular keratopathy, reticular keratopathy type 1 variants (types III, IIIA, I / IIIA, IV), granular keratopathy type 1, granular keratopathy type 2, stromal dystrophy, macular keratopathy, Schneider crystalline keratopathy, congenital stromal keratopathy, punctate keratopathy, and amorphous posterior keratopathy. François Central Cloudy Keratopathy, Desmi's Anterior Keratopathy, Endothelial Dystrophy, Fuchs's Keratopathy, Polymorphic Posterior Keratopathy, Congenital Hereditary Endothelial Dystrophy, X-Linked Endothelial Dystrophy, Superficial Keratopathy, Epithelial Basement Membrane Dystrophy, Missmann's Juvenile Epithelial Keratopathy, Droplet Keratopathy, Lich's Epithelial Keratopathy, Subepithelial Mucinous Keratopathy, Les-Bukler's Keratopathy, Till-Bunker's Keratopathy, Stroma Keratopathy, Reticular Keratopathy, Granular Keratopathy, Macular Keratopathy, Schneider's Crystalline Keratopathy, Congenital Stroma Keratopathy, Spotty Keratopathy, Posterior KeratopathyFuchs dystrophy, posterior polymorphic keratopathy, congenital hereditary endothelial dystrophy, corneal diseases, band keratopathy, corneal band keratopathy, calcified band keratopathy.

60. The herpesvirus or pharmaceutical composition of claim 59, wherein the eye condition or disease is neurotrophic keratitis, Staggart's disease, or Leber congenital amaurosis.

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

62. The herpesvirus or pharmaceutical composition according to claim 59 or claim 60, wherein the eye condition or disease is Staggart disease.

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

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

65. The use according to claim 64, wherein the ocular condition or disease is selected from retinitis pigmentosa, latent retinitis pigmentosa, severe latent retinitis pigmentosa, overt retinitis pigmentosa, overt retinitis pigmentosa with choroidal involvement, latent retinitis pigmentosa with para-arteriolar RPE preservation (PPRPE), latent retinitis pigmentosa with posterior column ataxia (PCARP), latent retinitis pigmentosa with microcytosis, syndromic latent retinitis pigmentosa, latent syndromic disease with retinitis pigmentosa, non-syndromic latent retinitis pigmentosa, non-syndromic overt retinitis pigmentosa, syndromic overt retinitis pigmentosa, juvenile latent retinitis pigmentosa, latent vision Retinitis pigmentosa with intellectual disability, latent retinitis pigmentosa with macular degeneration, severe early-onset latent retinitis pigmentosa, latent retinitis pigmentosa with skeletal abnormalities, latent retinitis pigmentosa with skeletal deformities, overt retinitis pigmentosa with sensorineural hearing loss, latent retinitis pigmentosa with hearing loss, latent retinitis pigmentosa with hearing loss and other impairments, latent retinitis pigmentosa with vitreous changes, early-onset latent retinitis pigmentosa with macular defects, X-linked retinitis pigmentosa, latent X-linked retinitis pigmentosa, overt X-linked retinitis pigmentosa, severe X-linked retinitis pigmentosa, X-linked retinitis pigmentosa with intellectual disability, X-linked retinitis pigmentosa with myopathy. Bald-Biedel syndrome-like retinitis pigmentosa, Bald-Biedel syndrome-like latent retinitis pigmentosa, bigenic retinitis pigmentosa, bigenic retinitis pigmentosa due to abnormality of outer retinal membrane protein 1, bigenic retinitis pigmentosa due to abnormality of PRPH2, latent retinitis pigmentosa with early macular involvement, latent deafness without retinitis pigmentosa, latent congenital deafness without retinitis pigmentosa, latent retinitis pigmentosa with latent ataxia, latent retinitis pigmentosa with dominant ataxia, mitochondrial retinitis pigmentosa, mitochondrial retinitis pigmentosa with developmental and neurological abnormalities, mitochondrial retinitis pigmentosa with progressive sensorineural hearing loss, mitochondrial retinitis pigmentosa Degeneration with deafness and neurological abnormalities; autosomal dominant retinitis pigmentosa; non-syndromic 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-Lukehn syndrome; recessive Senior-Lukehn syndrome; dominant Senior-Lukehn syndrome; renal wasting disease; recessive renal wasting disease; dominant renal wasting disease; juvenile recessive renal wasting disease; ciliopathy-associated recessive renal wasting disease; juvenile renal wasting disease; juvenile recessive renal wasting disease; juvenile dominant renal wasting disease; 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 due to CDH23 abnormality, bigenic Usher syndrome due to PCDH15 abnormality, Acadia recessive Usher syndrome, recessive atypical Usher syndrome (USH3-like), Leber congenital amaurosis Recessive Leber congenital amaurosis, dominant Leber congenital amaurosis, new-onset Leber congenital amaurosis, dominant Leber congenital amaurosis with 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 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, recessive optic atrophy with ataxia and 3-methylpentanoic aciduria, dominant optic atrophy with cataracts, ataxia and areflexia, Kaiser type dominant optic atrophy, dominant optic atrophy with sensorineural hearing loss, recessive cerebellar degeneration Spectral optic atrophy, optic atrophy with deafness-dystonia syndrome, X-linked optic atrophy with deafness-dystonia syndrome, retinal dystrophy, latent retinal dystrophy, overt retinal dystrophy, hereditary retinal dystrophy, early-onset latent retinal dystrophy, latent syndromic retinal dystrophy, latent non-syndromic retinal dystrophy, latent syndromic and non-syndromic retinal dystrophy, latent optic atrophy with retinal dystrophy, latent retinal dystrophy with obesity, latent retinal dystrophy with cerebellar dysplasia, syndromic latent optic atrophy with retinal dystrophy, overt retinal dystrophy with iris defects, ciliary spectrum disorders including retinal dystrophy, including Retinal malnutrition spectrum disorders, including overt retinal malnutrition spectrum disorders, overt optic atrophy with neuropathy and myopathy, overt optic atrophy with intellectual disability and developmental delay, syndromic optic atrophy, non-syndromic optic atrophy, latent non-syndromic optic atrophy, overt non-syndromic optic atrophy, latent syndromic optic atrophy, overt syndromic optic atrophy, Charcot-Marie-Tuss disease, latent Charcot-Marie-Tuss disease, overt Charcot-Marie-Tuss disease, benign punctate retinopathy, latent benign punctate retinopathy, overt benign punctate retinopathy, syndromic retinopathy, latent syndromic retinopathy, overt syndromic retinopathy, Barten disease, latent Barten disease.Dominant Barten disease, Latent Barten disease (neuronal ceroid lipofuscinosis type 3), Juvenile Latent Barten disease (neuronal ceroid lipofuscinosis type 3), Neuronal ceroid lipofuscinosis, Latent Neuronal ceroid lipofuscinosis, Latent Neuronal ceroid lipofuscinosis type 1, Dominant Neuronal ceroid lipofuscinosis, Staggart disease, Latent Staggart disease, Dominant Staggart disease, Juvenile Staggart disease, Late-onset Staggart disease, Staggart disease-like macular dystrophy, Latent Staggart disease-like macular dystrophy, Dominant Staggart disease-like macular dystrophy, Macular dystrophy, Latent macular dystrophy, Early-onset macular dystrophy, Adult-onset macular dystrophy, Early-onset latent macular dystrophy, Adult-onset latent macular dystrophy Benign, early-onset adult-onset latent macular dystrophy, juvenile latent macular dystrophy with sparse hairs, dominant macular dystrophy, late-onset dominant macular dystrophy, dominant macular dystrophy with lens suspensory ligament abnormalities, bull's-eye dominant macular dystrophy, butterfly-shaped dominant macular dystrophy, age-related dominant macular dystrophy, benign concentric ring dominant macular dystrophy, yolk-like latent macular dystrophy, yolk-like dominant macular dystrophy, atypical yolk-like dominant macular dystrophy, dominant adult-onset yolk-like macular dystrophy, Stagger's disease-like dominant macular dystrophy, Stagger's disease-type dominant macular dystrophy, North Carolina-type dominant macular dystrophy, North Carolina-type-like dominant macular dystrophy, North Carolina-type-like with progressive Dominant macular dystrophy, cystoid dominant macular dystrophy, Best type dominant macular dystrophy, occult macular dystrophy, latent occult macular dystrophy, dominant occult macular dystrophy, age-related familial macular dystrophy, X-linked atrophic macular dystrophy, latent X-linked atrophic macular dystrophy, dominant X-linked atrophic macular dystrophy, mitochondrial macular pattern dystrophy with type II diabetes and deafness, xanthomastia, latent xanthomastia, dominant xanthomastia, rod dystrophy, latent rod dystrophy, dominant rod dystrophy, cone dystrophy, latent cone dystrophy, dominant cone dystrophy, latent cone dystrophy Cone dystrophy with abnormal rod electroretinogram, early-onset latent cone dystrophy, late-onset latent cone dystrophy, cone dystrophy type 1, X-linked cone dystrophy type 1, cone dystrophy type 2, progressive cone dystrophy type 2, X-linked progressive cone dystrophy type 2, delayed cone adaptation, delayed latent cone adaptation, delayed manifest cone adaptation, cone-rod dystrophy, latent cone-rod dystrophy, manifest cone-rod dystrophy, isolated cone-rod dystrophy, progressive cone-rod dystrophy, X-linked cone-rod dystrophy, X-linked progressive cone-rod dystrophy, progressive manifest cone-rod dystrophy, cone-rod dystrophy with enamel hypoplasia syndrome.Latent cone-rod dystrophy with enamel hypoplasia syndrome, dominant cone-rod dystrophy with enamel hypoplasia syndrome, latent cone-rod dystrophy with inner retinal lesions, latent cone-rod dystrophy with skeletal diseases, congenital syndromic non-progressive latent cone-rod dystrophy, latent cone-rod dystrophy with hearing loss, latent cone-rod dystrophy with psychomotor delay, latent cone with cone-rod dystrophy, cone-rod synaptic disorders, congenital cone-rod synaptic disorders, latent congenital cone-rod synaptic disorders, dominant congenital cone-rod synaptic disorders, rod-cone dystrophy, latent cone-rod dystrophy, dominant rod-cone dystrophy, early-onset Latent rod-cone dystrophy, non-syndromic latent rod-cone dystrophy, latent Newfoundland type rod-cone dystrophy, latent progressive cone dystrophy, Stickler syndrome, dominant Stickler syndrome, latent Stickler syndrome, dominant Stickler syndrome type I, dominant Stickler syndrome type II, Marshall syndrome, dominant Marshall syndrome, latent Marshall syndrome, achromatopsia, latent achromatopsia, dominant achromatopsia, latent complete achromatopsia, latent incomplete achromatopsia, 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, latent drusen, dominant Drupial condyloma, early-onset latent drupture, early-onset dominant drupture, macular drupture, dominant radial macular drupture, pigmented paravenous choroidal retinal atrophy, latent pigmented paravenous choroidal retinal atrophy, dominant pigmented paravenous choroidal retinal atrophy, progressive bifocal choroidal retinal atrophy, Balde-Biedel syndrome, latent Balde-Biedel syndrome, dominant Balde-Biedel syndrome, latent Balde-Biedel syndrome with developmental abnormalities, retinal degeneration, latent retinal degeneration, dominant retinal degeneration, non-syndromic latent retinal degeneration, multifactorial celluloid retinal degeneration, latent multifactorial celluloid retinal degeneration, dominant multifactorial celluloid retinal degeneration (Leventinese disease), latent renal wasting disease with retinal Membrane degeneration, Alstrom syndrome, latent Alstrom syndrome, dominant Alstrom syndrome, Jupiter syndrome, latent Jupiter syndrome, dominant Jupiter syndrome, Jobel syndrome, latent Jobel syndrome, dominant Jobel syndrome, X-linked Jobel syndrome, vitreoretinal degeneration, latent vitreoretinal degeneration, dominant vitreoretinal degeneration, snowflake vitreoretinal degeneration, snowflake dominant vitreoretinal degeneration, microstomia, latent microstomia, dominant microstomia, night blindness, stationary night blindness, congenital night blindness, congenital stationary night blindness, severe congenital stationary night blindness, latent congenital stationary night blindness, latent complete congenital stationary night blindness, dominant congenital stationary night blindness.Nogaret type dominant congenital static night blindness, microstomia type latent congenital static night blindness, Riggs type latent congenital static night blindness, Schubert-Bornshain type latent congenital static night blindness, white spot fundus type latent congenital static night blindness, complete latent congenital static night blindness, X-linked congenital static night blindness, incomplete X-linked congenital static night blindness, retinal vascular disease, leukodystrophy, retinal vascular disease with leukodystrophy, latent retinal vascular disease with leukodystrophy, dominant retinal vascular disease with leukodystrophy, Ecardi-Gutier syndrome, Ecardi-Gutier syndrome type 1, latent Ecardi-Gutier syndrome type 1, dominant Ecardi-Gutier syndrome. Erdi-Gutier syndrome type 1, frostbite-like lupus, latent frostbite-like lupus, overt frostbite-like lupus, Martinic retinal dystrophy with retinitis pigmentosa, latent Martinic retinal dystrophy with retinitis pigmentosa, overt Martinic retinal dystrophy with retinitis pigmentosa, spinocerebellar ataxia, latent spinocerebellar ataxia, overt spinocerebellar ataxia, spinocerebellar ataxia with macular dystrophy, spinocerebellar ataxia with retinal degeneration, spinocerebellar ataxia with macular dystrophy or retinal degeneration, latent spinocerebellar ataxia with macular dystrophy or retinal degeneration, overt spinocerebellar ataxia with macular dystrophy or retinal degeneration, Wolfram syndrome Symptoms, Latent Wolveram syndrome, Overt Wolveram syndrome, Low-frequency sensorineural hearing loss, Latent low-frequency sensorineural hearing loss, Overt low-frequency sensorineural hearing loss, Eye and ear syndrome, Latent eye and ear syndrome, Overt eye and ear syndrome, Latent kidney, skeletal and retinal abnormalities, Latent abelasmoproteinemia, Microcephaly, Latent microcephaly, Overt microcephaly, Latent microcephaly with growth retinal disease, Biedi crystalline keratoretinal dystrophy, Latent pedunculated crystalline keratoretinal dystrophy, Overt pedunculated crystalline keratoretinal dystrophy, Wagner's disease, Erosive vitreoretinopathy, Wagner's disease with erosive vitreoretinopathy, Latent Wagner's disease with erosive vitreoretinopathy Overt Wagner's disease with erosive vitreoretinopathy, febrile seizures, latent febrile seizures, overt febrile seizures, overt / latent febrile seizures, choroidal dystrophy, latent choroidal dystrophy, overt choroidal dystrophy, central halo choroidal dystrophy, overt central halo choroidal dystrophy, latent central halo choroidal dystrophy, epiphyseal dysplasia, latent epiphyseal dysplasia, overt epiphyseal dysplasia, multiple epiphyseal dysplasia, latent multiple epiphyseal dysplasia, overt multiple epiphyseal dysplasia, ichthyosis, latent ichthyosis, overt ichthyosis, latent ichthyosis with quadriplegia, choroidal-retinal atrophy, bifocal choroidal-retinal atrophy, progressive bifocal choroidal-retinal atrophy.Latent progressive bifocal chorioretinal atrophy, dominant progressive bifocal chorioretinal atrophy, Rifsum disease, latent Rifsum disease, dominant Rifsum disease, adult latent Rifsum disease, infantile latent Rifsum disease, retinal-cone dystrophy, latent retinal-cone dystrophy, dominant retinal-cone dystrophy, retinal-cone dystrophy type 1, latent retinal-cone dystrophy type 1, dominant retinal-cone dystrophy type 1, blue-yellow color blindness, latent blue-yellow color blindness, dominant blue-yellow color blindness, mucopolysaccharidosis, latent mucopolysaccharidosis, dominant mucopolysaccharidosis, Pinglap achromatopsia, latent Pinglap achromatopsia, dominant Pinglap achromatopsia, Klippel-Fair syndrome, latent Klippel syndrome Per Fell syndrome, dominant Krippel-Fell syndrome, microphthalmia, latent microphthalmia, dominant microphthalmia, limb-girdle muscular dystrophy, latent limb-girdle muscular dystrophy, dominant limb-girdle muscular dystrophy, short-rib thoracic dysplasia, latent short-rib thoracic dysplasia, dominant short-rib thoracic dysplasia, latent short-rib thoracic dysplasia with polydactyly, latent short-rib thoracic dysplasia with retinal dystrophy, intellectual disability-trunk obesity-retinal dystrophy-micropenis (MORM) syndrome, latent MORM syndrome, dominant MORM syndrome, latent retinal delay with spasticity and retinal degeneration, Cockayne syndrome, latent Cockayne syndrome, dominant Cockayne syndrome, congenital retinal detachment, latent nonsyndromic congenital retinal retina Retinal detachment, dominant non-syndromic congenital retinal detachment, hemolytic anemia, nonspherocytic hemolytic anemia, latent nonspherocytic hemolytic anemia, dominant nonspherocytic hemolytic anemia, hereditary neuropathy, hereditary neuropathy (Russian type), latent hereditary neuropathy (Russian type), dominant hereditary neuropathy (Russian type), choroidal sclerosis, latent choroidal sclerosis, dominant choroidal sclerosis, retinopathy, latent retinopathy, dominant retinopathy, dominant and latent combined retinopathy, diffuse dominant retinopathy, variant dominant retinopathy, diffuse retinopathy with variant dominant retinopathy, microcephaly, latent microcephaly, dominant microcephaly, dominant microcephaly with lymphedema, choroidal retina Overt microcephaly due to membranous lesions, overt microcephaly due to lymphedema with choroidal retinal lesions, choroidal retinal lesions, latent choroidal retinal lesions, overt choroidal retinal lesions, choroidal retinal lesions with microcephaly, latent choroidal retinal lesions with microcephaly, overt choroidal retinal lesions with microcephaly, renal defect syndrome, latent renal defect syndrome, overt renal defect syndrome, non-syndromic deafness, latent non-syndromic deafness, overt non-syndromic deafness, cycloplegic atrophy, latent cycloplegic atrophy, overt cycloplegic atrophy, cycloplegic choroidal atrophy, vitreoretinal lesions, exudative vitreoretinal lesions, familial exudative vitreoretinal lesions, latent familial exudative vitreoretinal lesions,Overt familial exudative vitreoretinopathy, overt familial exudative vitreoretinopathy with Kurtz's disease, neovascularization vitreoretinopathy, latent neovascularization vitreoretinopathy, overt neovascularization vitreoretinopathy, macular atrophy, latent macular atrophy, overt macular atrophy, Merkel syndrome, latent Merkel syndrome, overt Merkel syndrome, vitreoretinal choroidal disease, latent vitreoretinal choroidal disease, overt vitreoretinal choroidal disease, yolk sac macular degeneration, latent yolk sac macular degeneration, overt yolk sac macular degeneration, high bone mass trait, latent high bone mass trait, overt high bone mass trait, osteoporosis-pseudoglioma syndrome, latent osteoporosis-pseudoglioma syndrome Glioma syndrome, overt osteoporosis-pseudoglioma syndrome, microphthalmia, latent microphthalmia, overt microphthalmia, retinal disease syndrome, latent retinal disease syndrome, overt retinal disease syndrome, microphthalmia with retinal disease syndrome, latent microphthalmia with retinal disease syndrome, overt microphthalmia with retinal disease syndrome, true microphthalmia, latent true microphthalmia, overt true microphthalmia, skeletal dysplasia, latent skeletal dysplasia, overt skeletal dysplasia, developmental disorders, osteoarthritis with syndromic disorders, cavitary optic disc abnormalities, latent cavitary optic disc abnormalities, overt cavitary optic disc abnormalities, white spot fundus, latent white spot fundus, overt white spot fundus, mevalonateuria, latent mevalonateuria, overt... Mevalonuria, HyperIgD syndrome, Latent hyperIgD syndrome, Overt hyperIgD syndrome, Spastic paraplegia, Latent spastic paraplegia, Overt spastic paraplegia, Latent spastic paraplegia with neuropathy, Latent spastic paraplegia with optic atrophy, Latent spastic paraplegia with optic atrophy (dementia) due to neuropathy, Latent dementia, Overt dementia, Familial overt dementia, Retinoblastoma, Latent retinoblastoma, Overt retinoblastoma, Germ cell retinoblastoma, Somatic cell retinoblastoma, Overt germ cell or somatic cell retinoblastoma, Retinoblastoma, Benign retinoblastoma, Pineal tumor, Osteosarcoma, Rod monochromatic vision, Latent rod monochromatic vision, Overt rod monochromatic vision, Achromatopsia Latent achromatopsia, dominant achromatopsia, rod achromatopsia, rod latent achromatopsia, rod dominant achromatopsia, latent rod monochromatic vision or achromatopsia, figure-like malnutrition, latent figure-like malnutrition, dominant figure-like malnutrition, S-cone syndrome, enhanced S-cone syndrome (ESC), latent ESC, dominant ESC, Goldman-Favre syndrome, latent Goldman-Favre syndrome, dominant Goldman-Favre syndrome, Portinia malnutrition, latent Portinia malnutrition, dominant Portinia malnutrition, white spot retinal degeneration, latent white spot retinal degeneration, dominant white spot retinal degeneration, mucosal storage disease type IIIγ, latent mucosal storage disease type IIIγ, dominant mucosal storage disease type IIIγ.Meinzel-Saldino syndrome, recessive Meinzel-Saldino syndrome, dominant Meinzel-Saldino syndrome, pseudoxanthoma elastica, recessive pseudoxanthoma elastica, dominant pseudoxanthoma elastica, Knobloch syndrome, recessive Knobloch syndrome, dominant Knobloch syndrome, foveal dysplasia, recessive foveal dysplasia, dominant foveal dysplasia, anterior segment dysplasia, recessive anterior segment dysplasia, dominant anterior segment dysplasia, foveal dysplasia with anterior segment dysplasia, recessive foveal dysplasia with anterior segment dysplasia, dominant foveal dysplasia with anterior segment dysplasia, spastic ataxia, recessive spastic ataxia, dominant spastic ataxia, Degroove syndrome, Boucher-Neuhauser syndrome, recessive Boucher-Neuhauser syndrome - Neuhauser syndrome, dominant Boucher-Neuhauser syndrome, Boucher-Neuhauser syndrome with choroidal retinal dystrophy, latent Boucher-Neuhauser syndrome with choroidal retinal dystrophy, dominant Boucher-Neuhauser syndrome with choroidal retinal dystrophy, hypopre-β-lipoproteinemia, acanthosis, retinitis pigmentosa, globus pallidus (HARP) degeneration, latent HARP degeneration, dominant HARP degeneration, Hallewarden-Schpattz syndrome, latent Hallewarden-Schpattz syndrome, dominant Hallewarden-Schpattz syndrome, Arager syndrome, latent Arager syndrome, dominant Arager syndrome, polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, early-onset cataract (PH) ARC), latent PHARC, overt PHARC, latent syndromic PHARC, Sotheby's dystrophy, latent Sotheby's dystrophy, overt Sotheby's dystrophy, vitreoretinal dystrophy, latent vitreoretinal dystrophy, overt vitreoretinal dystrophy, optic neuropathy, latent optic neuropathy, overt optic neuropathy, late-onset overt optic neuropathy, orofacial-finger syndrome type 1, Simpson-Goraby-Bemmell syndrome type 2, X-linked retinoschisis, X-linked Oregon ophthalmopathy, X-linked optic atrophy, retinal dysplasia, latent retinal dysplasia, overt retinal dysplasia, X-linked retinal dysplasia, primary X-linked retinal dysplasia X-linked Norrie disease, Coates' disease, X-linked Isle of Ophthalmopathy, Autoimmune Inner Otopathy (AIED), AIED-like diseases, Achoroidal disease, X-linked Achoroidal disease, Neuropathy-Optical Atrophy-Deafness-Retinitis Pigmentosa, X-linked Neuropathy-Optical Atrophy-Deafness-Retinitis Pigmentosa, X-linked Blue Cone Monochromatic Vision, X-linked Red Weakness with Rare Macular Dystrophy Blue Cone Monochromatic Vision (BCM), X-linked Green Weakness with Rare Macular Dystrophy Blue Cone Monochromatic Vision (BCM), Mitochondrial Karnes-Sell Syndrome including Retinitis Pigmentosa, Leigh syndrome, Retinopathy, Mitochondrial Retinitis Pigmentosa with Sensorineural Hearing Loss, Ocular Albinism, Oculocutaneous AlbinismNeuronal ceroid lipofuscin deposition, Zelweg spectrum disorder, cobalamin C deficiency, blue cone monochromatic vision inherited red-green color vision deficiency, blue blindness with yellow-blue color vision deficiency, visual impairment, delayed cone adaptation, uveitis, diabetic retinopathy, diabetic macular edema, persistent corneal epithelial defects, neurotrophic keratitis, herpetic stromal keratitis, chronic dry eye, glaucoma, ocular abrasion, ocular bullae formation, ocular scarring, vision loss, blindness, corneal blindness, dry eye syndrome, aqueous hypoxic dry eye syndrome, Sjögren's syndrome-related aqueous hypoxic dry eye syndrome, non-Sjögren's syndrome-related dry eye syndrome, evaporative dry eye syndrome, meibomian gland dysfunction, blepharitis, blepharitis, ocular erythema acne with atopic dermatitis, aqueous hypoxic dry eye syndrome with evaporative dry eye syndrome, rich in... Fuchs dystrophy, Fuchs endothelial dystrophy (FECD), Fuchs endothelial dystrophy (FED), panuveitis, diffuse uveitis, complete uveitis, cataract, partial cataract, complete cataract, stationary cataract, progressive cataract, hard cataract, soft cataract, nuclear cataract, nuclear sclerotic cataract, cortical cataract, posterior subcapsular cataract, congenital cataract, corneal dystrophy, epithelial with subepithelial dystrophy, epithelial basement membrane dystrophy, recurrent epithelial erosive dystrophy (Francescatti keratopathy, Smorandi dystrophy and / or Helsinglandia dystrophy), subepithelial myxoid keratopathy, Missmann keratopathy, Lich epithelial keratopathy Malnutrition, droplet keratopathy, Bowman's keratopathy, Les-Buckles keratopathy, Thiel-Bunk keratopathy, stromal dystrophy - TGFB1 keratopathy, reticulate keratopathy, reticulate keratopathy type 1 variants (type III, IIIA, I / IIIA, IV), granular keratopathy type 1, granular keratopathy type 2, stromal dystrophy, macular keratopathy, Schneider crystalline keratopathy, congenital stromal keratopathy, punctate keratopathy, amorphous posterior keratopathy, François central cloud keratopathy, Desmi anterior keratopathy, endothelial dystrophy, Fuchs keratopathy, polymorphism Posterior corneal dystrophy, congenital hereditary endothelial dystrophy, X-linked endothelial dystrophy, superficial corneal dystrophy, epithelial basement membrane dystrophy, Missmann juvenile epithelial dystrophy, droplet keratopathy, Lich epithelial dystrophy, subepithelial mucinous keratopathy, Les-Buckles keratopathy, Thiel-Bunk dystrophy, stromal dystrophy, reticular keratopathy, granular keratopathy, macular keratopathy, Schneider crystalline keratopathy, congenital stromal keratopathy, punctate keratopathy, posterior corneal dystrophy, Fuchs dystrophy, polymorphic posterior corneal dystrophy, congenital hereditary endothelial dystrophy, corneal diseases, band keratopathy,Band keratopathy and calcified band keratopathy.

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

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

68. The use according to any one of claims 64-66, wherein the eye condition or disease is Staggart's disease.

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

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

71. The method of 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, Miller cells, or cells without long processes.

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

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

74. The method according to claim 72 or claim 73, wherein the ocular condition or disease is selected from retinitis pigmentosa, latent retinitis pigmentosa, severe latent retinitis pigmentosa, overt retinitis pigmentosa, overt retinitis pigmentosa with choroidal involvement, latent retinitis pigmentosa with para-arteriolar retinopathy (PPRPE), latent retinitis pigmentosa with posterior column ataxia (PCARP), latent retinitis pigmentosa with microcytic polycythemia, syndromic latent retinitis pigmentosa, latent syndromic disease with retinitis pigmentosa, non-syndromic latent retinitis pigmentosa, non-syndromic overt retinitis pigmentosa, syndromic overt retinitis pigmentosa, and juvenile latent retinitis pigmentosa. Latent retinitis pigmentosa with intellectual disability, latent retinitis pigmentosa with macular degeneration, severe early-onset latent retinitis pigmentosa, latent retinitis pigmentosa with skeletal abnormalities, latent retinitis pigmentosa with skeletal deformities, overt retinitis pigmentosa with sensorineural hearing loss, latent retinitis pigmentosa with hearing loss, latent retinitis pigmentosa with hearing loss and other impairments, latent retinitis pigmentosa with vitreous changes, early-onset latent retinitis pigmentosa with macular defects, X-linked retinitis pigmentosa, latent X-linked retinitis pigmentosa, overt X-linked retinitis pigmentosa, severe X-linked retinitis pigmentosa, X-linked retinitis pigmentosa with intellectual disability, X-linked retinitis pigmentosa Sexually associated myopathy, Bald-Biedel syndrome-like retinitis pigmentosa, Bald-Biedel syndrome-like latent retinitis pigmentosa, bigenic retinitis pigmentosa, bigenic retinitis pigmentosa due to abnormality of outer retinal membrane protein 1, bigenic retinitis pigmentosa due to abnormality of PRPH2, latent retinitis pigmentosa with early macular involvement, latent deafness without retinitis pigmentosa, latent congenital deafness without retinitis pigmentosa, latent retinitis pigmentosa with latent ataxia, latent retinitis pigmentosa with dominant ataxia, mitochondrial retinitis pigmentosa, mitochondrial retinitis pigmentosa with developmental and neurological abnormalities, mitochondrial retinitis pigmentosa with progressive sensorineural hearing loss, mitochondrial retinal Retinitis pigmentosa with deafness and neurological abnormalities; autosomal dominant retinitis pigmentosa; non-syndromic 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; Sinier-Lukehn syndrome; recessive Sinier-Lukehn syndrome; dominant Sinier-Lukehn syndrome; renal wasting disease; recessive renal wasting disease; dominant renal wasting disease; juvenile recessive renal wasting disease; ciliopathy-associated recessive renal wasting disease; juvenile renal wasting disease; juvenile recessive renal wasting disease; juvenile dominant renal wasting disease; 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 due to CDH23 abnormality, bigenic Usher syndrome due to PCDH15 abnormality, Acadia recessive Usher syndrome, recessive atypical Usher syndrome (USH3-like), Leber congenital amaurosis Recessive Leber congenital amaurosis, dominant Leber congenital amaurosis, new-onset Leber congenital amaurosis, dominant Leber congenital amaurosis with 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 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, recessive optic atrophy with ataxia and 3-methylpentanoic aciduria, dominant optic atrophy with cataracts, ataxia and areflexia, Kaiser type dominant optic atrophy, dominant optic atrophy with sensorineural hearing loss, recessive cerebellar degeneration Spectral optic atrophy, optic atrophy with deafness-dystonia syndrome, X-linked optic atrophy with deafness-dystonia syndrome, retinal dystrophy, latent retinal dystrophy, overt retinal dystrophy, hereditary retinal dystrophy, early-onset latent retinal dystrophy, latent syndromic retinal dystrophy, latent non-syndromic retinal dystrophy, latent syndromic and non-syndromic retinal dystrophy, latent optic atrophy with retinal dystrophy, latent retinal dystrophy with obesity, latent retinal dystrophy with cerebellar dysplasia, syndromic latent optic atrophy with retinal dystrophy, overt retinal dystrophy with iris defects, ciliary spectrum disorders including retinal dystrophy, including Retinal malnutrition spectrum disorders, including overt retinal malnutrition spectrum disorders, overt optic atrophy with neuropathy and myopathy, overt optic atrophy with intellectual disability and developmental delay, syndromic optic atrophy, non-syndromic optic atrophy, latent non-syndromic optic atrophy, overt non-syndromic optic atrophy, latent syndromic optic atrophy, overt syndromic optic atrophy, Charcot-Marie-Tuss disease, latent Charcot-Marie-Tuss disease, overt Charcot-Marie-Tuss disease, benign punctate retinopathy, latent benign punctate retinopathy, overt benign punctate retinopathy, syndromic retinopathy, latent syndromic retinopathy, overt syndromic retinopathy, Barten disease, latent Barten disease.Dominant Barten disease, Latent Barten disease (neuronal ceroid lipofuscinosis type 3), Juvenile Latent Barten disease (neuronal ceroid lipofuscinosis type 3), Neuronal ceroid lipofuscinosis, Latent Neuronal ceroid lipofuscinosis, Latent Neuronal ceroid lipofuscinosis type 1, Dominant Neuronal ceroid lipofuscinosis, Staggart disease, Latent Staggart disease, Dominant Staggart disease, Juvenile Staggart disease, Late-onset Staggart disease, Staggart disease-like macular dystrophy, Latent Staggart disease-like macular dystrophy, Dominant Staggart disease-like macular dystrophy, Macular dystrophy, Latent macular dystrophy, Early-onset macular dystrophy, Adult-onset macular dystrophy, Early-onset latent macular dystrophy, Adult-onset latent macular dystrophy Benign, early-onset adult-onset latent macular dystrophy, juvenile latent macular dystrophy with sparse hairs, dominant macular dystrophy, late-onset dominant macular dystrophy, dominant macular dystrophy with lens suspensory ligament abnormalities, bull's-eye dominant macular dystrophy, butterfly-shaped dominant macular dystrophy, age-related dominant macular dystrophy, benign concentric ring dominant macular dystrophy, yolk-like latent macular dystrophy, yolk-like dominant macular dystrophy, atypical yolk-like dominant macular dystrophy, dominant adult-onset yolk-like macular dystrophy, Stagger's disease-like dominant macular dystrophy, Stagger's disease-type dominant macular dystrophy, North Carolina-type dominant macular dystrophy, North Carolina-type-like dominant macular dystrophy, North Carolina-type-like with progressive Dominant macular dystrophy, cystoid dominant macular dystrophy, Best type dominant macular dystrophy, occult macular dystrophy, latent occult macular dystrophy, dominant occult macular dystrophy, age-related familial macular dystrophy, X-linked atrophic macular dystrophy, latent X-linked atrophic macular dystrophy, dominant X-linked atrophic macular dystrophy, mitochondrial macular pattern dystrophy with type II diabetes and deafness, xanthomastia, latent xanthomastia, dominant xanthomastia, rod dystrophy, latent rod dystrophy, dominant rod dystrophy, cone dystrophy, latent cone dystrophy, dominant cone dystrophy, latent cone dystrophy Cone dystrophy with abnormal rod electroretinogram, early-onset latent cone dystrophy, late-onset latent cone dystrophy, cone dystrophy type 1, X-linked cone dystrophy type 1, cone dystrophy type 2, progressive cone dystrophy type 2, X-linked progressive cone dystrophy type 2, delayed cone adaptation, delayed latent cone adaptation, delayed manifest cone adaptation, cone-rod dystrophy, latent cone-rod dystrophy, manifest cone-rod dystrophy, isolated cone-rod dystrophy, progressive cone-rod dystrophy, X-linked cone-rod dystrophy, X-linked progressive cone-rod dystrophy, progressive manifest cone-rod dystrophy, cone-rod dystrophy with enamel hypoplasia syndrome.Latent cone-rod dystrophy with enamel hypoplasia syndrome, dominant cone-rod dystrophy with enamel hypoplasia syndrome, latent cone-rod dystrophy with inner retinal lesions, latent cone-rod dystrophy with skeletal diseases, congenital syndromic non-progressive latent cone-rod dystrophy, latent cone-rod dystrophy with hearing loss, latent cone-rod dystrophy with psychomotor delay, latent cone with cone-rod dystrophy, cone-rod synaptic disorders, congenital cone-rod synaptic disorders, latent congenital cone-rod synaptic disorders, dominant congenital cone-rod synaptic disorders, rod-cone dystrophy, latent cone-rod dystrophy, dominant rod-cone dystrophy, early-onset Latent rod-cone dystrophy, non-syndromic latent rod-cone dystrophy, latent Newfoundland type rod-cone dystrophy, latent progressive cone dystrophy, Stickler syndrome, dominant Stickler syndrome, latent Stickler syndrome, dominant Stickler syndrome type I, dominant Stickler syndrome type II, Marshall syndrome, dominant Marshall syndrome, latent Marshall syndrome, achromatopsia, latent achromatopsia, dominant achromatopsia, latent complete achromatopsia, latent incomplete achromatopsia, 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, latent drusen, dominant Drupial condyloma, early-onset latent drupture, early-onset dominant drupture, macular drupture, dominant radial macular drupture, pigmented paravenous choroidal retinal atrophy, latent pigmented paravenous choroidal retinal atrophy, dominant pigmented paravenous choroidal retinal atrophy, progressive bifocal choroidal retinal atrophy, Balde-Biedel syndrome, latent Balde-Biedel syndrome, dominant Balde-Biedel syndrome, latent Balde-Biedel syndrome with developmental abnormalities, retinal degeneration, latent retinal degeneration, dominant retinal degeneration, non-syndromic latent retinal degeneration, multifactorial celluloid retinal degeneration, latent multifactorial celluloid retinal degeneration, dominant multifactorial celluloid retinal degeneration (Leventinese disease), latent renal wasting disease with retinal Membrane degeneration, Alstrom syndrome, latent Alstrom syndrome, dominant Alstrom syndrome, Jupiter syndrome, latent Jupiter syndrome, dominant Jupiter syndrome, Jobel syndrome, latent Jobel syndrome, dominant Jobel syndrome, X-linked Jobel syndrome, vitreoretinal degeneration, latent vitreoretinal degeneration, dominant vitreoretinal degeneration, snowflake vitreoretinal degeneration, snowflake dominant vitreoretinal degeneration, microstomia, latent microstomia, dominant microstomia, night blindness, stationary night blindness, congenital night blindness, congenital stationary night blindness, severe congenital stationary night blindness, latent congenital stationary night blindness, latent complete congenital stationary night blindness, dominant congenital stationary night blindness.Nogaret type dominant congenital static night blindness, microstomia type latent congenital static night blindness, Riggs type latent congenital static night blindness, Schubert-Bornshain type latent congenital static night blindness, white spot fundus type latent congenital static night blindness, complete latent congenital static night blindness, X-linked congenital static night blindness, incomplete X-linked congenital static night blindness, retinal vascular disease, leukodystrophy, retinal vascular disease with leukodystrophy, latent retinal vascular disease with leukodystrophy, dominant retinal vascular disease with leukodystrophy, Ecardi-Gutier syndrome, Ecardi-Gutier syndrome type 1, latent Ecardi-Gutier syndrome type 1, dominant Ecardi-Gutier syndrome. Erdi-Gutier syndrome type 1, frostbite-like lupus, latent frostbite-like lupus, overt frostbite-like lupus, Martinic retinal dystrophy with retinitis pigmentosa, latent Martinic retinal dystrophy with retinitis pigmentosa, overt Martinic retinal dystrophy with retinitis pigmentosa, spinocerebellar ataxia, latent spinocerebellar ataxia, overt spinocerebellar ataxia, spinocerebellar ataxia with macular dystrophy, spinocerebellar ataxia with retinal degeneration, spinocerebellar ataxia with macular dystrophy or retinal degeneration, latent spinocerebellar ataxia with macular dystrophy or retinal degeneration, overt spinocerebellar ataxia with macular dystrophy or retinal degeneration, Wolfram syndrome Symptoms, Latent Wolveram syndrome, Overt Wolveram syndrome, Low-frequency sensorineural hearing loss, Latent low-frequency sensorineural hearing loss, Overt low-frequency sensorineural hearing loss, Eye and ear syndrome, Latent eye and ear syndrome, Overt eye and ear syndrome, Latent kidney, skeletal and retinal abnormalities, Latent abelasmoproteinemia, Microcephaly, Latent microcephaly, Overt microcephaly, Latent microcephaly with growth retinal disease, Biedi crystalline keratoretinal dystrophy, Latent pedunculated crystalline keratoretinal dystrophy, Overt pedunculated crystalline keratoretinal dystrophy, Wagner's disease, Erosive vitreoretinopathy, Wagner's disease with erosive vitreoretinopathy, Latent Wagner's disease with erosive vitreoretinopathy Overt Wagner's disease with erosive vitreoretinopathy, febrile seizures, latent febrile seizures, overt febrile seizures, overt / latent febrile seizures, choroidal dystrophy, latent choroidal dystrophy, overt choroidal dystrophy, central halo choroidal dystrophy, overt central halo choroidal dystrophy, latent central halo choroidal dystrophy, epiphyseal dysplasia, latent epiphyseal dysplasia, overt epiphyseal dysplasia, multiple epiphyseal dysplasia, latent multiple epiphyseal dysplasia, overt multiple epiphyseal dysplasia, ichthyosis, latent ichthyosis, overt ichthyosis, latent ichthyosis with quadriplegia, choroidal-retinal atrophy, bifocal choroidal-retinal atrophy, progressive bifocal choroidal-retinal atrophy.Latent progressive bifocal chorioretinal atrophy, dominant progressive bifocal chorioretinal atrophy, Rifsum disease, latent Rifsum disease, dominant Rifsum disease, adult latent Rifsum disease, infantile latent Rifsum disease, retinal-cone dystrophy, latent retinal-cone dystrophy, dominant retinal-cone dystrophy, retinal-cone dystrophy type 1, latent retinal-cone dystrophy type 1, dominant retinal-cone dystrophy type 1, blue-yellow color blindness, latent blue-yellow color blindness, dominant blue-yellow color blindness, mucopolysaccharidosis, latent mucopolysaccharidosis, dominant mucopolysaccharidosis, Pinglap achromatopsia, latent Pinglap achromatopsia, dominant Pinglap achromatopsia, Klippel-Fair syndrome, latent Klippel syndrome Per Fell syndrome, dominant Krippel-Fell syndrome, microphthalmia, latent microphthalmia, dominant microphthalmia, limb-girdle muscular dystrophy, latent limb-girdle muscular dystrophy, dominant limb-girdle muscular dystrophy, short-rib thoracic dysplasia, latent short-rib thoracic dysplasia, dominant short-rib thoracic dysplasia, latent short-rib thoracic dysplasia with polydactyly, latent short-rib thoracic dysplasia with retinal dystrophy, intellectual disability-trunk obesity-retinal dystrophy-micropenis (MORM) syndrome, latent MORM syndrome, dominant MORM syndrome, latent retinal delay with spasticity and retinal degeneration, Cockayne syndrome, latent Cockayne syndrome, dominant Cockayne syndrome, congenital retinal detachment, latent nonsyndromic congenital retinal retina Retinal detachment, dominant non-syndromic congenital retinal detachment, hemolytic anemia, nonspherocytic hemolytic anemia, latent nonspherocytic hemolytic anemia, dominant nonspherocytic hemolytic anemia, hereditary neuropathy, hereditary neuropathy (Russian type), latent hereditary neuropathy (Russian type), dominant hereditary neuropathy (Russian type), choroidal sclerosis, latent choroidal sclerosis, dominant choroidal sclerosis, retinopathy, latent retinopathy, dominant retinopathy, dominant and latent combined retinopathy, diffuse dominant retinopathy, variant dominant retinopathy, diffuse retinopathy with variant dominant retinopathy, microcephaly, latent microcephaly, dominant microcephaly, dominant microcephaly with lymphedema, choroidal retina Overt microcephaly due to membranous lesions, overt microcephaly due to lymphedema with choroidal retinal lesions, choroidal retinal lesions, latent choroidal retinal lesions, overt choroidal retinal lesions, choroidal retinal lesions with microcephaly, latent choroidal retinal lesions with microcephaly, overt choroidal retinal lesions with microcephaly, renal defect syndrome, latent renal defect syndrome, overt renal defect syndrome, non-syndromic deafness, latent non-syndromic deafness, overt non-syndromic deafness, cycloplegic atrophy, latent cycloplegic atrophy, overt cycloplegic atrophy, cycloplegic choroidal atrophy, vitreoretinal lesions, exudative vitreoretinal lesions, familial exudative vitreoretinal lesions, latent familial exudative vitreoretinal lesions,Overt familial exudative vitreoretinopathy, overt familial exudative vitreoretinopathy with Kurtz's disease, neovascularization vitreoretinopathy, latent neovascularization vitreoretinopathy, overt neovascularization vitreoretinopathy, macular atrophy, latent macular atrophy, overt macular atrophy, Merkel syndrome, latent Merkel syndrome, overt Merkel syndrome, vitreoretinal choroidal disease, latent vitreoretinal choroidal disease, overt vitreoretinal choroidal disease, yolk sac macular degeneration, latent yolk sac macular degeneration, overt yolk sac macular degeneration, high bone mass trait, latent high bone mass trait, overt high bone mass trait, osteoporosis-pseudoglioma syndrome, latent osteoporosis-pseudoglioma syndrome Glioma syndrome, overt osteoporosis-pseudoglioma syndrome, microphthalmia, latent microphthalmia, overt microphthalmia, retinal disease syndrome, latent retinal disease syndrome, overt retinal disease syndrome, microphthalmia with retinal disease syndrome, latent microphthalmia with retinal disease syndrome, overt microphthalmia with retinal disease syndrome, true microphthalmia, latent true microphthalmia, overt true microphthalmia, skeletal dysplasia, latent skeletal dysplasia, overt skeletal dysplasia, developmental disorders, osteoarthritis with syndromic disorders, cavitary optic disc abnormalities, latent cavitary optic disc abnormalities, overt cavitary optic disc abnormalities, white spot fundus, latent white spot fundus, overt white spot fundus, mevalonateuria, latent mevalonateuria, overt... Mevalonuria, HyperIgD syndrome, Latent hyperIgD syndrome, Overt hyperIgD syndrome, Spastic paraplegia, Latent spastic paraplegia, Overt spastic paraplegia, Latent spastic paraplegia with neuropathy, Latent spastic paraplegia with optic atrophy, Latent spastic paraplegia with optic atrophy (dementia) due to neuropathy, Latent dementia, Overt dementia, Familial overt dementia, Retinoblastoma, Latent retinoblastoma, Overt retinoblastoma, Germ cell retinoblastoma, Somatic cell retinoblastoma, Overt germ cell or somatic cell retinoblastoma, Retinoblastoma, Benign retinoblastoma, Pineal tumor, Osteosarcoma, Rod monochromatic vision, Latent rod monochromatic vision, Overt rod monochromatic vision, Achromatopsia Latent achromatopsia, dominant achromatopsia, rod achromatopsia, rod latent achromatopsia, rod dominant achromatopsia, latent rod monochromatic vision or achromatopsia, figure-like malnutrition, latent figure-like malnutrition, dominant figure-like malnutrition, S-cone syndrome, enhanced S-cone syndrome (ESC), latent ESC, dominant ESC, Goldman-Favre syndrome, latent Goldman-Favre syndrome, dominant Goldman-Favre syndrome, Portinia malnutrition, latent Portinia malnutrition, dominant Portinia malnutrition, white spot retinal degeneration, latent white spot retinal degeneration, dominant white spot retinal degeneration, mucosal storage disease type IIIγ, latent mucosal storage disease type IIIγ, dominant mucosal storage disease type IIIγ.Meinzel-Saldino syndrome, recessive Meinzel-Saldino syndrome, dominant Meinzel-Saldino syndrome, pseudoxanthoma elastica, recessive pseudoxanthoma elastica, dominant pseudoxanthoma elastica, Knobloch syndrome, recessive Knobloch syndrome, dominant Knobloch syndrome, foveal dysplasia, recessive foveal dysplasia, dominant foveal dysplasia, anterior segment dysplasia, recessive anterior segment dysplasia, dominant anterior segment dysplasia, foveal dysplasia with anterior segment dysplasia, recessive foveal dysplasia with anterior segment dysplasia, dominant foveal dysplasia with anterior segment dysplasia, spastic ataxia, recessive spastic ataxia, dominant spastic ataxia, Degroove syndrome, Boucher-Neuhauser syndrome, recessive Boucher-Neuhauser syndrome - Neuhauser syndrome, dominant Boucher-Neuhauser syndrome, Boucher-Neuhauser syndrome with choroidal retinal dystrophy, latent Boucher-Neuhauser syndrome with choroidal retinal dystrophy, dominant Boucher-Neuhauser syndrome with choroidal retinal dystrophy, hypopre-β-lipoproteinemia, acanthosis, retinitis pigmentosa, globus pallidus (HARP) degeneration, latent HARP degeneration, dominant HARP degeneration, Hallewarden-Schpattz syndrome, latent Hallewarden-Schpattz syndrome, dominant Hallewarden-Schpattz syndrome, Arager syndrome, latent Arager syndrome, dominant Arager syndrome, polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, early-onset cataract (PH) ARC), latent PHARC, overt PHARC, latent syndromic PHARC, Sotheby's dystrophy, latent Sotheby's dystrophy, overt Sotheby's dystrophy, vitreoretinal dystrophy, latent vitreoretinal dystrophy, overt vitreoretinal dystrophy, optic neuropathy, latent optic neuropathy, overt optic neuropathy, late-onset overt optic neuropathy, orofacial-finger syndrome type 1, Simpson-Goraby-Bemmell syndrome type 2, X-linked retinoschisis, X-linked Oregon ophthalmopathy, X-linked optic atrophy, retinal dysplasia, latent retinal dysplasia, overt retinal dysplasia, X-linked retinal dysplasia, primary X-linked retinal dysplasia X-linked Norrie disease, Coates' disease, X-linked Isle of Ophthalmopathy, Autoimmune Inner Otopathy (AIED), AIED-like diseases, Achoroidal disease, X-linked Achoroidal disease, Neuropathy-Optical Atrophy-Deafness-Retinitis Pigmentosa, X-linked Neuropathy-Optical Atrophy-Deafness-Retinitis Pigmentosa, X-linked Blue Cone Monochromatic Vision, X-linked Red Weakness with Rare Macular Dystrophy Blue Cone Monochromatic Vision (BCM), X-linked Green Weakness with Rare Macular Dystrophy Blue Cone Monochromatic Vision (BCM), Mitochondrial Karnes-Sell Syndrome including Retinitis Pigmentosa, Leigh syndrome, Retinopathy, Mitochondrial Retinitis Pigmentosa with Sensorineural Hearing Loss, Ocular Albinism, Oculocutaneous AlbinismNeuronal ceroid lipofuscin deposition, Zelweg spectrum disorder, cobalamin C deficiency, blue cone monochromatic vision inherited red-green color vision deficiency, blue blindness with yellow-blue color vision deficiency, visual impairment, delayed cone adaptation, uveitis, diabetic retinopathy, diabetic macular edema, persistent corneal epithelial defects, neurotrophic keratitis, herpetic stromal keratitis, chronic dry eye, glaucoma, ocular abrasion, ocular bullae formation, ocular scarring, vision loss, blindness, corneal blindness, dry eye syndrome, aqueous hypoxic dry eye syndrome, Sjögren's syndrome-related aqueous hypoxic dry eye syndrome, non-Sjögren's syndrome-related dry eye syndrome, evaporative dry eye syndrome, meibomian gland dysfunction, blepharitis, blepharitis, ocular erythema acne with atopic dermatitis, aqueous hypoxic dry eye syndrome with evaporative dry eye syndrome, rich in... Fuchs dystrophy, Fuchs endothelial dystrophy (FECD), Fuchs endothelial dystrophy (FED), panuveitis, diffuse uveitis, complete uveitis, cataract, partial cataract, complete cataract, stationary cataract, progressive cataract, hard cataract, soft cataract, nuclear cataract, nuclear sclerotic cataract, cortical cataract, posterior subcapsular cataract, congenital cataract, corneal dystrophy, epithelial with subepithelial dystrophy, epithelial basement membrane dystrophy, recurrent epithelial erosive dystrophy (Francescatti keratopathy, Smorandi dystrophy and / or Helsinglandia dystrophy), subepithelial myxoid keratopathy, Missmann keratopathy, Lich epithelial keratopathy Malnutrition, droplet keratopathy, Bowman's keratopathy, Les-Buckles keratopathy, Thiel-Bunk keratopathy, stromal dystrophy - TGFB1 keratopathy, reticulate keratopathy, reticulate keratopathy type 1 variants (type III, IIIA, I / IIIA, IV), granular keratopathy type 1, granular keratopathy type 2, stromal dystrophy, macular keratopathy, Schneider crystalline keratopathy, congenital stromal keratopathy, punctate keratopathy, amorphous posterior keratopathy, François central cloud keratopathy, Desmi anterior keratopathy, endothelial dystrophy, Fuchs keratopathy, polymorphism Posterior corneal dystrophy, congenital hereditary endothelial dystrophy, X-linked endothelial dystrophy, superficial corneal dystrophy, epithelial basement membrane dystrophy, Missmann juvenile epithelial dystrophy, droplet keratopathy, Lich epithelial dystrophy, subepithelial mucinous keratopathy, Les-Buckles keratopathy, Thiel-Bunk dystrophy, stromal dystrophy, reticular keratopathy, granular keratopathy, macular keratopathy, Schneider crystalline keratopathy, congenital stromal keratopathy, punctate keratopathy, posterior corneal dystrophy, Fuchs dystrophy, polymorphic posterior corneal dystrophy, congenital hereditary endothelial dystrophy, corneal diseases, band keratopathy,Band keratopathy and calcified band keratopathy.

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

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

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

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

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

80. The method according to any one of claims 70-79, wherein the herpesvirus or the pharmaceutical composition is administered to the subject by injection, via injection into the eye, via subretinal injection, via intraocular injection, via intravitreal injection, via suprachoroidal injection, via intraanterior chamber injection, intraocularly, intravitreally, externally, subcutaneously, subconjunctivally, subfascially, intraanterior chamber, retrobulbarly, systemically, extracorporeally, periocularly, near the sclera, anterior near the sclera, posterior near the sclera, orally, peribulbarly, or suprachoroidal.

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

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