Gene therapy for ocular conditions

Abstract

The invention relates to gene therapy of ocular conditions. Described herein are compositions and methods for delivering therapeutic products, such as therapeutic proteins (e.g., antibodies), therapeutic RNAs (e.g., shRNAs, siRNAs, and miRNAs), and therapeutic aptamers, to the retinal / vitreous humor of the eye of a human subject to treat ocular conditions, involving, for example, recombinant viral vectors, such as recombinant adeno-associated virus (rAAV) vectors.

Description

[0001] This application is a divisional of application number 202080041009.0, filed on April 2, 2020, having the title “Gene Therapy of Eye Conditions.” Cross Reference to Related Applications

[0002] This application claims the benefit of the following U.S. provisional patent applications: application number 62 / 828,949, filed on April 3, 2019, application number 62 / 856,533, filed on June 3, 2019, and application number 62 / 946,158, filed on December 10, 2019, which are incorporated by reference herein in their entirety. TECHNICAL FIELD

[0003] Described herein are compositions and methods for delivering therapeutic products, such as therapeutic proteins (e.g., antibodies), therapeutic RNAs (e.g., shRNAs, siRNAs, and miRNAs), and therapeutic aptamers, to the retina / vitreous fluid of the eye of a human subject for the treatment of eye conditions, involving, for example, recombinant viral vectors, such as recombinant adeno-associated viral (rAAV) vectors. BACKGROUND

[0004] The human eye is a highly complex and highly developed sensory organ that is susceptible to many diseases and disorders. Globally, approximately 285 million people have visual impairment, of which 39 million are blind and 246 million have moderate to severe visual impairment (World Health Organization, 2012, “Global Data On Visual Impairments 2010,” Geneva: World Health Organization). Some of the major causes of blindness are cataract (47%), glaucoma (12%), age-related macular degeneration (AMD) (9%), and diabetic retinopathy (5%) (World Health Organization, 2007, “Global Initiative For The Elimination Of Avoidable Blindness: Action Plan 2006-2011,” Geneva: World Health Organization).

[0005] A large number of ocular diseases and diseases in the eye with pathological manifestations can be traced to genetic alterations or protein misregulation (Stone et al., 2017, Ophthalmology 124(9): 1314-1331). Recent advances in genomics and proteomics have had a tremendous impact on the understanding of the underlying disease mechanisms and / or genetic basis of such ocular diseases or manifestations. Gene therapy has been used to treat certain ocular diseases (see, e.g., International Patent Application No. PCT / US2017 / 027650 (International Publication No. WO2017 / 181021 Al)).

[0006] There is a clear unmet medical need for therapies that specifically address underlying genetic abnormalities to treat ocular conditions. SUMMARY

[0007] The present disclosure describes compositions and methods for delivering a therapeutic product, such as a therapeutic protein (e.g., an antibody), a therapeutic RNA (e.g., shRNA, siRNA, and miRNA), and a therapeutic aptamer, to the retina / vitreous humor of an eye of a human subject to treat an ocular condition, involving, e.g., a recombinant viral vector, such as a recombinant adeno-associated viral (rAAV) vector. The therapeutic product can be, e.g., a therapeutic protein (e.g., an antibody), a therapeutic RNA (e.g., shRNA, siRNA, and miRNA), or a therapeutic aptamer. In a particular embodiment, the therapeutic product is a human protein or an antibody against a human protein. Antibodies include, but are not limited to, monoclonal antibodies, polyclonal antibodies, recombinantly produced antibodies, human antibodies, humanized antibodies, chimeric antibodies, synthetic antibodies, tetrameric antibodies comprising two heavy chains and two light chain molecules, antibody light chain monomers, antibody heavy chain monomers, antibody light chain dimers, antibody heavy chain dimers, antibody light chain-heavy chain pairs, intrabodies, heteroconjugate antibodies, monovalent antibodies, antigen-binding fragments of full-length antibodies, and fusion proteins of the foregoing. Such antigen-binding fragments include, but are not limited to, single domain antibodies (variable domains of heavy chain antibodies (VHH) or nanobodies), Fabs, F(ab')2s, and scFv (single chain variable fragments). In particular embodiments, the therapeutic product (e.g., a therapeutic protein) is post-translationally modified. In a particular embodiment, the post-translational modification is specific to the cell type to which the therapeutic product (e.g., a therapeutic protein) is delivered using a particular approach as described herein. Delivery can be accomplished via gene therapy, e.g., by administering a recombinant viral vector or a recombinant DNA expression construct (collectively, “recombinant vectors”) encoding the therapeutic product to the suprachoroidal space, the subretinal space (via vitrectomy or without vitrectomy (e.g., via catheter through the suprachoroidal space or via peripheral injection), the intraretinal space, and / or the exterior surface of the sclera (i.e., juxtascleral administration) of the eye of a human patient to create a permanent reservoir in the eye that continuously supplies the therapeutic product (e.g., a post-translationally modified therapeutic product).

[0008] In one aspect, provided herein is a method for subretinal administration for treating an ocular condition without vitrectomy, comprising administering to a subretinal space in an eye of a human subject in need of treatment a recombinant viral vector comprising a nucleotide sequence encoding a therapeutic product, such that the therapeutic product is expressed and treats the ocular condition, wherein the method does not comprise vitrectomy of the eye of the human patient. In certain embodiments, the administering step comprises administering the recombinant viral vector therapeutic product to the subretinal space of the eye of the human subject via a suprachoroidal space of the eye of the human subject. In certain embodiments, the administering step is by use of a subretinal drug delivery device comprising a catheter that can be inserted through and toward the posterior pole of the suprachoroidal space, with a small needle tip injected into the subretinal space at the posterior pole. In certain embodiments, the administering step comprises inserting the catheter of the subretinal drug delivery device through the suprachoroidal space.

[0009] In another aspect, provided herein is a method for treating an ocular condition, comprising administering to a subretinal space in an eye of a human subject in need of treatment a recombinant viral vector comprising a nucleotide sequence encoding a therapeutic product, such that the therapeutic product is expressed and treats the ocular condition, wherein the method does not comprise vitrectomy of the eye of the human patient. In certain embodiments, the administering step comprises administering the recombinant viral vector therapeutic product to the subretinal space of the eye of the human subject via a suprachoroidal space of the eye of the human subject. In certain embodiments, the administering step is by use of a subretinal drug delivery device comprising a catheter that can be inserted through and toward the posterior pole of the suprachoroidal space, with a small needle tip injected into the subretinal space at the posterior pole. In certain embodiments, the administering step comprises inserting the catheter of the subretinal drug delivery device through the suprachoroidal space.

[0010] In one aspect, provided herein is a method for subretinal administration for treating an ocular condition without vitrectomy, comprising administering to a subretinal space in an eye of a human subject in need of treatment a recombinant viral vector comprising a nucleotide sequence encoding a therapeutic product, such that the therapeutic product is expressed and treats the ocular condition, wherein the method does not comprise vitrectomy of the eye of the human patient. In certain embodiments, the administering step comprises administering the recombinant viral vector therapeutic product to the subretinal space of the eye of the human subject via a suprachoroidal space of the eye of the human subject. In certain embodiments, the administering step is by use of a subretinal drug delivery device comprising a catheter that can be inserted through and toward the posterior pole of the suprachoroidal space, with a small needle tip injected into the subretinal space at the posterior pole. In certain embodiments, the administering step comprises inserting the catheter of the subretinal drug delivery device through the suprachoroidal space.

[0011] In another aspect, provided herein is a method for treating an ocular condition, comprising administering to a subretinal space in an eye of a human subject in need of treatment a recombinant viral vector comprising a nucleotide sequence encoding a therapeutic product, such that the therapeutic product is expressed and treats the ocular condition, wherein the method does not comprise vitrectomy of the eye of the human patient. In certain embodiments, the administering step comprises administering the recombinant viral vector therapeutic product to the subretinal space of the eye of the human subject via a suprachoroidal space of the eye of the human subject. In certain embodiments, the administering step is by use of a subretinal drug delivery device comprising a catheter that can be inserted through and toward the posterior pole of the suprachoroidal space, with a small needle tip injected into the subretinal space at the posterior pole. In certain embodiments, the administering step comprises inserting the catheter of the subretinal drug delivery device through the suprachoroidal space.

[0012] In one aspect, provided herein is a method for treating an ocular condition suprachoroidally, comprising administering to the suprachoroidal space of an eye of a human subject in need of treatment a recombinant viral vector comprising a nucleotide sequence encoding a therapeutic product, such that the therapeutic product is expressed and treats the ocular condition. In certain embodiments, the administering step is by injection of the recombinant viral vector into the suprachoroidal space using a suprachoroidal drug delivery device. In certain embodiments, the suprachoroidal drug delivery device is a microinjector.

[0013] In another aspect, provided herein is a method for treating an ocular condition, comprising administering to the suprachoroidal space of an eye of a human subject in need of treatment a recombinant viral vector comprising a nucleotide sequence encoding a therapeutic product, such that the therapeutic product is expressed and treats the ocular condition. In certain embodiments, the administering step is by injection of the recombinant viral vector into the suprachoroidal space using a suprachoroidal drug delivery device. In certain embodiments, the suprachoroidal drug delivery device is a microinjector.

[0014] In certain embodiments, delivery to the subretinal space or suprachoroidal space can be performed using the methods and / or devices described and disclosed in International Publication Nos. WO 2016 / 042162, WO 2017 / 046358, WO 2017 / 158365, and WO 2017 / 158366, each of which is incorporated by reference herein in its entirety.

[0015] In one aspect, provided herein is a method for treating an ocular condition suprachoroidally, comprising administering to the suprachoroidal space of an eye of a human subject in need of treatment a recombinant viral vector comprising a nucleotide sequence encoding a therapeutic product, such that the therapeutic product is expressed and treats the ocular condition. In certain embodiments, the administering step is by injection of the recombinant viral vector into the suprachoroidal space using a suprachoroidal drug delivery device. In certain embodiments, the suprachoroidal drug delivery device is a microinjector.

[0016] In another aspect, provided herein is a method for treating an ocular condition, comprising administering to the suprachoroidal space of an eye of a human subject in need of treatment a recombinant viral vector comprising a nucleotide sequence encoding a therapeutic product, such that the therapeutic product is expressed and treats the ocular condition. In certain embodiments, the administering step is by injection of the recombinant viral vector into the suprachoroidal space using a suprachoroidal drug delivery device. In certain embodiments, the suprachoroidal drug delivery device is a microinjector.

[0017] In certain embodiments, the therapeutic product is not an anti-human vascular endothelial growth factor (hVEGF) antibody.

[0018] In certain embodiments, the ocular condition is not associated with neovascular age-related macular degeneration (nAMD), also known as the "wet" neovascular form of AMD ("WAMD" or "wet AMD").

[0019] In certain embodiments, the therapeutic product is an anti-hVEGF antibody.

[0020] In certain embodiments, the ocular condition is associated with nAMD.

[0021] In certain embodiments, the ocular condition is associated with nAMD, and the therapeutic product is an anti-hVEGF antibody.

[0022] In certain embodiments, the therapeutic product is not an anti-human vascular endothelial growth factor (hVEGF) antibody.

[0023] In certain embodiments, the ocular condition is not associated with neovascular age-related macular degeneration (nAMD), also known as the "wet" neovascular form of AMD ("WAMD" or "wet AMD").

[0024] In one aspect, provided herein is a method for treating an ocular condition by subretinal administration, comprising administering a recombinant viral vector comprising a nucleotide sequence encoding a therapeutic product to the subretinal space of the posterior of the eye of a human subject in need of treatment, such that the therapeutic product is expressed and the ocular condition is treated, wherein the method does not comprise performing a vitrectomy on the eye of the human patient. In certain embodiments, the injecting step is by intravitreal injection. In certain embodiments, the method of intravitreal administration results in uniform expression of the therapeutic product throughout the eye (e.g., less than 5%, 10%, 20%, 30%, 40%, or 50% variation in expression at the site of injection compared to the amount of expression in other regions of the eye). In certain embodiments, the intravitreal injection comprises inserting a sharp needle into the sclera via the superior or inferior side of the eye and passing the sharp needle completely through the vitreous body to inject the recombinant viral vector into the subretinal space on the other side. In certain embodiments, the needle is inserted at the 2 o'clock or 10 o'clock position. In certain embodiments, the intravitreal injection comprises inserting a trocar into the sclera and inserting a cannula through the trocar and through the vitreous body to inject the recombinant viral vector into the subretinal space on the other side. In certain embodiments, the therapeutic product is an anti-hVEGF antibody. In certain embodiments, the anti-hVEGF antibody is an anti-hVEGF antigen-binding fragment. In certain embodiments, the anti-hVEGF antigen-binding fragment is a Fab, F(ab')2, or single chain variable fragment (scFv). In certain embodiments, the anti-hVEGF antibody contains a heavy chain comprising the amino acid sequence of SEQ ID NO: 2 or SEQ ID NO: 4 and a light chain comprising the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 3. In certain embodiments, wherein the anti-hVEGF antibody comprises light chain CDRs 1-3 of SEQ ID NO: 14-16 and heavy chain CDRs 1-3 of SEQ ID NO: 17-19 or SEQ ID NO: 20, 18, and 21. In certain embodiments, wherein the ocular condition is associated with nAMD, dry age-related macular degeneration (dry AMD), retinal vein occlusion (RVO), diabetic macular edema (DME), or diabetic retinopathy (DR). In certain embodiments, the ocular condition is associated with nAMD.

[0025] In another aspect, provided herein is a method for treating an eye condition comprising administering to the subretinal space of the posterior of the eye of a human subject in need of treatment a recombinant viral vector comprising a nucleotide sequence encoding a therapeutic product, such that the therapeutic product is expressed and the eye condition is treated, wherein the method does not comprise performing a vitrectomy on the eye of the human patient. In certain embodiments, the step of injecting is by intravitreal injection. In certain embodiments, the method of intravitreal administration results in uniform expression of the therapeutic product throughout the eye (e.g., less than 5%, 10%, 20%, 30%, 40%, or 50% variation in expression at the site of injection compared to the amount of expression in other regions of the eye). In certain embodiments, the intravitreal injection comprises inserting a sharp needle into the sclera via the superior or inferior side of the eye and passing the sharp needle completely through the vitreous body to inject the recombinant viral vector into the subretinal space on the other side. In certain embodiments, the needle is inserted at the 2 o'clock or 10 o'clock position. In certain embodiments, the intravitreal injection comprises inserting a trocar into the sclera and inserting a cannula through the trocar and through the vitreous body to inject the recombinant viral vector into the subretinal space on the other side. In certain embodiments, the therapeutic product is an anti-hVEGF antibody. In certain embodiments, the anti-hVEGF antibody is an anti-hVEGF antigen-binding fragment. In certain embodiments, the anti-hVEGF antigen-binding fragment is a Fab, F(ab')2, or single chain variable fragment (scFv). In certain embodiments, the anti-hVEGF antibody contains a heavy chain comprising the amino acid sequence of SEQ ID NO: 2 or SEQ ID NO: 4 and a light chain comprising the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 3. In certain embodiments, wherein the anti-hVEGF antibody comprises light chain CDRs 1-3 of SEQ ID NOs: 14-16 and heavy chain CDRs 1-3 of SEQ ID NOs: 17-19 or SEQ ID NOs: 20, 18, and 21. In certain embodiments, wherein the eye condition is associated with nAMD, dry age-related macular degeneration (dry AMD), retinal vein occlusion (RVO), diabetic macular edema (DME), or diabetic retinopathy (DR). In certain embodiments, the eye condition is associated with nAMD.

[0026] In certain embodiments of the methods described herein, (1) the ocular condition is associated with Batten-CLN1 and the therapeutic product is palmitoyl-protein thioesterase 1 (PPT1); (2) the ocular condition is associated with Batten-CLN2 and the therapeutic product is tripeptidyl- peptidase 1 (TPP1); (3) the ocular condition is associated with Batten-CLN3 and the therapeutic product is Battenin (CLN3); (4) the ocular condition is associated with Batten-CLN6 and the therapeutic product is CLN6 transmembrane ER protein (CLN6); (5) the ocular condition is associated with Batten-CLN7 and the therapeutic product is major facilitator superfamily domain containing 8 (MFSD8); (6) the ocular condition is associated with Usher's-Type 1 and the therapeutic product is myosin VIIA (MY07A); (7) the ocular condition is associated with Usher's-Type 1 and the therapeutic product is cadherin-related 23 (CDH23); (8) the ocular condition is associated with Usher's-Type 2 and the therapeutic product is protocadherin-related 15 (PCDH15); (9) the ocular condition is associated with Usher's-Type 2 and the therapeutic product is Usherin (USH2A); (10) the ocular condition is associated with Usher's-Type 3 and the therapeutic product is Clarin 1 (CLRN1); (11) the ocular condition is associated with Stargardt's and the therapeutic product is ATP binding cassette subfamily A member 4 (ABCA4); (12) the ocular condition is associated with Stargardt's and the therapeutic product is ELOVL fatty acid elongase 4 (ELOVL4); (13) the ocular condition is associated with uveitis and the therapeutic product is an anti- interleukin 6 (IL6) monoclonal antibody; (14) the ocular condition is associated with uveitis and the therapeutic product is an anti-TNF-a (TNF) monoclonal antibody; (15) the ocular condition is associated with diabetic macular edema (DME) and the therapeutic product is an anti-IL6 monoclonal antibody; (16) the ocular condition is associated with red-green color blindness and the therapeutic product is L opsin (OPN1LW); (17) the ocular condition is associated with red-green color blindness and the therapeutic product is M opsin (OPN1MW); (18) the ocular condition is associated with blue cone monochromacy and the therapeutic product is M opsin (OPN1MW); (19) the ocular condition is associated with Leber congenital amaurosis-1 (LCA 1) and the therapeutic product is retinal guanylate cyclase 2D (GUCY2D); (20) the ocular condition is associated with Leber congenital amaurosis-2 (LCA 2) and the therapeutic product is retinoid isomerohydrolase RPE65 (RPE65); (21) the ocular condition is associated with LCA 3 and the therapeutic product is spermatogenesis associated 7 (SPATA7);(22) the ocular condition is associated with Leber congenital amaurosis 4 (LCA 4) and the therapeutic product is aryl hydrocarbon receptor interacting protein-like 1 (AIPL1); (23) the ocular condition is associated with Leber congenital amaurosis 5 (LCA 5) and the therapeutic product is Lebercilin (LCA5); (24) the ocular condition is associated with Leber congenital amaurosis 6 (LCA 6) and the therapeutic product is RPGR interacting protein 1 (RPGRIP1); (25) the ocular condition is associated with Leber congenital amaurosis 7 (LCA 7) and the therapeutic product is cone-rod homeobox (CRX); (26) the ocular condition is associated with Leber congenital amaurosis 8 (LCA 8) and the therapeutic product is Crumbs cell polarity complex component 1 (CRB1) (also known as LCA8); (27) the ocular condition is associated with Leber congenital amaurosis 9 (LCA 9) and the therapeutic product is nicotinamide nucleotide adenylyltransferase 1 (NMNAT1); (28) the ocular condition is associated with Leber congenital amaurosis 10 (LCA 10) and the therapeutic product is centrosomal protein 290 (CEP290); (29) the ocular condition is associated with Leber congenital amaurosis 11 (LCA 11) and the therapeutic product is inosine monophosphate dehydrogenase 1 (IMPDH1); (30) the ocular condition is associated with Leber congenital amaurosis 12 (LCA 12) and the therapeutic product is retinal degeneration 3, GUCY2D regulator (RD3); (31) the ocular condition is associated with Leber congenital amaurosis 13 (LCA 13) and the therapeutic product is retinol dehydrogenase 12 (RDH12); (32) the ocular condition is associated with Leber congenital amaurosis 14 (LCA 14) and the therapeutic product is lecithin retinol acyltransferase (LRAT); (33) the ocular condition is associated with Leber congenital amaurosis 15 (LCA 15) and the therapeutic product is tubby-like protein 1 (TULP1); (34) the ocular condition is associated with Leber congenital amaurosis 16 (LCA 16) and the therapeutic product is potassium voltage-gated channel subfamily J member 13 (KCNJ13); (35) the ocular condition is associated with Leber’s hereditary optic neuropathy (LHON) and the therapeutic product is mitochondrially encoded NADH dehydrogenase 1 (MT-ND1); (36) the ocular condition is associated with LHON and the therapeutic product is mitochondrially encoded NADH dehydrogenase 4 (MT-ND4); (37) the ocular condition is associated with LHON and the therapeutic product is mitochondrially encoded NADH dehydrogenase 6 (MT-ND6);(38) the eye condition is associated with neuromyelitis optica (NMO) and the therapeutic product is an anti-complement antibody or anti-complement aptamer, wherein the anti-complement monoclonal antibody or aptamer is an anti-complement Cl antibody or aptamer, an anti-complement Clq monoclonal antibody or aptamer, an anti-complement Cls monoclonal antibody or aptamer, an anti-complement C2 monoclonal antibody or aptamer, an anti-complement C2a monoclonal antibody or aptamer, an anti-complement C2b monoclonal antibody or aptamer, an anti-complement C3 monoclonal antibody or aptamer, an anti-complement C3a monoclonal antibody or aptamer, an anti-complement C3b monoclonal antibody or aptamer, an anti-complement C4 monoclonal antibody or aptamer, an anti-complement C4a monoclonal antibody or aptamer, an anti-complement C4b monoclonal antibody or aptamer, an anti-complement C5 monoclonal antibody or aptamer, an anti-complement C5a monoclonal antibody or aptamer, an anti-complement C5b monoclonal antibody or aptamer, an anti-complement C6 monoclonal antibody or aptamer, an anti-complement C7 monoclonal antibody or aptamer, an anti-complement C8 monoclonal antibody or aptamer, or an anti-complement C9 monoclonal antibody or aptamer, or preferably an anti-complement C5 antibody; (39) the eye condition is associated with NMO and the therapeutic product is an anti-IL6 monoclonal antibody or aptamer; (40) the eye condition is associated with uveitis and the therapeutic product is an anti-complement monoclonal antibody or aptamer, wherein the anti-complement monoclonal antibody or aptamer is an anti-complement Cl monoclonal antibody or aptamer, an anti-complement Clq monoclonal antibody or aptamer, an anti-complement Cls monoclonal antibody or aptamer, an anti-complement C2 monoclonal antibody or aptamer, an anti-complement C2a monoclonal antibody or aptamer, an anti-complement C2b monoclonal antibody or aptamer, an anti-complement C3 monoclonal antibody or aptamer, an anti-complement C3a monoclonal antibody or aptamer, an anti-complement C3b monoclonal antibody or aptamer, an anti-complement C4 monoclonal antibody or aptamer, an anti-complement C4a monoclonal antibody or aptamer, an anti-complement C4b monoclonal antibody or aptamer, an anti-complement C5 monoclonal antibody or aptamer, an anti-complement C5a monoclonal antibody or aptamer, an anti-complement C5b monoclonal antibody or aptamer, an anti-complement C6 monoclonal antibody or aptamer, an anti-complement C7 monoclonal antibody or aptamer, an anti-complement C8 monoclonal antibody or aptamer, or an anti-complement C9 monoclonal antibody or aptamer, or preferably an anti-complement C5 antibody; (41) the eye condition is associated with uveitis and the therapeutic product is angiotensin I converting enzyme (ACE); (42) the eye condition is associated with uveitis and the therapeutic product is interleukin 10 (IL10); (43) the eye condition is associated with uveitis and the therapeutic product is an anti-TNF monoclonal antibody; (44) the eye condition is associated with choroideremia and the therapeutic product is Rab chaperone 1 (CHM); (45) the eye condition is associated with X-linked retinoschisis (XLRS) and the therapeutic product is retinoschisin (RS1); (46) the eye condition is associated with Bardet-Biedl syndrome 1 (BBS1) and the therapeutic product is Bardet-Biedl syndrome 1 (BBS1);(47) the eye condition is associated with Bardet-Biedl Syndrome 2, and the therapeutic product is Bardet-Biedl Syndrome 2 (BBS2); (48) the eye condition is associated with Bardet-Biedl Syndrome 3, and the therapeutic product is ADP ribosylation factor-like GTPase 6 (ARL6) (also known as BBS3); (49) the eye condition is associated with Bardet-Biedl Syndrome 4, and the therapeutic product is Bardet-Biedl Syndrome 4 (BBS4); (50) the eye condition is associated with Bardet-Biedl Syndrome 5, and the therapeutic product is Bardet-Biedl Syndrome 5 (BBS5); (51) the eye condition is associated with Bardet-Biedl Syndrome 6, and the therapeutic product is McKusick-Kaufman Syndrome (MKKS), also known as BBS6; (52) the eye condition is associated with Bardet-Biedl Syndrome 7, and the therapeutic product is Bardet-Biedl Syndrome 7 (BBS7); (53) the eye condition is associated with Bardet-Biedl Syndrome 8, and the therapeutic product is tetratricopeptide repeat domain 8 (TTC8), also known as BBS8; (54) the eye condition is associated with Bardet-Biedl Syndrome 9, and the therapeutic product is Bardet-Biedl Syndrome 9 (BBS9); (55) the eye condition is associated with Bardet-Biedl Syndrome 10, and the therapeutic product is Bardet-Biedl Syndrome 10 (BBS10); (56) the eye condition is associated with Bardet-Biedl Syndrome 11, and the therapeutic product is tripartite motif-containing 32 (TRIM32), also known as BBS11; (57) the eye condition is associated with Bardet-Biedl Syndrome 12, and the therapeutic product is Bardet-Biedl Syndrome 12 (BBS12); (58) the eye condition is associated with Bardet-Biedl Syndrome 13, and the therapeutic product is MKS transition zone complex subunit 1 (MKS1), also known as BBS13; (59) the eye condition is associated with Bardet-Biedl Syndrome 14, and the therapeutic product is centrosomal protein 290 (CEP290), also known as BBS14 and LCA10; (60) the eye condition is associated with Bardet-Biedl Syndrome 15, and the therapeutic product is WD repeat-containing planar cell polarity effector (WDPCP), also known as BBS15; (61) the eye condition is associated with Bardet-Biedl Syndrome 16, and the therapeutic product is serologically defined colon cancer antigen 8 (SDCCAG8), also known as BBS16; (62) the eye condition is associated with Bardet-Biedl Syndrome 17, and the therapeutic product is leucine zipper transcription factor-like 1 (LZTFL1), also known as BBS17; (63) the eye condition is associated with Bardet-Biedl Syndrome 18, and the therapeutic product is BBSome interacting protein 1 (BBIP1), also known as BBS18;(64) the eye condition is associated with Bardet-Biedl Syndrome 19 and the therapeutic product is Intraflagellar Transport Protein 27 (IFT27), also known as BBS19; (65) the eye condition is associated with Cone Dystrophy and the therapeutic product is Guanylate Cyclase Activator 1A (GUCA1A); (66) the eye condition is associated with Optic Nerve Atrophy and the therapeutic product is OPA1 Mitochondrial Motor Protein-Like GTPase (OPA1); (67) the eye condition is associated with Retinitis Pigmentosa 1 and the therapeutic product is RP1 Axon Microtubule-Associated (RP1); (68) the eye condition is associated with Retinitis Pigmentosa 2 and the therapeutic product is RP2 Activator of ARL3 GTPase (RP2); (69) the eye condition is associated with Retinitis Pigmentosa 7 and the therapeutic product is Peripherin 2 (PRPH2); (70) the eye condition is associated with Retinitis Pigmentosa 11 and the therapeutic product is Pre-mRNA Processing Factor 31 (PRPF31); (71) the eye condition is associated with Retinitis Pigmentosa 12 and the therapeutic product is Crumbs Cell Polarity Complex Component 1 (CRB1), also known as LCA8; (72) the eye condition is associated with Retinitis Pigmentosa 13 and the therapeutic product is Pre-mRNA Processing Factor 8 (PRPF8); (73) the eye condition is associated with Retinitis Pigmentosa 25 and the therapeutic product is Eyes Shut Homolog (EYS); (74) the eye condition is associated with Retinitis Pigmentosa 28 and the therapeutic product is FAM161 Centrosomal Protein A (FAM161A); (75) the eye condition is associated with Retinitis Pigmentosa 37 and the therapeutic product is Nuclear Receptor Subfamily 2, Group E, Member 3 (NR2E3); (76) the eye condition is associated with Retinitis Pigmentosa 38 and the therapeutic product is MER Proto-Oncogene Tyrosine Kinase (MERTK); (77) the eye condition is associated with Retinitis Pigmentosa 40 and the therapeutic product is Phosphodiesterase 6B (PDE6B); (78) the eye condition is associated with Retinitis Pigmentosa 41 and the therapeutic product is Prominin 1 (PROM1); (79) the eye condition is associated with Retinitis Pigmentosa 43 and the therapeutic product is Phosphodiesterase 6A (PDE6A); (80) the eye condition is associated with Retinitis Pigmentosa 56 and the therapeutic product is Interphotoreceptor Matrix Proteoglycan 2 (IMPG2); (81) the eye condition is associated with Retinitis Pigmentosa 62 and the therapeutic product is Male Germ Cell Associated Kinase (MAK); (82) the eye condition is associated with Retinitis Pigmentosa 80 and the therapeutic product is Intraflagellar Transport Protein 140 (IFT140);(83) the eye condition is associated with dry AMD and the therapeutic product is an anti-complement monoclonal antibody or aptamer, wherein the anti-complement monoclonal antibody or aptamer is an anti-complement Cl monoclonal antibody or aptamer, an anti-complement Clq monoclonal antibody or aptamer, an anti-complement Cls monoclonal antibody or aptamer, an anti-complement C2 monoclonal antibody or aptamer, an anti-complement C2a monoclonal antibody or aptamer, an anti-complement C2b monoclonal antibody or aptamer, an anti-complement C3 monoclonal antibody or aptamer, an anti-complement C3a monoclonal antibody or aptamer, an anti-complement C3b monoclonal antibody or aptamer, an anti-complement C4 monoclonal antibody or aptamer, an anti-complement C4a monoclonal antibody or aptamer, an anti-complement C4b monoclonal antibody or aptamer, an anti-complement C5 monoclonal antibody or aptamer, an anti-complement C5a monoclonal antibody or aptamer, an anti-complement C5b monoclonal antibody or aptamer, an anti-complement C6 monoclonal antibody or aptamer, an anti-complement C7 monoclonal antibody or aptamer, an anti-complement C8 monoclonal antibody or aptamer, or an anti-complement C9 monoclonal antibody or aptamer, or preferably an anti-complement C5 antibody; (84) the eye condition is associated with dry AMD and the therapeutic product is an anti- membrane attack complex (MAC) therapeutic product, preferably the anti-MAC therapeutic product is an anti-MAC monoclonal antibody, which is a monoclonal antibody against the human proteins that make up the membrane attack complex, which are four complement proteins C5b (SEQ ID NO. 314-316), C6 (SEQ ID NO. 317), C7 (SEQ ID NO. 318), and C8 (SEQ ID NO. 319-321); (85) the eye condition is associated with dry AMD and the therapeutic product is HtrA serine peptidase 1 (HTRA1); (86) the eye condition is associated with Best disease and the therapeutic product is Bestrophin 1 (BEST1); (87) the eye condition is associated with dry AMD and the therapeutic product is a complement factor B antisense oligonucleotide; (88) the eye condition is associated with dry AMD and the therapeutic product is an anti-beta-amyloid monoclonal antibody; (89) the eye condition is associated with dry AMD and the therapeutic product is CD59 glycoprotein (CD59); (90) the eye condition is associated with dry AMD and the therapeutic product is Channelrhodopsin-1 (ChRl), which includes the human homolog of ChRl; (91) the eye condition is associated with dry AMD and the therapeutic product is Channelrhodopsin-2 (ChR2), which includes the human homolog of ChR2;(92) the eye condition is associated with dry AMD and the therapeutic product is an anti-complement monoclonal antibody or aptamer, wherein the anti-complement monoclonal antibody or aptamer is an anti-complement Cl monoclonal antibody or aptamer, an anti-complement Clq monoclonal antibody or aptamer, an anti-complement Cls monoclonal antibody or aptamer, an anti-complement C2 monoclonal antibody or aptamer, an anti-complement C2a monoclonal antibody or aptamer, an anti-complement C2b monoclonal antibody or aptamer, an anti-complement C3 monoclonal antibody or aptamer, an anti-complement C3a monoclonal antibody or aptamer, an anti-complement C3b monoclonal antibody or aptamer, an anti-complement C4 monoclonal antibody or aptamer, an anti-complement C4a monoclonal antibody or aptamer, an anti-complement C4b monoclonal antibody or aptamer, an anti-complement C5 monoclonal antibody or aptamer, an anti-complement C5a monoclonal antibody or aptamer, an anti-complement C5b monoclonal antibody or aptamer, an anti-complement C6 monoclonal antibody or aptamer, an anti-complement C7 monoclonal antibody or aptamer, an anti-complement C8 monoclonal antibody or aptamer, or an anti-complement C9 monoclonal antibody or aptamer, or preferably an anti-complement C5 antibody; (93) the eye condition is associated with dry AMD and the therapeutic product is an anti-complement factor D therapeutic product, including but not limited to an anti-complement factor D monoclonal antibody or an anti-complement factor D aptamer; (94) the eye condition is associated with age-related retinal ganglion cell (RGC) degeneration and the therapeutic product is DnaJ heat shock protein family (Hsp40) member C3 (DNAJC3), also known as P58IPK; (95) the eye condition is associated with blue cone monochromacy (BCM) and the therapeutic product is L opsin (OPN1MW); (96) the eye condition is associated with glaucoma and the therapeutic product is beta-2 adrenergic receptor siRNA; (97) the eye condition is associated with glaucoma and the therapeutic product is caspase-2 (CASP2); (98) the eye condition is associated with glaucoma and the therapeutic product is insulin receptor substrate 1 (IRS1); (99) the eye condition is associated with glaucoma and the therapeutic product is HIF-1 responsive protein RTP801 (RTP801); (100) the eye condition is associated with glaucoma and the therapeutic product is transforming growth factor beta 2 (TGFB2); (101) the eye condition is associated with glaucoma and the therapeutic product is brain-derived neurotrophic factor (BDNF); (102) the eye condition is associated with glaucoma and the therapeutic product is ciliary neurotrophic factor (CNTF); (103) the eye condition is associated with glaucoma and the therapeutic product is prostaglandin endoperoxide synthase 2 (PTGS2); (104) the eye condition is associated with glaucoma and the therapeutic product is prostaglandin F receptor (PTGFR) (when the eye condition is associated with glaucoma, in a particular embodiment, a recombinant viral vector comprising a nucleotide sequence encoding PTGFR can be administered to a human subject in combination with a recombinant viral vector comprising a nucleotide sequence encoding PTGS2;In another particular embodiment, the recombinant viral vector can be administered to a human subject comprising a nucleotide sequence encoding PTGFR and a nucleotide sequence encoding PTGS2; (105) the ocular condition is associated with glaucoma and the therapeutic product is hyaluronidase, such as HYAL1, HYAL2, HYAL3, HYAL4, and HYAL5; (106) the ocular condition is associated with glaucoma and the therapeutic product is pigment epithelium-derived factor (PEDF); (107) the ocular condition is associated with glaucoma and the therapeutic product is vascular endothelial growth factor (VEGF); (108) the ocular condition is associated with glaucoma and the therapeutic product is placental growth factor (PGF), wherein PGF can be used in combination with VEGF; (109) the ocular condition is associated with glaucoma (such as congenital glaucoma or juvenile glaucoma) and the therapeutic product is myocilin (MYOC); (110) the ocular condition is associated with NMO and the therapeutic product is an anti-complement C5 monoclonal antibody; (111) the ocular condition is associated with NMO and the therapeutic product is C-C motif chemokine receptor 5 (CCR5) siRNA, CCR5 shRNA, siRNA, or CCR5 miRNA (preferably, CCR5 miRNA); (112) the ocular condition is associated with NMO and the therapeutic product is an anti-CD19 monoclonal antibody; (113) the ocular condition is associated with retinitis pigmentosa associated with mutations in rhodopsin and the therapeutic product is channelrhodopsin-1 (ChRl), which includes human homologs of ChRl; (114) the ocular condition is associated with retinitis pigmentosa associated with mutations in rhodopsin and the therapeutic product is channelrhodopsin-2 (ChR2), which includes human homologs of ChR2; (115) the ocular condition is associated with retinitis pigmentosa and the therapeutic product is ciliary neurotrophic factor (CNTF); (116) the ocular condition is associated with autosomal recessive retinitis pigmentosa and the therapeutic product is Crumbs cell polarity complex component 1 (CRB1); (117) the ocular condition is associated with autosomal recessive retinitis pigmentosa and the therapeutic product is Crumbs cell polarity complex component 2 (CRB2); (118) the ocular condition is associated with retinitis pigmentosa and the therapeutic product is histone deacetylase 4 (HDAC4); (119) the ocular condition is associated with retinitis pigmentosa and the therapeutic product is rhodopsin (RHO); (120) the ocular condition is associated with retinitis pigmentosa and the therapeutic product is nerve growth factor (NGF); (121) the ocular condition is associated with retinitis pigmentosa and the therapeutic product is nuclear factor erythroid 2-like 2 (NRF2); (122) the ocular condition is associated with retinitis pigmentosa and the therapeutic product is pigment epithelium-derived factor (PEDF);(123) the eye condition is associated with retinitis pigmentosa and the therapeutic product is glutathione S-transferase PI 1 (GSTP1), also known as PI; (124) the eye condition is associated with retinitis pigmentosa and the therapeutic product is rod-derived cone viability factor (RDCVF); (125) the eye condition is associated with retinitis pigmentosa and the therapeutic product is rhodopsin (RHO); (126) the eye condition is associated with retinitis pigmentosa and the therapeutic product is retinal lecithin retinol binding protein 1 (RLBP1); (127) the eye condition is associated with Stargardt disease and the therapeutic product is an anti-complement C5 aptamer; (128) the eye condition is associated with uveitis and the therapeutic product is double homeobox 4 (DUX4); (129) the eye condition is associated with uveitis and the therapeutic product is NLR family, pyrin domain containing 3 (NLRP3); (130) the eye condition is associated with uveitis and the therapeutic product is spleen associated tyrosine kinase (SYK); (131) the eye condition is associated with uveitis and the therapeutic product is adrenocorticotropic hormone (ACTH); (132) the eye condition is associated with uveitis and the therapeutic product is caspase 1 (CASP1); (133) the eye condition is associated with uveitis and the therapeutic product is an anti-CD59 therapeutic product (such as an anti-CD59 therapeutic protein (e.g., an anti-CD59 monoclonal antibody), or an anti-CD59 therapeutic RNA (e.g., an anti-CD59 shRNA, an anti-CD59 siRNA, or an anti-CD59 miRNA), preferably an anti-CD59 monoclonal antibody); (134) the eye condition is associated with uveitis and the therapeutic product is an anti-complement monoclonal antibody or aptamer, wherein the anti-complement monoclonal antibody or aptamer is an anti-complement Cl monoclonal antibody or aptamer, an anti-complement Clq monoclonal antibody or aptamer, an anti-complement Cls monoclonal antibody or aptamer, an anti-complement C2 monoclonal antibody or aptamer, an anti-complement C2a monoclonal antibody or aptamer, an anti-complement C2b monoclonal antibody or aptamer, an anti-complement C3 monoclonal antibody or aptamer, an anti-complement C3a monoclonal antibody or aptamer, an anti-complement C3b monoclonal antibody or aptamer, an anti-complement C4 monoclonal antibody or aptamer, an anti-complement C4a monoclonal antibody or aptamer, an anti-complement C4b monoclonal antibody or aptamer, an anti-complement C5 monoclonal antibody or aptamer, an anti-complement C5a monoclonal antibody or aptamer, an anti-complement C5b monoclonal antibody or aptamer, an anti-complement C6 monoclonal antibody or aptamer, an anti-complement C7 monoclonal antibody or aptamer, an anti-complement C8 monoclonal antibody or aptamer, or an anti-complement C9 monoclonal antibody or aptamer, or preferably an anti-complement C5 antibody; (135) the eye condition is associated with corneal neovascularization and the therapeutic product is insulin receptor substrate 1 (IRS1); (136) the eye condition is associated with corneal neovascularization and the therapeutic product is NOTCH regulated ankyrin repeat protein (NRARP);(137) the eye condition is associated with diabetic retinopathy and the therapeutic product is a NOTCH modulated ankyrin repeat protein (NRARP); (138) the eye condition is associated with diabetic retinopathy and the therapeutic product is alpha-2-antiplasmin (A2AP); (139) the eye condition is associated with diabetic retinopathy and the therapeutic product is plasminogen (PLG); (140) the eye condition is associated with diabetic retinopathy and the therapeutic product can be growth hormone; (141) the eye condition is associated with diabetic retinopathy and the therapeutic product is insulin-like growth factor 1 (IGF1), wherein IGF1 can be used in combination with growth hormone; (142) the eye condition is associated with diabetic retinopathy and the therapeutic product is interleukin 1 beta (IL1B); (143) the eye condition is associated with diabetic retinopathy and the therapeutic product is angiotensin I converting enzyme 2 (ACE2), wherein ACE2 can be used in combination with IL1B; (144) the eye condition is associated with diabetic retinopathy and the therapeutic product is IRS1; (145) the eye condition is associated with diabetic retinopathy and the therapeutic product is an anti-integrin oligopeptide; (146) the eye condition is associated with diabetic retinopathy and the therapeutic product is an anti- placental growth factor (PGF) monoclonal antibody; (147) the eye condition is associated with Graves' ophthalmopathy (also known as Graves' orbitopathy) and the therapeutic product is an anti-CD40 monoclonal antibody; (148) the eye condition is associated with Graves' ophthalmopathy and the therapeutic product is an anti-insulin-like growth factor 1 receptor (IGF1R) monoclonal antibody; (149) the eye condition is associated with Graves' ophthalmopathy and the therapeutic product is an anti-insulin-like growth factor 2 receptor (IGF2R) monoclonal antibody; (150) the eye condition is associated with DME and the therapeutic product is an anti-integrin oligopeptide; (151) the eye condition is associated with DME and the therapeutic product is an anti-placental growth factor (PGF) monoclonal antibody; (152) the eye condition is associated with DME and the therapeutic product is an RTP801 siRNA; (153) the eye condition is associated with vision loss associated with multiple sclerosis (MS) and the therapeutic product is ND1; (154) the eye condition is associated with myopia and the therapeutic product is matrix metalloproteinase 2 (MMP2) RNAi; (155) the eye condition is associated with X-linked recessive ocular albinism and the therapeutic product is G protein-coupled receptor 143 (GPR143); (156) the eye condition is associated with ocular albinism type 1 and the therapeutic product is tyrosinase (TYR); (157) the eye condition is associated with optic neuritis and the therapeutic product is caspase 2 (CASP2);(158) the eye condition is associated with optic neuritis and the therapeutic product is an anti- Leucine Rich Repeat and Ig Domain Containing Protein 1 (LINGOl) monoclonal antibody; or (159) the eye condition is associated with polypoidal choroidal vasculopathy and the therapeutic product is an anti-complement monoclonal antibody or anti-complement aptamer, wherein the anti-complement monoclonal antibody or aptamer is an anti-complement Cl monoclonal antibody or aptamer, an anti-complement Clq monoclonal antibody / aptamer, an anti-complement Cls monoclonal antibody / aptamer, an anti-complement C2 monoclonal antibody / aptamer, an anti-complement C2a monoclonal antibody or aptamer, an anti-complement C2b monoclonal antibody or aptamer, an anti-complement C3 monoclonal antibody or aptamer, an anti-complement C3a monoclonal antibody or aptamer, an anti-complement C3b monoclonal antibody or aptamer, an anti-complement C4 monoclonal antibody or aptamer, an anti-complement C4a monoclonal antibody or aptamer, an anti-complement C4b monoclonal antibody or aptamer, an anti-complement C5 monoclonal antibody or aptamer, an anti-complement C5a monoclonal antibody or aptamer, an anti-complement C5b monoclonal antibody or aptamer, an anti-complement C6 monoclonal antibody or aptamer, an anti-complement C7 monoclonal antibody or aptamer, an anti-complement C8 monoclonal antibody or aptamer, or an anti-complement C9 monoclonal antibody or aptamer, or preferably an anti-complement C5 antibody.

[0027] In certain embodiments of the methods described herein, the eye condition is associated with X-linked retinitis pigmentosa (XLRP) and the therapeutic product is retinitis pigmentosa GTPase regulator (RPGR). In certain embodiments of any one of the foregoing methods, the eye condition is associated with achromatopsia (ACHM) and the therapeutic product is cyclic nucleotide gated channel beta 3 (CNGB3). In certain embodiments of any one of the foregoing methods, the eye condition is associated with achromatopsia (e.g., CNGA3-linked achromatopsia) and the therapeutic product is cyclic nucleotide gated channel alpha 3 (CNGA3). In certain embodiments of any one of the foregoing methods, the eye condition is associated with retinal dystrophy associated with bi-allelic RPE65 mutations and the therapeutic product is retinoid isomerohydrolase RPE65 (RPE65).

[0028] In certain embodiments of the methods described herein, the eye condition is associated with: (1) Batten-CLN1, and the therapeutic product is palmitoyl-protein thioesterase 1 (PPT1); (2) Batten-CLN2, and the therapeutic product is tripeptidyl- peptidase 1 (TPP1); (3) Batten-CLN3, and the therapeutic product is Battenin (CLN3); (4) uveitis, and the therapeutic product is an anti- interleukin 6 (IL6) monoclonal antibody; (5) uveitis, and the therapeutic product is an anti-TNF-alpha (TNF) monoclonal antibody; (6) diabetic macular edema (DME), and the therapeutic product is an anti-IL6 monoclonal antibody; (7) red-green color blindness, and the therapeutic product is L opsin (OPN1LW); (8) red-green color blindness, and the therapeutic product is M opsin (OPN1MW); (9) blue cone monochromacy, and the therapeutic product is M opsin (OPN1MW); (10) Leber congenital amaurosis 1 (LCA 1), and the therapeutic product is retinal guanylate cyclase 2D (GUCY2D); (11) Leber congenital amaurosis 2 (LCA2), and the therapeutic product is retinal isomerohydrolase RPE65 (RPE65); (12) Leber congenital amaurosis 7 (LCA 7), and the therapeutic product is cone-rod homeobox (CRX); (13) Leber congenital amaurosis 11 (LCA 11), and the therapeutic product is inosine monophosphate dehydrogenase 1 (IMPDH1); (14) Leber congenital amaurosis 12 (LCA 12), and the therapeutic product is retinal degeneration 3, GUCY2D regulator (RD3); (15) Leber congenital amaurosis 13 (LCA 13), and the therapeutic product is retinol dehydrogenase 12 (RDH12); (16) Leber congenital amaurosis 15 (LCA 15), and the therapeutic product is tubby-like protein 1 (TULP1); (17) Leber congenital amaurosis 16 (LCA 16), and the therapeutic product is potassium voltage-gated channel subfamily J member 13 (KCNJ13); (18) Leber hereditary optic neuropathy (LHON), and the therapeutic product is mitochondrially encoded NADH dehydrogenase 1 (MT-ND1); (19) LHON, and the therapeutic product is mitochondrially encoded NADH dehydrogenase 4 (MT-ND4); (20) LHON, and the therapeutic product is mitochondrially encoded NADH dehydrogenase 6 (MT-ND6);(21) Neuromyelitis Optica (NMO), and the therapeutic product is an anti-complement monoclonal antibody or an anti-complement aptamer, wherein the anti-complement monoclonal antibody or aptamer is an anti-complement Cl monoclonal antibody or aptamer, an anti-complement Clq monoclonal antibody or aptamer, an anti-complement Cls monoclonal antibody or aptamer, an anti-complement C2 monoclonal antibody or aptamer, an anti-complement C2a monoclonal antibody or aptamer, an anti-complement C2b monoclonal antibody or aptamer, an anti-complement C3 monoclonal antibody or aptamer, an anti-complement C3a monoclonal antibody or aptamer, an anti-complement C3b monoclonal antibody or aptamer, an anti-complement C4 monoclonal antibody or aptamer, an anti-complement C4a monoclonal antibody or aptamer, an anti-complement C4b monoclonal antibody or aptamer, an anti-complement C5 monoclonal antibody or aptamer, an anti-complement C5a monoclonal antibody or aptamer, an anti-complement C5b monoclonal antibody or aptamer, an anti-complement C6 monoclonal antibody or aptamer, an anti-complement C7 monoclonal antibody or aptamer, an anti-complement C8 monoclonal antibody or aptamer, or an anti-complement C9 monoclonal antibody or aptamer, or preferably an anti-complement C5 antibody; (22) NMO, and the therapeutic product is an anti-IL6 monoclonal antibody; (23) Uveitis, and the therapeutic product is an anti-complement C5 monoclonal antibody; (24) Uveitis, and the therapeutic product is angiotensin I converting enzyme (ACE); (25) Uveitis, and the therapeutic product is interleukin 10 (IL10); (26) Uveitis, and the therapeutic product is an anti-TNF monoclonal antibody; (27) X-linked retinoschisis (XLRS), and the therapeutic product is retinoschisin (RS1); (28) Bardet-Biedl Syndrome 1, and the therapeutic product is Bardet-Biedl Syndrome 1 (BBS1); (29) Bardet-Biedl Syndrome 3, and the therapeutic product is ADP ribosylation factor-like GTPase 6 (ARL6); (30) Bardet-Biedl Syndrome 5, and the therapeutic product is Bardet-Biedl Syndrome 5 (BBS5); (31) Bardet-Biedl Syndrome 6, and the therapeutic product is McKusick-Kaufman Syndrome (MKKS); (32) Bardet-Biedl Syndrome 10, and the therapeutic product is Bardet-Biedl Syndrome 10 (BBS10); (33) Bardet-Biedl Syndrome 11, and the therapeutic product is Tripartite motif containing 32 (TRIM32); (34) Bardet-Biedl Syndrome 13, and the therapeutic product is MKS transition zone complex subunit 1 (MKS1); (35) Bardet-Biedl Syndrome 18, and the therapeutic product is BBSome interacting protein 1 (BBIP1); (36) Bardet-Biedl Syndrome 19, and the therapeutic product is Intraflagellar transport 27 (IFT27); (37) Cone Dystrophy, and the therapeutic product is Guanylate cyclase activator 1A (GUCA1A); (38) Retinitis Pigmentosa 13, and the therapeutic product is Pre-mRNA processing factor 8 (PRPF8);(39) retinitis pigmentosa 37, and the therapeutic product is nuclear receptor subfamily 2, group E, member 3 (NR2E3); or (40) Best disease, and the therapeutic product is bestrophin 1 (BEST1).

[0029] In certain embodiments of the methods described herein, the eye condition is associated with a retinal dystrophy associated with a bi-allelic RPE65 mutation, and the therapeutic product is retinal isomerohydrolase RPE65 (RPE65).

[0030] In certain embodiments of the methods described herein, the eye condition is associated with: (1) Batten-CLN2, and the therapeutic product is tripeptidyl- peptidase 1 (TPP1); (2) Usher Syndrome Type 1, and the therapeutic product is myosin VIIA (MY07A); (3) Usher Syndrome Type 1, and the therapeutic product is cadherin-related 23 (CDH23); (4) Usher Syndrome Type 2, and the therapeutic product is protocadherin-related 15 (PCDH15); (5) Usher Syndrome Type 2, and the therapeutic product is Usherin (USH2A); (6) Usher Syndrome Type 3, and the therapeutic product is Clarin 1 (CLRN1); (7) Stargardt Disease, and the therapeutic product is ATP-binding cassette subfamily A member 4 (ABCA4); (8) Stargardt Disease, and the therapeutic product is ELOVL fatty acid elongase 4 (ELOVL4); (9) Red-Green Color Blindness, and the therapeutic product is L opsin (OPN1LW); (10) Red-Green Color Blindness, and the therapeutic product is M opsin (OPN1MW); (11) Blue Cone Monochromacy, and the therapeutic product is M opsin (OPN1MW); (12) Leber Congenital Amaurosis 1 (LCA 1), and the therapeutic product is retinal guanylate cyclase 2D (GUCY2D); (13) Leber Congenital Amaurosis 2 (LCA 2), and the therapeutic product is retinoid isomerohydrolase RPE65 (RPE65); (14) Leber Congenital Amaurosis 4 (LCA 4), and the therapeutic product is aryl hydrocarbon receptor interacting protein-like 1 (AIPL1); (15) Leber Congenital Amaurosis 7 (LCA 7), and the therapeutic product is cone-rod homeobox (CRX); (16) Leber Congenital Amaurosis 8 (LCA 8), and the therapeutic product is Crumbs cell polarity complex component 1 (CRB1); (17) Leber Congenital Amaurosis 9 (LCA 9), and the therapeutic product is nicotinamide nucleotide adenylyltransferase 1 (NMNAT1); (18) Leber Congenital Amaurosis 10 (LCA 10), and the therapeutic product is centrosomal protein 290 (CEP290); (19) Leber Congenital Amaurosis 11 (LCA 11), and the therapeutic product is inosine monophosphate dehydrogenase 1 (IMPDH1); (20) Leber Congenital Amaurosis 15 (LCA 15), and the therapeutic product is tubby-like protein 1 (TULP1); (21) LHON, and the therapeutic product is mitochondrially-encoded NADH dehydrogenase 4 (MT-ND4); (22) LHON, and the therapeutic product is mitochondrially-encoded NADH dehydrogenase 6 (MT-ND6); (23) Choroideremia, and the therapeutic product is Rab escort protein 1 (CHM); (24) X-linked Retinoschisis (XLRS), and the therapeutic product is retinoschisin (RS1);(25) Bardet-Biedl Syndrome 1, and the therapeutic product is Bardet-Biedl Syndrome 1 (BBS1); (26) Bardet-Biedl Syndrome 6, and the therapeutic product is McKusick-Kaufman Syndrome (MKKS); (27) Bardet-Biedl Syndrome 10, and the therapeutic product is Bardet-Biedl Syndrome 10 (BBS10); (28) Cone Dystrophy, and the therapeutic product is Guanylate Cyclase Activator 1A (GUCA1A); (29) Optic Atrophy, and the therapeutic product is OPA1 Mitochondrial Motor Protein-Like GTPase (OPA1); (30) Retinitis Pigmentosa 1, and the therapeutic product is RP1 Axon Microtubule- Associated (RP1); (31) Retinitis Pigmentosa 2, and the therapeutic product is RP2 Activator of ARL3 GTPase (RP2); (32) Retinitis Pigmentosa 7, and the therapeutic product is Peripherin 2 (PRPH2); (33) Retinitis Pigmentosa 11, and the therapeutic product is Pre-mRNA Processing Factor 31 (PRPF31); (34) Retinitis Pigmentosa 13, and the therapeutic product is Pre-mRNA Processing Factor 8 (PRPF8); (35) Retinitis Pigmentosa 37, and the therapeutic product is Nuclear Receptor Subfamily 2, Group E, Member 3 (NR2E3); (36) Retinitis Pigmentosa 38, and the therapeutic product is MER Proto-Oncogene Tyrosine Kinase (MERTK); (37) Retinitis Pigmentosa 40, and the therapeutic product is Phosphodiesterase 6B (PDE6B); (38) Retinitis Pigmentosa 41, and the therapeutic product is Prominin 1 (PROM1); (39) Retinitis Pigmentosa 56, and the therapeutic product is Interphotoreceptor Matrix Proteoglycan 2 (IMPG2); (40) Retinitis Pigmentosa 62, and the therapeutic product is Male Germ Cell Associated Kinase (MAK); (41) Retinitis Pigmentosa 80, and the therapeutic product is Intraflagellar Transport Protein 140 (IFT140); or (42) Best Disease, and the therapeutic product is Bestrophin 1 (BEST1).

[0031] In certain embodiments of the methods described herein, the ocular condition is associated with X-linked retinitis pigmentosa (XLRP), and the therapeutic product is retinitis pigmentosa GTPase regulator (RPGR). In certain embodiments of any of the foregoing methods, the ocular condition is associated with achromatopsia, and the therapeutic product is cyclic nucleotide-gated channel beta 3 (CNGB3); or achromatopsia (e.g., CNGA3-linked achromatopsia), and the therapeutic product is cyclic nucleotide-gated channel alpha 3 (CNGA3).

[0032] In certain embodiments of the methods described herein, the recombinant viral vector further comprises a nucleotide sequence encoding a promoter or enhancer-promoter operably linked to the nucleotide sequence encoding the therapeutic product, and wherein the promoter or enhancer-promoter is a ubiquitous promoter / enhancer-promoter, an eye-specific promoter / enhancer-promoter, or a retina-specific promoter / enhancer-promoter.

[0033] In certain embodiments of the methods described herein, the recombinant viral vector further comprises a nucleotide sequence encoding a promoter or enhancer-promoter operably linked to the nucleotide sequence encoding the therapeutic product, and wherein the promoter or enhancer-promoter is: (1) a CAG promoter; (2) a CBA promoter; (3) a CMV promoter; (4) a 1.7 kb red cone opsin promoter (PR1.7 promoter); (5) a rhodopsin kinase (GRK1) photoreceptor-specific enhancer-promoter (see, e.g., Young et al., 2003, Retinal Cell Biology; 44:4076-4085); (6) a hCARp promoter, which is a human cone arrestin promoter; (7) a hRKp, which is a rhodopsin kinase promoter; (8) a cone photoreceptor-specific human arrestin 3 (ARR3) promoter; (9) a rhodopsin promoter; or (10) a U6 promoter (especially when the therapeutic product is a small RNA such as an shRNA and an siRNA).

[0034] In certain embodiments of the methods described herein, the recombinant viral vector further comprises a nucleotide sequence encoding a cone-specific promoter operably linked to the nucleotide sequence encoding the therapeutic product, and wherein: (1) the eye condition is associated with red-green color blindness and the therapeutic product is L opsin (OPN1LW); (2) the eye condition is associated with red-green color blindness and the therapeutic product is M opsin (OPN1MW); (3) the eye condition is associated with blue cone monochromacy and the therapeutic product is M opsin (OPN1MW); (4) the eye condition is associated with cone dystrophy and the therapeutic product is Guanylate cyclase activator 1A (GUCA1A); or (5) the eye condition is associated with blue cone monochromacy (BCM) and the therapeutic product is L opsin (OPN1LW).

[0035] In certain embodiments of the methods described herein, the administering step delivers a therapeutically effective amount of the therapeutic product to the retina of the human subject.

[0036] In certain embodiments of the methods described herein, the therapeutically effective amount of the therapeutic product is produced by human retinal cells of the human subject.

[0037] In certain embodiments of the methods described herein, the therapeutically effective amount of the therapeutic product is produced by human photoreceptor cells, horizontal cells, bipolar cells, amacrine cells, retinal ganglion cells, and / or retinal pigment epithelial cells in the outer limiting membrane of the human subject.

[0038] In certain embodiments of the methods described herein, the human photoreceptor cells are cone cells and / or rod cells.

[0039] In certain embodiments of the methods described herein, the retinal ganglion cells are dwarf cells, umbrella cells, biiayer cells, giant retinal ganglion cells, photosensitive ganglion cells, and / or Miiller glia.

[0040] In certain embodiments of the methods described herein, the recombinant viral vector is a rAAV vector (e.g., a rAAV8, rAAV2, rAAV2tYF, or rAAV5 vector).

[0041] In certain embodiments of the methods described herein, wherein the recombinant viral vector is a rAAV8 vector.

[0042] In certain embodiments of the methods described herein, the methods further comprise a step of monitoring the temperature of the surface of the eye using an infrared thermal imager after the administering step. In a particular embodiment, the infrared thermal imager is a FLIR T530 infrared thermal imager. In a particular embodiment, the infrared thermal imager is a FLIR T420 infrared thermal imager. In a particular embodiment, the infrared thermal imager is a FLIR T440 infrared thermal imager. In a particular embodiment, the infrared thermal imager is a Fluke Ti400 infrared thermal imager. In a particular embodiment, the infrared thermal imager is a FLIRE60 infrared thermal imager. In a particular embodiment, the infrared resolution of the infrared thermal imager is equal to or greater than 75,000 pixels. In a particular embodiment, the thermal sensitivity of the infrared thermal imager is equal to or less than 0.05°C at 30°C. In a particular embodiment, the field of view (FOV) of the infrared thermal imager is equal to or lower than 25° x 25°.

[0043] In certain embodiments of the methods described herein, the delivering to the eye comprises delivering to the retina, choroid, and / or vitreous humor of the eye.

[0044] In certain embodiments, the recombinant vector used to deliver the therapeutic product should be tropic to cells of the eye, such as human retinal cells (e.g., photoreceptor cells). Such vectors can include non-replicating recombinant adeno-associated viral vectors (“rAAV”), with those bearing an AAV8 capsid being preferred. However, other recombinant viral vectors can be used, including but not limited to recombinant lentiviral vectors, vaccinia virus vectors, or non-viral expression vectors known as “naked DNA” constructs. Preferably, expression of the therapeutic product should be controlled by appropriate expression control elements, such as (1) a CAG promoter; (2) a CBA promoter; (3) a CMV promoter; (4) a PR1.7 promoter; (5) a rhodopsin kinase (GRK1) photoreceptor-specific enhancer-promoter; (6) a hCARp promoter; (7) a hRKp; (8) a cone photoreceptor-specific human arrestin 3 (ARR3) promoter; (9) a rhodopsin promoter; or (10) a U6 promoter, and can include other expression control elements that enhance expression of the therapeutic product driven by the vector (e.g., introns, such as a chicken beta-actin intron, a mouse minute virus (MVM) intron, a human factor IX intron (e.g., FIX truncated intron 1), a beta-globin splice donor / immunoglobulin heavy chain splice acceptor intron, an adenovirus splice donor / immunoglobulin splice acceptor intron, an SV40 late splice donor / acceptor (19S / 16S) intron, and a hybrid adenovirus splice donor / IgG splice acceptor intron, and polyA signals, such as a rabbit beta-globin polyA signal, a human growth hormone (hGH) polyA signal, an SV40 late polyA signal, a synthetic polyA (SPA) signal, and a bovine growth hormone (bGH) polyA signal). See, e.g., Powell and Rivera-Soto, 2015, Discov. Med., 19(102):49-57.

[0045] In certain embodiments of the methods described herein, a therapeutically effective dose of the recombinant vector is administered (1) to the subretinal space without vitrectomy (e.g., via the suprachoroidal space or via peripheral injection), (2) to the suprachoroidal space, (3) to the episcleral space (i.e., a paraskeral administration), (4) to the subretinal space via vitrectomy, or (5) to the vitreous cavity, in a volume ranging from 50-100 μΐ or 100-500 μΐ, preferably 100-300 μΐ and most preferably 250 μΐ, depending on the method of administration. In certain embodiments, a therapeutically effective dose of the recombinant vector is administered suprachoroidally in a volume of 100 μΐ or less, e.g., in a volume of 50-100 μΐ. In certain embodiments, a therapeutically effective dose of the recombinant vector is administered to the outer surface of the sclera (e.g., by a posterior paraskeral depot procedure) in a volume of 500 μΐ or less, e.g., in a volume of 10-20 μΐ, 20-50 μΐ, 50-100 μΐ, 100-200 μΐ, 200-300 μΐ, 300-400 μΐ, or 400-500 μΐ. In certain embodiments, a therapeutically effective dose of the recombinant vector is administered to the subretinal space via peripheral injection in a volume ranging from 50-100 μΐ or 100-500 μΐ, preferably 100-300 μΐ and most preferably 250 μΐ.

[0046] In certain embodiments, optokinetic nystagmus (OKN) is assessed to measure the vision of a patient. In certain embodiments, OKN can be used, e.g., Cetinkaya et al., 2008, Eye, 22:77-81; Hyon et al., 2010, IOVS, 51(2): 752-757; Han et al., 2011, IOVS, 52(10): 7492-7497; Wester et al., 2007, IOVS, 48(10):4542-4548; Palmowski-Wolfe et al., 2019, J. AAPOS, 23(4): e49; Turuwhenua et al., Objective Assessment of Visual Performance Using Optokinetic Nystagmus in Young Children, October 2016, <https: / / www.researchgate.net / publication / 303593 1 10_Objective_Assessment_of_Visual_Performance_Using_Optokinetic_Nystagmus_in_Young_Children> (last accessed 10 / 30 / 2020). anzctr.org.au / AnzctrAttachments / 371914-OKN% 20protocol.pdf Figure 1and the methods and / or devices described and disclosed in Objective Acuity and Aier Eye Hospital Group Announce Strategic Cooperation Agreement, Cision PR Newswire, July 25, 2019, retrieved from the World Wide Web at <prnewswire.com / news-releases / objective-acuity-and-aier-eye-hospital-group-announce-a-strategic-cooperation-agreement-300891165.html>, each of which is incorporated herein by reference in its entirety.

[0047] Without being bound by theory, this vision screening uses the principles of OKN in voluntary reflex to objectively assess whether a patient’s eyes can follow a moving target. By using OKN, there is no need for verbal communication between the tester and the patient. Thus, OKN can be used to measure the vision of preverbal and / or nonverbal patients. In certain embodiments, OKN is used to measure the vision of a patient who is 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 1 year, 1.5 years, 2 years, 2.5 years, 3 years, 3.5 years, 4 years, 4.5 years, or 5 years old. In certain embodiments, the iPad is used to measure vision via detection of OKN reflexes when the patient is watching motion on the iPad.

[0048] Without being bound by theory, this vision screening uses the principle of OKN involuntary reflex to objectively assess whether a patient's eyes can follow a moving target. By using OKN, there is no need for verbal communication between the tester and the patient. Thus, OKN can be used to measure the vision of preverbal and / or nonverbal patients. In certain embodiments, OKN is used to measure the vision of patients less than 1.5 months, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 1 year, 1.5 years, 2 years, 2.5 years, 3 years, 3.5 years, 4 years, 4.5 years, or 5 years old. In another particular embodiment, OKN is used to measure the vision of patients 1-2 months, 2-3 months, 3-4 months, 4-5 months, 5-6 months, 6-7 months, 7-8 months, 8-9 months, 9-10 months, 10-11 months, 11 months to 1 year, 1-1.5 years, 1.5-2 years, 2-2.5 years, 2.5-3 years, 3-3.5 years, 3.5-4 years, 4-4.5 years, or 4.5-5 years old. In another particular embodiment, OKN is used to measure the vision of patients 6 months to 5 years old. In certain embodiments, vision is measured via detection of OKN reflex using an iPad when the patient is watching movement on the iPad.

[0049] In certain embodiments, in patients exhibiting Batten-CLN2 related vision loss, vision is assessed by measuring OKN prior to treating the patient with an AAV, preferably AAV8 or AAV9, encoding tripeptidyl-peptidase 1 (TPP1). In particular, patients exhibiting Batten-CLN2 related vision loss are in the age and / or age range described above. In certain embodiments, in patients exhibiting Batten-CLN2 related vision loss up to 5 years old, vision is assessed by measuring OKN after treating the patient with an AAV, preferably AAV8 or AAV9, encoding tripeptidyl-peptidase 1. In certain embodiments, OKN based vision assessment determines that vision is not reduced after treatment with the AAV gene therapy. In certain embodiments, OKN based vision assessment determines that vision of the patient is improved by 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% after treatment with the AAV gene therapy. In certain embodiments, OKN based vision assessment determines that vision of the patient is not further deteriorated after treatment with the AAV gene therapy.

[0050] In certain embodiments, in a patient exhibiting Batten-CLN2-associated vision loss, vision is assessed by measuring OKN prior to treating the patient with an AAV, preferably AAV8 or AAV9, encoding TPP1. Specifically, the patient exhibiting Batten-CLN2-associated vision loss is up to 5 years of age and / or within the age range described above. In certain embodiments, in a patient exhibiting Batten-CLN2-associated vision loss, vision is assessed by measuring OKN after treating the patient with an AAV, preferably AAV8 or AAV9, encoding tripeptidyl-peptidase 1. In certain embodiments, OKN-based vision assessment determines that vision is not decreased after treatment with AAV gene therapy. In certain embodiments, OKN-based vision assessment determines that the patient’s vision is improved by at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or at least 100% after treatment with AAV gene therapy. In certain embodiments, OKN-based vision assessment determines that the patient’s vision is not further deteriorated after treatment with AAV gene therapy.

[0051] In certain embodiments, in a patient exhibiting Batten-CLN1-associated vision loss, vision is assessed by measuring OKN prior to treating the patient with an AAV, preferably AAV8 or AAV9, encoding palmitoyl-protein thioesterase 1 (PPT1). Specifically, the patient exhibiting Batten-CLN1-associated vision loss is up to 5 years of age and / or within the age range described above. In certain embodiments, in a patient exhibiting Batten-CLN1-associated vision loss, vision is assessed by measuring OKN after treating the patient with an AAV, preferably AAV8 or AAV9, encoding PPT1. In certain embodiments, OKN-based vision assessment determines that vision is not decreased after treatment with AAV gene therapy. In certain embodiments, OKN-based vision assessment determines that the patient’s vision is improved by 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% after treatment with AAV gene therapy. In certain embodiments, OKN-based vision assessment determines that the patient’s vision is not further deteriorated after treatment with AAV gene therapy.

[0052] In certain embodiments, in a patient exhibiting Batten-CLN1 -related vision loss, vision is assessed by measuring OKN prior to treating the patient with an AAV, preferably AAV8 or AAV9, encoding PPT1. Specifically, the patient exhibiting Batten-CLN1 -related vision loss is in the age and / or age range described above. In certain embodiments, in a patient exhibiting Batten-CLN1 -related vision loss up to 5 years of age, vision is assessed by measuring OKN after treating the patient with an AAV, preferably AAV8 or AAV9, encoding PPT1. In certain embodiments, the OKN-based vision assessment determines that vision is not decreased after treatment with the AAV gene therapy. In certain embodiments, the OKN-based vision assessment determines that the patient’s vision is improved by at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or at least 100% after treatment with the AAV gene therapy. In certain embodiments, the OKN-based vision assessment determines that the patient’s vision is not further deteriorated after treatment with the AAV gene therapy.

[0053] In certain embodiments, in a patient exhibiting Batten-CLN3 -related vision loss, vision is assessed by measuring OKN prior to treating the patient with an AAV, preferably AAV8 or AAV9, encoding Battenin (CLN3). Specifically, the patient exhibiting Batten-CLN3 -related vision loss is in the age and / or age range described above. In certain embodiments, in a patient exhibiting Batten-CLN3 -related vision loss up to 5 years of age, vision is assessed by measuring OKN after treating the patient with an AAV, preferably AAV8 or AAV9, encoding Battenin (CLN3). In certain embodiments, the OKN-based vision assessment determines that vision is not decreased after treatment with the AAV gene therapy. In certain embodiments, the OKN-based vision assessment determines that the patient’s vision is improved by 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% after treatment with the AAV gene therapy. In certain embodiments, the OKN-based vision assessment determines that the patient’s vision is not further deteriorated after treatment with the AAV gene therapy.

[0054] In certain embodiments, in a patient exhibiting Batten-CLN3-associated vision loss, vision is assessed by measuring OKN prior to treating the patient with an AAV, preferably AAV8 or AAV9, encoding Battenin (CLN3). Specifically, the patient exhibiting Batten-CLN3-associated vision loss is up to 5 years of age and / or within the age range described above. In certain embodiments, in a patient exhibiting Batten-CLN3-associated vision loss, vision is assessed by measuring OKN after treating the patient with an AAV, preferably AAV8 or AAV9, encoding Battenin (CLN3). In certain embodiments, OKN-based vision assessment determines that vision is not decreased after treatment with AAV gene therapy. In certain embodiments, OKN-based vision assessment determines that the patient’s vision is improved by at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or at least 100% after treatment with AAV gene therapy. In certain embodiments, OKN-based vision assessment determines that the patient’s vision is not further deteriorated after treatment with AAV gene therapy.

[0055] In certain embodiments, in a patient exhibiting Batten-CLN6-associated vision loss, vision is assessed by measuring OKN prior to treating the patient with an AAV, preferably AAV8 or AAV9, encoding CLN6 transmembrane ER protein (CLN6). Specifically, the patient exhibiting Batten-CLN6-associated vision loss is up to 5 years of age and / or within the age range described above. In certain embodiments, in a patient exhibiting Batten-CLN6-associated vision loss, vision is assessed by measuring OKN after treating the patient with an AAV, preferably AAV8 or AAV9, encoding CLN6 transmembrane ER protein (CLN6). In certain embodiments, OKN-based vision assessment determines that vision is not decreased after treatment with AAV gene therapy. In certain embodiments, OKN-based vision assessment determines that the patient’s vision is improved by 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% after treatment with AAV gene therapy. In certain embodiments, OKN-based vision assessment determines that the patient’s vision is not further deteriorated after treatment with AAV gene therapy.

[0056] In certain embodiments, in a patient exhibiting Batten-CLN6-associated vision loss, vision is assessed by measuring OKN prior to treating the patient with an AAV, preferably AAV8 or AAV9, encoding CLN6 transmembrane ER protein (CLN6). Specifically, the patient exhibiting Batten-CLN6-associated vision loss is up to 5 years of age and / or within the age range described above. In certain embodiments, in a patient exhibiting Batten-CLN6-associated vision loss, vision is assessed by measuring OKN after treating the patient with an AAV, preferably AAV8 or AAV9, encoding CLN6 transmembrane ER protein (CLN6). In certain embodiments, OKN-based vision assessment determines that vision is not decreased after treatment with AAV gene therapy. In certain embodiments, OKN-based vision assessment determines that the patient’s vision is improved by at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or at least 100% after treatment with AAV gene therapy. In certain embodiments, OKN-based vision assessment determines that the patient’s vision is not further deteriorated after treatment with AAV gene therapy.

[0057] In certain embodiments, in a patient exhibiting Batten-CLN7-associated vision loss, vision is assessed by measuring OKN prior to treating the patient with an AAV, preferably AAV8 or AAV9, encoding MFSD8. Specifically, the patient exhibiting Batten-CLN7-associated vision loss is up to 5 years of age and / or within the age range described above. In certain embodiments, in a patient exhibiting Batten-CLN7-associated vision loss, vision is assessed by measuring OKN after treating the patient with an AAV, preferably AAV8 or AAV9, encoding MFSD8. In certain embodiments, OKN-based vision assessment determines that vision is not decreased after treatment with AAV gene therapy. In certain embodiments, OKN-based vision assessment determines that the patient’s vision is improved by 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% after treatment with AAV gene therapy. In certain embodiments, OKN-based vision assessment determines that the patient’s vision is not further deteriorated after treatment with AAV gene therapy.

[0058] In certain embodiments, in patients exhibiting Batten-CLN7-associated vision loss, vision is assessed by measuring OKN prior to treating the patient with an AAV, preferably AAV8 or AAV9, encoding MFSD8. Specifically, patients exhibiting Batten-CLN7-associated vision loss are in the age and / or age range described above. In certain embodiments, in patients exhibiting Batten-CLN7-associated vision loss up to 5 years of age, vision is assessed by measuring OKN after treating the patient with an AAV, preferably AAV8 or AAV9, encoding MFSD8. In certain embodiments, the OKN-based vision assessment determines that vision is not decreased after treatment with the AAV gene therapy. In certain embodiments, the OKN-based vision assessment determines that the patient’s vision is improved by at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or at least 100% after treatment with the AAV gene therapy. In certain embodiments, the OKN-based vision assessment determines that the patient’s vision is not further deteriorated after treatment with the AAV gene therapy.

[0059] Subretinal administration via vitrectomy is a surgical procedure performed by a trained retinal physician that involves performing a vitrectomy on a subject under local anesthesia and injecting a gene therapy subretinally into the retina (see, e.g., Campochiaro et al., 2017, Hum Gen Ther 28(1):99-111, which is incorporated by reference herein in its entirety). Alternatively, subretinal administration can be performed without the need for vitrectomy. In one particular embodiment, subretinal administration without the need for vitrectomy is via the suprachoroidal space using a suprachoroidal catheter that injects a drug into the subretinal space, such as a subretinal drug delivery device comprising a catheter that can be inserted through the suprachoroidal space and towards the posterior pole, a small needle is injected into the subretinal space at the posterior pole (see, e.g., Baldassarre et al., 2017, Subretinal Delivery of Cells via the Suprachoroidal Space: Janssen Trial. In Schwartz et al. (eds) Cellular Therapies for Retinal Disease, Springer, Cham; International Patent Application Publication No. WO 2016 / 040635 Al; each of which is incorporated by reference herein in its entirety). In another particular embodiment, subretinal administration without the need for vitrectomy is via peripheral injection. In other words, the recombinant vector can be delivered to the subretinal space by peripheral injection into the retina (i.e., the optic disc, fovea, and macula periphery located in the back of the eye) without the need for performing a vitrectomy. This can be accomplished by a transvitreal injection. The suprachoroidal administration procedure involves administering a drug to the suprachoroidal space of an eye, and is typically performed using a suprachoroidal drug delivery device, such as a microinjector with a microneedle (see, e.g., Hariprasad, 2016, Retinal Physician 13:20-23; Goldstein, 2014, Retina Today 9(5):82-87; each of which is incorporated by reference herein in its entirety).

[0060] According to the present application described herein, suprachoroidal drug delivery devices that can be used to deposit a recombinant vector in the suprachoroidal space include, but are not limited to, the Clearside Biotech® Suprachoroidal Drug Delivery Device (Clearside Biotech, Inc., Atlanta, GA) and the OcuSys® Suprachoroidal Drug Delivery Device (OcuSys, Inc., Atlanta, GA). ®The choroidal drug delivery device manufactured by Biomedical, Inc. (see, for example, Hariprasad, 2016, Retinal Physician 13: 20-23) and the MedOne choroidal catheter. According to the invention described herein, subretinal drug delivery devices for depositing recombinant carriers into the subretinal space via the suprachoroidal space include, but are not limited to, subretinal drug delivery devices manufactured by Janssen Pharmaceuticals, Inc. (see, for example, International Patent Application Publication No. WO 2016 / 040635 A1). According to the invention described herein, subretinal drug delivery devices for depositing recombinant carriers into the subretinal space via peripheral injection methods include, but are not limited to, a sharp needle that can be inserted into the sclera via the upper or lower side of the eye (e.g., at the 2 o'clock or 10 o'clock position) and completely through the vitreous body for injection into the retina of the other side, and a cannula needle that can be inserted into the sclera to allow insertion of a subretinal cannula into the eye and through the vitreous body to reach the desired injection area. In one particular implementation, application to the outer surface of the sclera is performed via a parascleral drug delivery device comprising a cannula, the tip of which can be inserted into and held directly juxtaposed with the scleral surface.

[0061] Application via suprachoroidal, subretinal, parascleral, intravitreal, subconjunctival, and / or intraretinal administration should result in delivery of the soluble therapeutic product to the retina, vitreous fluid, and / or aqueous solution. Expression of the therapeutic product by retinal cells, such as rod cells, cone cells, retinal pigment epithelial cells, horizontal cells, bipolar cells, amacrine cells, ganglion cells, and / or Miller cells, results in delivery and maintenance of the therapeutic product in the retina, vitreous fluid, and / or aqueous solution. In certain embodiments, because the therapeutic product is continuously produced, maintaining a low concentration may be effective. The concentration of the therapeutic product can be measured in patient samples of vitreous fluid and / or aqueous solution from the anterior chamber of the treated eye. Alternatively, the vitreous fluid concentration can be estimated and / or monitored by measuring the serum concentration of the therapeutic product in the patient—the ratio of systemic to vitreous exposure to the therapeutic product is approximately 1:90,000. (See, for example, Table 5 of Xu L et al., 2013, Invest. Opthal. Vis. Sci. 54:1616-1624, pp. 1621 and 1623, for vitreous fluid and serum concentrations of ranibizumab, which are incorporated herein by reference in their entirety.)

[0062] Pharmaceutical compositions suitable for administration to the choroid, subretinal, parascleral, intravitreal, subconjunctival, and / or intraretinal regions comprise a suspension of the recombinant carrier in a formulation buffer comprising a physiologically compatible aqueous buffer, a surfactant, and optionally an excipient.

[0063] The present application has several advantages over standard of care treatment involving repeated ocular injections of boluses of high doses of therapeutic products that dissipate over time leading to highest and lowest levels. In contrast to repeated injections of therapeutic products, the sustained expression of therapeutic products leads to a more consistent level of antibody present at the site of action, is less risky and is more convenient for the patient as the number of injections that need to be performed is less, leading to a reduction in physician visits. The consistent protein production can lead to better clinical outcomes as rebound of retinal edema is less likely. Furthermore, in certain embodiments, the therapeutic product expressed from the recombinant vector is post-translationally modified in a different way than the therapeutic product injected directly, due to the different microenvironment present during and after translation. Without being bound by any particular theory, this leads to a therapeutic product with different diffusion, bioactivity, distribution, affinity, pharmacokinetic and immunogenicity characteristics, thus the therapeutic product delivered to the site of action is a "biobetter" compared to the therapeutic product injected directly.

[0064] Additionally, when the therapeutic product is an antibody, the antibody expressed in vivo from the recombinant vector is less likely to contain degradation products associated with recombinantly produced antibodies, such as protein aggregation and protein oxidation. Aggregation is a problem associated with protein production and storage due to high protein concentrations, interaction with surfaces of manufacturing equipment and containers, and purification with certain buffer systems. These conditions that promote aggregation are not present in antibody expression for gene therapy. Oxidation, such as methionine, tryptophan, and histidine oxidation, is also associated with protein production and storage and is caused by stressed cell culture conditions, metal and air contact, and impurities in buffers and excipients. Proteins expressed in vivo from the recombinant vector can also be oxidized in stressed conditions. However, humans and many other organisms are equipped with antioxidant defense systems that not only reduce oxidative stress, but sometimes also repair and / or reverse oxidation. Thus, proteins produced in vivo are less likely to be in an oxidized form. Both aggregation and oxidation can affect potency, pharmacokinetics (clearance), and immunogenicity.

[0065] Unlike small molecule drugs, biologies often comprise a mixture of many variants with different modifications or forms that have different potencies, pharmacokinetics, and safety profiles. For a therapeutic product that is post-translationally modified after expression in cells of the eye, not every molecule produced in gene therapy or protein therapy needs to be post-translationally modified completely. Rather, the population of such therapeutic products produced should have sufficient post-translational modification (e.g., about 1% to about 10% of the population, about 1% to about 20% of the population, about 1% to about 50% of the population, or about 10% to about 50% of the population) to demonstrate efficacy. The goal of the gene therapy treatments provided herein is to slow down or stop the progression of the eye condition with minimal intervention / invasive surgery and to slow down or prevent vision loss. Efficacy can be monitored by measuring BCVA (best corrected visual acuity), intraocular pressure, slit lamp biopsy, indirect ophthalmoscopy, SD-OCT (SD-optical coherence tomography), electroretinography (ERG). Signs of vision loss, infection, inflammation, and other safety events (including retinal detachment) can also be monitored. In certain embodiments, retinal thickness can be monitored to determine efficacy of the treatments provided herein. Without being bound by any particular theory, in particular embodiments, retinal thickness can be used as a clinical readout, where the greater the reduction in retinal thickness or the longer the time before the retinal thickens, the more effective the treatment. Retinal thickness can be determined, for example, by SD-OCT. SD-OCT is a three-dimensional imaging technique that uses low-coherence interferometry to determine the magnitude of the backscattered light reflected from a target object. OCT can be used to scan the layers of a tissue sample (e.g., the retina) with 3-15 μm axial resolution, and SD-OCT improves axial resolution and scanning speed compared to previous versions of the technology (Schuman, 2008, Trans. Am. Opthamol. Soc. 106:426-458). Retinal function can be determined, for example, by ERG. ERG is a non-invasive electrophysiological test of retinal function in humans that is FDA-approved for use in humans, which examines the photoreceptor cells (rods and cones) of the eye and their connected ganglion cells, particularly their response to a flash of light.

[0066] 4.1 Illustrative Embodiments

[0067] 4.1.1 Group 1

[0068] 1. A method of subretinal administration for treating an eye condition without the need for vitrectomy, comprising administering to the subretinal space in the eye of a human subject in need of treatment a recombinant viral vector comprising a nucleotide sequence encoding a therapeutic product, such that the therapeutic product is expressed and the eye condition is treated, wherein the method does not comprise performing a vitrectomy on the eye of the human patient.

[0069] 2. The method of paragraph 1, wherein the administering step comprises administering the recombinant viral vector therapeutic product to the subretinal space of the eye of the human subject via the suprachoroidal space of the eye of the human subject.

[0070] 3. The method of paragraph 2, wherein the administering step is by use of a subretinal drug delivery device comprising a catheter that can be inserted through the suprachoroidal space and towards the posterior pole for injection into the subretinal space at the posterior pole with a small needle.

[0071] 4. The method of paragraph 3, wherein the administering step comprises inserting the catheter of the subretinal drug delivery device through the suprachoroidal space.

[0072] 5. A method for suprachoroidal administration for treating an ocular condition, comprising administering to the suprachoroidal space of the eye of a human subject in need of treatment a recombinant viral vector comprising a nucleotide sequence encoding a therapeutic product, such that the therapeutic product is expressed and the ocular condition is treated.

[0073] 6. The method of paragraph 5, wherein the administering step is by injection of the recombinant viral vector into the suprachoroidal space using a suprachoroidal drug delivery device.

[0074] 7. The method of paragraph 5 or 6, wherein the suprachoroidal drug delivery device is a microinjector.

[0075] 8. A method for juxtasceral administration for treating an ocular condition, comprising administering to the juxtasceral space of the eye of a human subject in need of treatment a recombinant viral vector comprising a nucleotide sequence encoding a therapeutic product, such that the therapeutic product is expressed and the ocular condition is treated.

[0076] 9. The method of paragraph 8, wherein the administering step is by use of a juxtasceral drug delivery device comprising a cannula whose tip can be inserted and held in direct apposition to the surface of the sclera.

[0077] 10. The method of paragraph 9, wherein the administering step comprises inserting the tip of the cannula and holding it in direct apposition to the surface of the sclera.

[0078] 11. The method of any one of paragraphs 1-10, wherein the therapeutic product is not an anti-human vascular endothelial growth factor (hVEGF) antibody.

[0079] 12. The method of any one of paragraphs 1-11, wherein the ocular condition is not associated with neovascular age-related macular degeneration (nAMD).

[0080] 13. A method of subretinal administration for treating an ocular condition concomitant with vitrectomy, comprising administering to the subretinal space in the eye of a human subject in need of treatment a recombinant viral vector comprising a nucleotide sequence encoding a therapeutic product, such that the therapeutic product is expressed and the ocular condition is treated, wherein the method comprises performing a vitrectomy on the eye of the human patient, and wherein the therapeutic product is not an anti-human vascular endothelial growth factor (hVEGF) antibody.

[0081] 14. The method of paragraph 13, wherein the vitrectomy is a partial vitrectomy.

[0082] 15. A method of subretinal administration for treating an ocular condition, comprising administering to the subretinal space of the posterior of the eye of a human subject in need of treatment a recombinant viral vector comprising a nucleotide sequence encoding a therapeutic product, such that the therapeutic product is expressed and the ocular condition is treated, wherein the method does not comprise performing a vitrectomy on the eye of the human patient.

[0083] 16. The method of paragraph 15, wherein the administering step is by intravitreal injection.

[0084] 17. The method of paragraph 16, wherein the intravitreal injection comprises inserting a sharp needle into the sclera via the superior or inferior side of the eye and passing the sharp needle completely through the vitreous body to inject the recombinant viral vector into the subretinal space on the other side.

[0085] 18. The method of paragraph 16, wherein the intravitreal injection comprises inserting a trocar into the sclera and inserting a cannula through the trocar and through the vitreous body to inject the recombinant viral vector into the subretinal space on the other side.

[0086] 19. The method of any one of paragraphs 15-18, wherein the therapeutic product is an anti-hVEGF antibody.

[0087] 20. The method of paragraph 19, wherein the anti-hVEGF antibody is an anti-hVEGF antigen-binding fragment.

[0088] 21. The method of paragraph 20, wherein the anti-hVEGF antigen-binding fragment is a Fab, F(ab')2, or single-chain variable fragment (scFv).

[0089] 22. The method of any one of paragraphs 19-21, wherein the anti-hVEGF antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 2 or SEQ ID NO: 4 and a light chain comprising the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 3.

[0090] 23. The method of any one of paragraphs 19-21, wherein the anti-hVEGF antibody comprises light chain CDRs 1-3 of SEQ ID NO: 14-16 and heavy chain CDRs 1-3 of SEQ ID NO: 17-19 or SEQ ID NO: 20, 18, and 21.

[0091] 24. The method of any one of paragraphs 19-23, wherein the ocular condition is associated with nAMD, dry age-related macular degeneration (dry AMD), retinal vein occlusion (RVO), diabetic macular edema (DME), or diabetic retinopathy (DR).

[0092] 25. The method of any one of paragraphs 19-23, wherein the ocular condition is associated with nAMD.

[0093] 26. The method of any one of paragraphs 1-11 and 13-18, wherein:

[0094] (1) the ocular condition is associated with Batten-CLN1 and the therapeutic product is palmitoyl-protein thioesterase 1 (PPT1);

[0095] (2) the ocular condition is associated with Batten-CLN2 and the therapeutic product is tripeptidyl-peptidase 1 (TPPl);

[0096] (3) the ocular condition is associated with Batten-CLN3 and the therapeutic product is Battenin (CLN3);

[0097] (4) the ocular condition is associated with Batten-CLN6 and the therapeutic product is CLN6 transmembrane ER protein (CLN6);

[0098] (5) the ocular condition is associated with Batten-CLN7 and the therapeutic product is major facilitator superfamily domain containing 8 (MFSD8);

[0099] (6) the ocular condition is associated with Type 1 Arthur syndrome and the therapeutic product is myosin VIIA (MY07A);

[0100] (7) the ocular condition is associated with Type 1 Usher Syndrome, and the therapeutic product is Cadherin-Related 23 (CDH23);

[0101] (8) the ocular condition is associated with Type 2 Usher Syndrome, and the therapeutic product is Protocadherin-Related 15 (PCDH15);

[0102] (9) the ocular condition is associated with Type 2 Usher Syndrome, and the therapeutic product is Usherin (USH2A);

[0103] (10) the ocular condition is associated with Type 3 Usher Syndrome, and the therapeutic product is Clarin 1 (CLRN1);

[0104] (11) the ocular condition is associated with Stargardt Disease, and the therapeutic product is ATP Binding Cassette Subfamily A Member 4 (ABCA4);

[0105] (12) the ocular condition is associated with Stargardt Disease, and the therapeutic product is ELOVL Fatty Acid Elongase 4 (ELOVL4);

[0106] (13) the ocular condition is associated with Uveitis, and the therapeutic product is Anti-Interleukin 6 (IL6) Monoclonal Antibody;

[0107] (14) the ocular condition is associated with Uveitis, and the therapeutic product is Anti-TNF-a (TNF) Monoclonal Antibody;

[0108] (15) the ocular condition is associated with Diabetic Macular Edema (DME), and the therapeutic product is Anti-IL6 Monoclonal Antibody;

[0109] (16) the ocular condition is associated with Red-Green Color Blindness, and the therapeutic product is L Opsin (OPN1LW);

[0110] (17) the ocular condition is associated with Red-Green Color Blindness, and the therapeutic product is M Opsin (OPN1MW);

[0111] (18) the ocular condition is associated with Blue Cone Monochromacy, and the therapeutic product is M Opsin (OPN1MW);

[0112] (19) the ocular condition is associated with Leber Congenital Amaurosis 1 (LCA 1), and the therapeutic product is Retinal Guanylate Cyclase 2D (GUCY2D);

[0113] (20) the ocular condition is associated with Leber congenital amaurosis 2 (LCA 2) and the therapeutic product is retinoid isomerohydrolase RPE65 (RPE65);

[0114] (21) the ocular condition is associated with LCA 3 and the therapeutic product is Sperm formation associated 7 (SPATA7);

[0115] (22) the ocular condition is associated with Leber congenital amaurosis 4 (LCA 4) and the therapeutic product is Aryl hydrocarbon receptor interacting protein-like 1 (AIPL1);

[0116] (23) the ocular condition is associated with Leber congenital amaurosis 5 (LCA 5) and the therapeutic product is Lebercilin (LCA5);

[0117] (24) the ocular condition is associated with Leber congenital amaurosis 6 (LCA 6) and the therapeutic product is RPGR interacting protein 1 (RPGRIP1);

[0118] (25) the ocular condition is associated with Leber congenital amaurosis 7 (LCA 7) and the therapeutic product is Cone-rod homeobox (CRX);

[0119] (26) the ocular condition is associated with Leber congenital amaurosis 8 (LCA 8) and the therapeutic product is Crumbs cell polarity complex component 1 (CRB1);

[0120] (27) the ocular condition is associated with Leber congenital amaurosis 9 (LCA 9) and the therapeutic product is Nicotinamide nucleotide adenylyltransferase 1 (NMNAT1);

[0121] (28) the ocular condition is associated with Leber congenital amaurosis 10 (LCA 10) and the therapeutic product is Centrosomal protein 290 (CEP290);

[0122] (29) the ocular condition is associated with Leber congenital amaurosis 11 (LCA 11) and the therapeutic product is Inosine monophosphate dehydrogenase 1 (IMPDH1);

[0123] (30) the ocular condition is associated with Leber congenital amaurosis 12 (LCA 12) and the therapeutic product is Retinal degeneration 3, GUCY2D regulator (RD3);

[0124] (31) the ocular condition is associated with Leber congenital amaurosis 13 (LCA 13), and the therapeutic product is retinol dehydrogenase 12 (RDH12);

[0125] (32) the ocular condition is associated with Leber congenital amaurosis 14 (LCA 14), and the therapeutic product is lecithin retinol acyltransferase (LRAT);

[0126] (33) the ocular condition is associated with Leber congenital amaurosis 15 (LCA 15), and the therapeutic product is tubby-like protein 1 (TULP1);

[0127] (34) the ocular condition is associated with Leber congenital amaurosis 16 (LCA 16), and the therapeutic product is potassium voltage-gated channel subfamily J member 13 (KCNJ13);

[0128] (35) the ocular condition is associated with Leber’s hereditary optic neuropathy (LHON), and the therapeutic product is mitochondrial encoded NADH dehydrogenase 1 (MT-ND1);

[0129] (36) the ocular condition is associated with LHON, and the therapeutic product is mitochondrial encoded NADH dehydrogenase 4 (MT-ND4);

[0130] (37) the ocular condition is associated with LHON, and the therapeutic product is mitochondrial encoded NADH dehydrogenase 6 (MT-ND6);

[0131] (38) the ocular condition is associated with neuromyelitis optica (NMO), and the therapeutic product is an anti-complement C5 monoclonal antibody;

[0132] (39) the ocular condition is associated with NMO, and the therapeutic product is an anti-IL6 monoclonal antibody;

[0133] (40) the ocular condition is associated with uveitis, and the therapeutic product is an anti-complement C5 monoclonal antibody;

[0134] (41) the ocular condition is associated with uveitis, and the therapeutic product is angiotensin I converting enzyme (ACE);

[0135] (42) the ocular condition is associated with uveitis, and the therapeutic product is interleukin 10 (IL10);

[0136] (43) the ocular condition is associated with uveitis, and the therapeutic product is an anti-TNF monoclonal antibody;

[0137] (44) the ocular condition is associated with choroideremia, and the therapeutic product is Rab Escort Protein 1 (CHM);

[0138] (45) the ocular condition is associated with X-linked retinoschisis (XLRS), and the therapeutic product is Retinoschisin 1 (RS1);

[0139] (46) the ocular condition is associated with Bardet-Biedl Syndrome 1, and the therapeutic product is Bardet-Biedl Syndrome 1 (BBS1);

[0140] (47) the ocular condition is associated with Bardet-Biedl Syndrome 2, and the therapeutic product is Bardet-Biedl Syndrome 2 (BBS2);

[0141] (48) the ocular condition is associated with Bardet-Biedl Syndrome 3, and the therapeutic product is ADP Ribosylation Factor Like GTPase 6 (ARL6);

[0142] (49) the ocular condition is associated with Bardet-Biedl Syndrome 4, and the therapeutic product is Bardet-Biedl Syndrome 4 (BBS4);

[0143] (50) the ocular condition is associated with Bardet-Biedl Syndrome 5, and the therapeutic product is Bardet-Biedl Syndrome 5 (BBS5);

[0144] (51) the ocular condition is associated with Bardet-Biedl Syndrome 6, and the therapeutic product is McKusick-Kaufman Syndrome (MKKS);

[0145] (52) the ocular condition is associated with Bardet-Biedl Syndrome 7, and the therapeutic product is Bardet-Biedl Syndrome 7 (BBS7);

[0146] (53) the ocular condition is associated with Bardet-Biedl Syndrome 8, and the therapeutic product is Tetratricopeptide Repeat Domain 8 (TTC8);

[0147] (54) the ocular condition is associated with Bardet-Biedl Syndrome 9, and the therapeutic product is Bardet-Biedl Syndrome 9 (BBS9);

[0148] (55) the ocular condition is associated with Bardet-Biedl Syndrome 10, and the therapeutic product is Bardet-Biedl Syndrome 10 (BBS10);

[0149] (56) the ocular condition is associated with Bardet-Biedl Syndrome 11, and the therapeutic product is Tripartite motif containing 32 (TRIM32);

[0150] (57) the ocular condition is associated with Bardet-Biedl Syndrome 12, and the therapeutic product is Bardet-Biedl Syndrome 12 (BBS12);

[0151] (58) the ocular condition is associated with Bardet-Biedl Syndrome 13, and the therapeutic product is MKS Transition Zone Complex Subunit 1 (MKS1);

[0152] (59) the ocular condition is associated with Bardet-Biedl Syndrome 14, and the therapeutic product is Centrosomal Protein 290 (CEP290);

[0153] (60) the ocular condition is associated with Bardet-Biedl Syndrome 15, and the therapeutic product is WD Repeat Containing Planar Cell Polarity Effector (WDPCP);

[0154] (61) the ocular condition is associated with Bardet-Biedl Syndrome 16, and the therapeutic product is Serologically Defined Colon Cancer Antigen 8 (SDCCAG8);

[0155] (62) the ocular condition is associated with Bardet-Biedl Syndrome 17, and the therapeutic product is Leucine Zipper Transcription Factor Like 1 (LZTFL1);

[0156] (63) the ocular condition is associated with Bardet-Biedl Syndrome 18, and the therapeutic product is BBSome Interacting Protein 1 (BBIP1);

[0157] (64) the ocular condition is associated with Bardet-Biedl Syndrome 19, and the therapeutic product is Intraflagellar Transport Protein 27 (IFT27);

[0158] (65) the ocular condition is associated with Cone Dystrophy, and the therapeutic product is Guanylate Cyclase Activator 1A (GUCA1A);

[0159] (66) the ocular condition is associated with Optic Atrophy, and the therapeutic product is OPA1 Mitochondrial Motor Protein Like GTPase (OPA1);

[0160] (67) the ocular condition is associated with Retinitis Pigmentosa 1, and the therapeutic product is RP1 Axonal Microtubule Associated (RP1);

[0161] (68) the ocular condition is associated with Retinitis Pigmentosa 2, and the therapeutic product is RP2 Activator of ARL3 GTPase (RP2);

[0162] (69) the ocular condition is associated with retinitis pigmentosa 7, and the therapeutic product is peripheral plasma membrane protein 2 (PRPH2);

[0163] (70) the ocular condition is associated with retinitis pigmentosa 11, and the therapeutic product is pre-mRNA-processing factor 31 (PRPF31);

[0164] (71) the ocular condition is associated with retinitis pigmentosa 12, and the therapeutic product is crumbs cell polarity complex component 1 (CRB1);

[0165] (72) the ocular condition is associated with retinitis pigmentosa 13, and the therapeutic product is pre-mRNA-processing factor 8 (PRPF8);

[0166] (73) the ocular condition is associated with retinitis pigmentosa 25, and the therapeutic product is ocular albinism type 1 homolog (EYS);

[0167] (74) the ocular condition is associated with retinitis pigmentosa 28, and the therapeutic product is FAM161 centrosomal protein A (FAM161A);

[0168] (75) the ocular condition is associated with retinitis pigmentosa 37, and the therapeutic product is nuclear receptor subfamily 2, group E, member 3 (NR2E3);

[0169] (76) the ocular condition is associated with retinitis pigmentosa 38, and the therapeutic product is MER proto-oncogene tyrosine kinase (MERTK);

[0170] (77) the ocular condition is associated with retinitis pigmentosa 40, and the therapeutic product is phosphodiesterase 6B (PDE6B);

[0171] (78) the ocular condition is associated with retinitis pigmentosa 41, and the therapeutic product is prominin 1 (PROM1);

[0172] (79) the ocular condition is associated with retinitis pigmentosa 43, and the therapeutic product is phosphodiesterase 6A (PDE6A);

[0173] (80) the ocular condition is associated with retinitis pigmentosa 56, and the therapeutic product is interphotoreceptor matrix proteoglycan 2 (IMPG2);

[0174] (81) the ocular condition is associated with retinitis pigmentosa 62, and the therapeutic product is male germ cell associated kinase (MAK);

[0175] (82) the ocular condition is associated with retinitis pigmentosa 80, and the therapeutic product is intraflagellar transport 140 (IFT140);

[0176] (83) the ocular condition is associated with dry AMD, and the therapeutic product is an anti-complement C5 monoclonal antibody;

[0177] (84) the ocular condition is associated with dry AMD, and the therapeutic product is an anti-membrane attack complex (MAC) monoclonal antibody;

[0178] (85) the ocular condition is associated with dry AMD, and the therapeutic product is HtrA serine peptidase 1 (HTRA1);

[0179] (86) the ocular condition is associated with Best disease, and the therapeutic product is bestrophin 1 (BEST1);

[0180] (87) the ocular condition is associated with dry AMD, and the therapeutic product is a complement factor B antisense oligonucleotide;

[0181] (88) the ocular condition is associated with dry AMD, and the therapeutic product is an anti-beta-amyloid monoclonal antibody;

[0182] (89) the ocular condition is associated with dry AMD, and the therapeutic product is CD59 glycoprotein (CD59);

[0183] (90) the ocular condition is associated with dry AMD, and the therapeutic product is channelrhodopsin-1 (ChR1);

[0184] (91) the ocular condition is associated with dry AMD, and the therapeutic product is channelrhodopsin-2 (ChR2), a light-sensitive protein found in Chlamydomonas reinhardtii;

[0185] (92) the ocular condition is associated with dry AMD, and the therapeutic product is an anti-complement factor C5a aptamer;

[0186] (93) the ocular condition is associated with dry AMD, and the therapeutic product is an anti-complement factor D monoclonal antibody;

[0187] (94) the ocular condition is associated with age-related retinal ganglion cell (RGC) degeneration, and the therapeutic product is DnaJ heat shock protein family (Hsp40) member C3 (DNAJC3);

[0188] (95) the ocular condition is associated with blue cone monochromacy (BCM), and the therapeutic product is L-opsin (OPN1LW);

[0189] (96) the ocular condition is associated with glaucoma, and the therapeutic product is beta-2 adrenergic receptor siRNA;

[0190] (97) the ocular condition is associated with glaucoma, and the therapeutic product is caspase-2 (CASP2);

[0191] (98) the ocular condition is associated with glaucoma, and the therapeutic product is insulin receptor substrate 1 (IRS1);

[0192] (99) the ocular condition is associated with glaucoma, and the therapeutic product is HIF-1 responsive protein RTP801 (RTP801);

[0193] (100) the ocular condition is associated with glaucoma, and the therapeutic product is transforming growth factor beta 2 (TGFB2);

[0194] (101) the ocular condition is associated with glaucoma, and the therapeutic product is brain-derived neurotrophic factor (BDNF);

[0195] (102) the ocular condition is associated with glaucoma, and the therapeutic product is ciliary neurotrophic factor (CNTF);

[0196] (103) the ocular condition is associated with glaucoma, and the therapeutic product is prostaglandin endoperoxide synthase 2 (PTGS2);

[0197] (104) the ocular condition is associated with glaucoma, and the therapeutic product is prostaglandin F receptor (PTGFR);

[0198] (105) the ocular condition is associated with glaucoma, and the therapeutic product is hyaluronidase;

[0199] (106) the ocular condition is associated with glaucoma, and the therapeutic product is pigment epithelium-derived factor (PEDF);

[0200] (107) the ocular condition is associated with glaucoma, and the therapeutic product is vascular endothelial growth factor (VEGF);

[0201] (108) the ocular condition is associated with glaucoma, and the therapeutic product is placental growth factor (PGF);

[0202] (109) the ocular condition is associated with glaucoma, and the therapeutic product is myocilin (MYOC);

[0203] (110) the ocular condition is associated with NMO, and the therapeutic product is anti-complement C5 monoclonal antibody;

[0204] (111) the ocular condition is associated with NMO, and the therapeutic product is C-C motif chemokine receptor 5 (CCR5) siRNA;

[0205] (112) the ocular condition is associated with NMO, and the therapeutic product is anti-CD19 monoclonal antibody;

[0206] (113) the ocular condition is associated with retinitis pigmentosa associated with rhodopsin mutations, and the therapeutic product is channelrhodopsin-1 (ChRl);

[0207] (114) the ocular condition is associated with retinitis pigmentosa associated with rhodopsin mutations, and the therapeutic product is channelrhodopsin-2 (ChR2);

[0208] (115) the ocular condition is associated with retinitis pigmentosa, and the therapeutic product is ciliary neurotrophic factor (CNTF);

[0209] (116) the ocular condition is associated with autosomal recessive retinitis pigmentosa, and the therapeutic product is crumbs cell polarity complex component 1 (CRBl);

[0210] (117) the ocular condition is associated with autosomal recessive retinitis pigmentosa, and the therapeutic product is crumbs cell polarity complex component 2 (CRB2);

[0211] (118) the ocular condition is associated with retinitis pigmentosa, and the therapeutic product is histone deacetylase 4 (HDAC4);

[0212] (119) the ocular condition is associated with retinitis pigmentosa, and the therapeutic product is rhodopsin (RHO);

[0213] (120) the ocular condition is associated with retinitis pigmentosa, and the therapeutic product is nerve growth factor (NGF);

[0214] (121) the ocular condition is associated with retinitis pigmentosa, and the therapeutic product is nuclear factor erythroid 2-like 2 (NRF2);

[0215] (122) the ocular condition is associated with retinitis pigmentosa, and the therapeutic product is pigment epithelium-derived factor (PEDF);

[0216] (123) the ocular condition is associated with retinitis pigmentosa, and the therapeutic product is glutathione S-transferase PI 1 (GSTP1);

[0217] (124) the ocular condition is associated with retinitis pigmentosa, and the therapeutic product is rod-derived cone viability factor (RDCVF);

[0218] (125) the ocular condition is associated with retinitis pigmentosa, and the therapeutic product is rhodopsin (RHO);

[0219] (126) the ocular condition is associated with retinitis pigmentosa, and the therapeutic product is retinaldehyde binding protein 1 (RLBP1);

[0220] (127) the ocular condition is associated with Stargardt disease, and the therapeutic product is anti-complement C5 aptamer;

[0221] (128) the ocular condition is associated with uveitis, and the therapeutic product is double homeobox 4 (DUX4);

[0222] (129) the ocular condition is associated with uveitis, and the therapeutic product is NLR family, pyrin domain containing 3 (NLRP3);

[0223] (130) the ocular condition is associated with uveitis, and the therapeutic product is spleen associated tyrosine kinase (SYK);

[0224] (131) the ocular condition is associated with uveitis, and the therapeutic product is adrenocorticotropic hormone (ACTH);

[0225] (132) the ocular condition is associated with uveitis, and the therapeutic product is caspase 1 (CASP1);

[0226] (133) the ocular condition is associated with uveitis, and the therapeutic product is anti-CD59 monoclonal antibody;

[0227] (134) the ocular condition is associated with uveitis, and the therapeutic product is anti-complement C5 aptamer;

[0228] (135) the ocular condition is associated with corneal neovascularization, and the therapeutic product is insulin receptor substrate 1 (IRS1);

[0229] (136) the ocular condition is associated with corneal neovascularization and the therapeutic product is NOTCH regulated ankyrin repeat protein (NRARP);

[0230] (137) the ocular condition is associated with diabetic retinopathy and the therapeutic product is NOTCH regulated ankyrin repeat protein (NRARP);

[0231] (138) the ocular condition is associated with diabetic retinopathy and the therapeutic product is alpha-2-antiplasmin (A2AP);

[0232] (139) the ocular condition is associated with diabetic retinopathy and the therapeutic product is plasminogen (PLG);

[0233] (140) the ocular condition is associated with diabetic retinopathy and the therapeutic product is growth hormone;

[0234] (141) the ocular condition is associated with diabetic retinopathy and the therapeutic product is insulin-like growth factor 1 (IGF1);

[0235] (142) the ocular condition is associated with diabetic retinopathy and the therapeutic product is interleukin 1 beta (IL1B);

[0236] (143) the ocular condition is associated with diabetic retinopathy and the therapeutic product is angiotensin I converting enzyme 2 (ACE2);

[0237] (144) the ocular condition is associated with diabetic retinopathy and the therapeutic product is IRS1;

[0238] (145) the ocular condition is associated with diabetic retinopathy and the therapeutic product is anti-integrin oligopeptide;

[0239] (146) the ocular condition is associated with diabetic retinopathy and the therapeutic product is anti-placental growth factor (PGF) monoclonal antibody;

[0240] (147) the ocular condition is associated with Graves ophthalmopathy and the therapeutic product is anti-CD40 monoclonal antibody;

[0241] (148) the ocular condition is associated with Graves ophthalmopathy and the therapeutic product is anti-insulin-like growth factor 1 receptor (IGF1R) monoclonal antibody;

[0242] (149) the ocular condition is associated with Graves Ophthalmopathy, and the therapeutic product is an anti-Insulin-Like Growth Factor 2 Receptor (IGF2R) monoclonal antibody;

[0243] (150) the ocular condition is associated with DME, and the therapeutic product is an anti-integrin oligopeptide;

[0244] (151) the ocular condition is associated with DME, and the therapeutic product is an anti-Placental Growth Factor (PGF) monoclonal antibody;

[0245] (152) the ocular condition is associated with DME, and the therapeutic product is an RTP801 siRNA;

[0246] (153) the ocular condition is associated with vision loss associated with multiple sclerosis (MS), and the therapeutic product is ND1;

[0247] (154) the ocular condition is associated with myopia, and the therapeutic product is Matrix Metalloproteinase 2 (MMP2) RNAi;

[0248] (155) the ocular condition is associated with X-linked recessive ocular albinism, and the therapeutic product is G Protein-Coupled Receptor 143 (GPR143);

[0249] (156) the ocular condition is associated with ocular albinism type 1, and the therapeutic product is Tyrosinase (TYR);

[0250] (157) the ocular condition is associated with optic neuritis, and the therapeutic product is Caspase 2 (CASP2);

[0251] (158) the ocular condition is associated with optic neuritis, and the therapeutic product is an anti-Leucine-Rich Repeat and Ig Domain-Containing Protein 1 (LINGO1) monoclonal antibody; or

[0252] (159) the ocular condition is associated with polypoidal choroidal vasculopathy, and the therapeutic product is an anti-Complement C5 aptamer.

[0253] 27. The method of any one of paragraphs 1-11 and 15-18, wherein:

[0254] (1) the ocular condition is associated with X-linked retinitis pigmentosa (XLRP), and the therapeutic product is Retinitis Pigmentosa GTPase Regulator (RPGR);

[0255] (2) the ocular condition is associated with achromatopsia (ACHM), and the therapeutic product is Cyclic Nucleotide-Gated Channel Beta 3 (CNGB3);

[0256] (3) the ocular condition is associated with achromatopsia, and the therapeutic product is cyclic nucleotide-gated channel alpha 3 (CNGA3); or

[0257] (4) the ocular condition is associated with retinal dystrophy associated with bi-allelic RPE65 mutations, and the therapeutic product is retinoid isomerohydrolase RPE65 (RPE65).

[0258] 28. The method of any of paragraphs 1-11 and 13-18, wherein:

[0259] (1) the ocular condition is associated with Batten-CLN1, and the therapeutic product is palmitoyl-protein thioesterase 1 (PPT1);

[0260] (2) the ocular condition is associated with Batten-CLN2, and the therapeutic product is tripeptidyl-peptidase 1 (TPPl);

[0261] (3) the ocular condition is associated with Batten-CLN3, and the therapeutic product is Battenin (CLN3);

[0262] (4) the ocular condition is associated with uveitis, and the therapeutic product is an anti- interleukin 6 (IL6) monoclonal antibody;

[0263] (5) the ocular condition is associated with uveitis, and the therapeutic product is an anti-TNF-alpha (TNF) monoclonal antibody;

[0264] (6) the ocular condition is associated with diabetic macular edema (DME), and the therapeutic product is an anti-IL6 monoclonal antibody;

[0265] (7) the ocular condition is associated with red-green color blindness, and the therapeutic product is L opsin (OPN1LW);

[0266] (8) the ocular condition is associated with red-green color blindness, and the therapeutic product is M opsin (OPN1MW);

[0267] (9) the ocular condition is associated with blue cone monochromacy, and the therapeutic product is M opsin (OPN1MW);

[0268] (10) the ocular condition is associated with Leber congenital amaurosis 1 (LCA 1), and the therapeutic product is retinal guanylate cyclase 2D (GUCY2D);

[0269] (11) the ocular condition is associated with Leber congenital amaurosis 2 (LCA 2), and the therapeutic product is retinoid isomerohydrolase RPE65 (RPE65);

[0270] (12) the ocular condition is associated with Leber congenital amaurosis 7 (LCA 7), and the therapeutic product is cone-rod homeobox (CRX);

[0271] (13) the ocular condition is associated with Leber congenital amaurosis 11 (LCA 11), and the therapeutic product is inosine monophosphate dehydrogenase 1 (IMPDH1);

[0272] (14) the ocular condition is associated with Leber congenital amaurosis 12 (LCA 12), and the therapeutic product is retinal degeneration 3, GUCY2D regulator (RD3);

[0273] (15) the ocular condition is associated with Leber congenital amaurosis 13 (LCA 13), and the therapeutic product is retinol dehydrogenase 12 (RDH12);

[0274] (16) the ocular condition is associated with Leber congenital amaurosis 15 (LCA 15), and the therapeutic product is tubby-like protein 1 (TULP1);

[0275] (17) the ocular condition is associated with Leber congenital amaurosis 16 (LCA 16), and the therapeutic product is potassium voltage-gated channel subfamily J member 13 (KCNJ13);

[0276] (18) the ocular condition is associated with Leber’s hereditary optic neuropathy (LHON), and the therapeutic product is mitochondrially encoded NADH dehydrogenase 1 (MT-ND1);

[0277] (19) the ocular condition is associated with LHON, and the therapeutic product is mitochondrially encoded NADH dehydrogenase 4 (MT-ND4);

[0278] (20) the ocular condition is associated with LHON, and the therapeutic product is mitochondrially encoded NADH dehydrogenase 6 (MT-ND6);

[0279] (21) the ocular condition is associated with neuromyelitis optica (NMO), and the therapeutic product is an anti-complement C5 monoclonal antibody;

[0280] (22) the ocular condition is associated with NMO, and the therapeutic product is an anti-IL6 monoclonal antibody;

[0281] (23) the ocular condition is associated with uveitis, and the therapeutic product is an anti-complement C5 monoclonal antibody;

[0282] (24) the ocular condition is associated with uveitis, and the therapeutic product is angiotensin I converting enzyme (ACE);

[0283] (25) the ocular condition is associated with uveitis, and the therapeutic product is interleukin 10 (IL10);

[0284] (26) the ocular condition is associated with uveitis, and the therapeutic product is an anti-TNF monoclonal antibody;

[0285] (27) the ocular condition is associated with X-linked retinoschisis (XLRS), and the therapeutic product is retinoschisin (RS1);

[0286] (28) the ocular condition is associated with Bardet-Biedl syndrome 1, and the therapeutic product is Bardet-Biedl syndrome 1 (BBS1);

[0287] (29) the ocular condition is associated with Bardet-Biedl syndrome 3, and the therapeutic product is ADP ribosylation factor-like GTPase 6 (ARL6);

[0288] (30) the ocular condition is associated with Bardet-Biedl syndrome 5, and the therapeutic product is Bardet-Biedl syndrome 5 (BBS5);

[0289] (31) the ocular condition is associated with Bardet-Biedl syndrome 6, and the therapeutic product is McKusick-Kaufman syndrome (MKKS);

[0290] (32) the ocular condition is associated with Bardet-Biedl syndrome 10, and the therapeutic product is Bardet-Biedl syndrome 10 (BBS10);

[0291] (33) the ocular condition is associated with Bardet-Biedl syndrome 11, and the therapeutic product is tripartite motif containing 32 (TRIM32);

[0292] (34) the ocular condition is associated with Bardet-Biedl syndrome 13, and the therapeutic product is MKS transition zone complex subunit 1 (MKS1);

[0293] (35) the ocular condition is associated with Bardet-Biedl syndrome 18, and the therapeutic product is BBSome interacting protein 1 (BBIP1);

[0294] (36) the ocular condition is associated with Bardet-Biedl Syndrome 19, and the therapeutic product is Intraflagellar Transport Protein 27 (IFT27);

[0295] (37) the ocular condition is associated with cone dystrophy, and the therapeutic product is Guanylate Cyclase Activator 1A (GUCA1A);

[0296] (38) the ocular condition is associated with Retinitis Pigmentosa 13, and the therapeutic product is Pre-mRNA Processing Factor 8 (PRPF8);

[0297] (39) the ocular condition is associated with Retinitis Pigmentosa 37, and the therapeutic product is Nuclear Receptor Subfamily 2, Group E, Member 3 (NR2E3); or

[0298] (40) the ocular condition is associated with Best Disease, and the therapeutic product is Bestrophin 1 (BEST1).

[0299] 29. The method of any one of paragraphs 1-11 and 15-18, wherein:

[0300] (1) the ocular condition is associated with retinal dystrophy associated with biallelic RPE65 mutations, and the therapeutic product is Retinoid Isomerohydrolase RPE65 (RPE65).

[0301] 30. The method of any one of paragraphs 1-11 and 13-18, wherein:

[0302] (1) the ocular condition is associated with Batten-CLN2, and the therapeutic product is Tripeptidyl-Peptidase 1 (TPPl);

[0303] (2) the ocular condition is associated with Usher Syndrome Type 1, and the therapeutic product is Myosin VIIA (MY07A);

[0304] (3) the ocular condition is associated with Usher Syndrome Type 1, and the therapeutic product is Cadherin-Related 23 (CDH23);

[0305] (4) the ocular condition is associated with Usher Syndrome Type 2, and the therapeutic product is Protocadherin-Related 15 (PCDH15);

[0306] (5) the ocular condition is associated with Usher Syndrome Type 2, and the therapeutic product is Usherin (USH2A);

[0307] (6) the ocular condition is associated with Usher Syndrome Type 3, and the therapeutic product is Clarin 1 (CLRN1);

[0308] (7) the ocular condition is associated with Stargardt disease and the therapeutic product is ATP binding cassette subfamily A member 4 (ABCA4);

[0309] (8) the ocular condition is associated with Stargardt disease and the therapeutic product is ELOVL fatty acid elongase 4 (ELOVL4);

[0310] (9) the ocular condition is associated with red-green color blindness and the therapeutic product is L opsin (OPN1LW);

[0311] (10) the ocular condition is associated with red-green color blindness and the therapeutic product is M opsin (OPN1MW);

[0312] (11) the ocular condition is associated with blue cone monochromacy and the therapeutic product is M opsin (OPN1MW);

[0313] (12) the ocular condition is associated with Leber congenital amaurosis 1 (LCA 1) and the therapeutic product is retinal guanylate cyclase 2D (GUCY2D);

[0314] (13) the ocular condition is associated with Leber congenital amaurosis 2 (LCA 2) and the therapeutic product is retinal isomerohydrolase RPE65 (RPE65);

[0315] (14) the ocular condition is associated with Leber congenital amaurosis 4 (LCA 4) and the therapeutic product is aryl hydrocarbon receptor interacting protein-like 1 (AIPL1);

[0316] (15) the ocular condition is associated with Leber congenital amaurosis 7 (LCA 7) and the therapeutic product is cone-rod homeobox (CRX);

[0317] (16) the ocular condition is associated with Leber congenital amaurosis 8 (LCA 8) and the therapeutic product is Crumbs cell polarity complex component 1 (CRB1);

[0318] (17) the ocular condition is associated with Leber congenital amaurosis 9 (LCA 9) and the therapeutic product is nicotinamide nucleotide adenylyltransferase 1 (NMNAT1);

[0319] (18) the ocular condition is associated with Leber congenital amaurosis 10 (LCA 10) and the therapeutic product is centrosomal protein 290 (CEP290);

[0320] (19) the ocular condition is associated with Leber congenital amaurosis 11 (LCA 11), and the therapeutic product is inosine monophosphate dehydrogenase 1 (IMPDH1);

[0321] (20) the ocular condition is associated with Leber congenital amaurosis 15 (LCA 15), and the therapeutic product is tubby-like protein 1 (TULP1);

[0322] (21) the ocular condition is associated with LHON, and the therapeutic product is mitochondrial encoded NADH dehydrogenase 4 (MT-ND4);

[0323] (22) the ocular condition is associated with LHON, and the therapeutic product is mitochondrial encoded NADH dehydrogenase 6 (MT-ND6);

[0324] (23) the ocular condition is associated with choroideremia, and the therapeutic product is Rab escort protein 1 (CHM);

[0325] (24) the ocular condition is associated with X-linked retinoschisis (XLRS), and the therapeutic product is retinoschisin 1 (RS1);

[0326] (25) the ocular condition is associated with Bardet-Biedl syndrome 1, and the therapeutic product is Bardet-Biedl syndrome 1 (BBS1);

[0327] (26) the ocular condition is associated with Bardet-Biedl syndrome 6, and the therapeutic product is McKusick-Kaufman syndrome (MKKS);

[0328] (27) the ocular condition is associated with Bardet-Biedl syndrome 10, and the therapeutic product is Bardet-Biedl syndrome 10 (BBS10);

[0329] (28) the ocular condition is associated with cone dystrophy, and the therapeutic product is guanylate cyclase activator 1A (GUCA1A);

[0330] (29) the ocular condition is associated with optic atrophy, and the therapeutic product is OPA1 mitochondrial dynamin-like GTPase (OPA1);

[0331] (30) the ocular condition is associated with retinitis pigmentosa 1, and the therapeutic product is RP1 axonal microtubule associated (RP1);

[0332] (31) the ocular condition is associated with retinitis pigmentosa 2, and the therapeutic product is RP2 activator of ARL3 GTPase (RP2);

[0333] (32) the ocular condition is associated with Retinitis Pigmentosa 7, and the therapeutic product is Peripherin 2 (PRPH2);

[0334] (33) the ocular condition is associated with Retinitis Pigmentosa 11, and the therapeutic product is Pre-mRNA Processing Factor 31 (PRPF31);

[0335] (34) the ocular condition is associated with Retinitis Pigmentosa 13, and the therapeutic product is Pre-mRNA Processing Factor 8 (PRPF8);

[0336] (35) the ocular condition is associated with Retinitis Pigmentosa 37, and the therapeutic product is Nuclear Receptor Subfamily 2, Group E, Member 3 (NR2E3);

[0337] (36) the ocular condition is associated with Retinitis Pigmentosa 38, and the therapeutic product is MER Proto-Oncogene Tyrosine Kinase (MERTK);

[0338] (37) the ocular condition is associated with Retinitis Pigmentosa 40, and the therapeutic product is Phosphodiesterase 6B (PDE6B);

[0339] (38) the ocular condition is associated with Retinitis Pigmentosa 41, and the therapeutic product is Prominin 1 (PROM1);

[0340] (39) the ocular condition is associated with Retinitis Pigmentosa 56, and the therapeutic product is Interphotoreceptor Matrix Proteoglycan 2 (IMPG2);

[0341] (40) the ocular condition is associated with Retinitis Pigmentosa 62, and the therapeutic product is Male Germ Cell Associated Kinase (MAK);

[0342] (41) the ocular condition is associated with Retinitis Pigmentosa 80, and the therapeutic product is Intraflagellar Transport Protein 140 (IFT140); or

[0343] (42) the ocular condition is associated with Best Disease, and the therapeutic product is Bestrophin 1 (BEST1).

[0344] 31. The method of any one of paragraphs 1-11 and 15-18, wherein:

[0345] (1) the ocular condition is associated with X-linked Retinitis Pigmentosa (XLRP), and the therapeutic product is Retinitis Pigmentosa GTPase Regulator (RPGR);

[0346] (2) the eye condition is associated with achromatopsia, and the therapeutic product is cyclic nucleotide-gated channel beta 3 (CNGB3); or

[0347] (3) the eye condition is associated with achromatopsia, and the therapeutic product is cyclic nucleotide-gated channel alpha 3 (CNGA3).

[0348] 32. The method of any one of paragraphs 1-31, wherein the recombinant viral vector further comprises a nucleotide sequence encoding a promoter or an enhancer-promoter, the nucleotide sequence encoding the promoter or the enhancer-promoter being operably linked to the nucleotide sequence encoding the therapeutic product, and wherein the promoter or the enhancer-promoter is:

[0349] (1) a CAG promoter;

[0350] (2) a CBA promoter;

[0351] (3) a CMV promoter;

[0352] (4) a PR1.7 promoter;

[0353] (5) a rhodopsin kinase (GRK1) photoreceptor-specific enhancer-promoter;

[0354] (6) a hCARp promoter;

[0355] (7) a hRKp;

[0356] (8) a cone photoreceptor-specific human arrestin 3 (ARR3) promoter;

[0357] (9) a rhodopsin promoter; or

[0358] (10) a U6 promoter.

[0359] 33. The method of any one of paragraphs 1-11 and 13-15, wherein the recombinant viral vector further comprises a nucleotide sequence encoding a cone-specific promoter, the nucleotide sequence encoding the cone-specific promoter being operably linked to the nucleotide sequence encoding the therapeutic product, and wherein:

[0360] (1) the eye condition is associated with red-green color blindness, and the therapeutic product is L opsin (OPN1LW);

[0361] (2) the eye condition is associated with red-green color blindness, and the therapeutic product is M opsin (OPN1MW);

[0362] (3) the eye condition is associated with blue cone monochromacy, and the therapeutic product is M opsin (OPN1MW).

[0363] (4) the ocular condition is associated with cone dystrophy, and the therapeutic product is Guanylate Cyclase Activator 1A (GUCA1A); or

[0364] (5) the ocular condition is associated with blue cone monochromacy (BCM), and the therapeutic product is L opsin (OPN1LW).

[0365] 34. The method of any one of paragraphs 1-33, wherein the administering step delivers a therapeutically effective amount of the therapeutic product to the retina of the human subject.

[0366] 35. The method of paragraph 34, wherein the therapeutically effective amount of the therapeutic product is produced by human retinal cells of the human subject.

[0367] 36. The method of paragraph 34, wherein the therapeutically effective amount of the therapeutic product is produced by human photoreceptor cells, horizontal cells, bipolar cells, amacrine cells, retinal ganglion cells, and / or retinal pigment epithelial cells in the outer limiting membrane of the human subject.

[0368] 37. The method of paragraph 36, wherein the human photoreceptor cells are cone cells and / or rod cells.

[0369] 38. The method of paragraph 36, wherein the retinal ganglion cells are dwarf cells, umbrella cells, biiayer cells, giant retinal ganglion cells, photosensitive ganglion cells, and / or Muller glial cells.

[0370] 39. The method of any one of paragraphs 1-38, wherein the recombinant viral vector is an rAAV vector.

[0371] 40. The method of paragraph 39, wherein the recombinant viral vector is an rAAV8 vector.

[0372] 41. The method of any one of paragraphs 1-40, further comprising, after the administering step, a step of monitoring ocular post-injection thermal profile of the injected material in the eye using an infrared thermal imager.

[0373] 42. The method of paragraph 41, wherein the infrared thermal imager is a FLIR T530 infrared thermal imager.

[0374] 43. The method of any one of paragraphs 1-43, wherein the recombinant nucleotide expression vector is administered at a dose of about 6.0 x 1011 10 genome copies per eye.

[0375] 44. The method of any of paragraphs 1-43, wherein the recombinant nucleotide expression vector is administered at a dose of about 1.6 x 10 11 genome copies per eye.

[0376] 45. The method of any of paragraphs 1-43, wherein the recombinant nucleotide expression vector is administered at a dose of about 2.5 x 10 11 genome copies per eye.

[0377] 46. The method of any of paragraphs 1-43, wherein the recombinant nucleotide expression vector is administered at a dose of about 5.0 x 10 11 genome copies per eye.

[0378] 47. The method of any of paragraphs 1-43, wherein the recombinant nucleotide expression vector is administered at a dose of about 3.0 x 10 12 genome copies per eye.

[0379] 4.1.2 Group 2

[0380] 1. A method for treating an ocular condition, comprising administering to the subretinal space of an eye of a human subject in need of treatment a recombinant viral vector comprising a nucleotide sequence encoding a therapeutic product, such that the therapeutic product is expressed and the ocular condition is treated, wherein the method does not comprise performing a vitrectomy on the eye of the human patient.

[0381] 2. The method of paragraph 1, wherein the administering step comprises administering the recombinant viral vector therapeutic product to the subretinal space of the eye of the human subject via the suprachoroidal space of the eye of the human subject.

[0382] 3. The method of paragraph 2, wherein the administering step is by use of a subretinal drug delivery device comprising a catheter that is insertable through the suprachoroidal space and towards the posterior pole, a small needle that injects into the subretinal space at the posterior pole.

[0383] 4. The method of paragraph 3, wherein the administering step comprises inserting the catheter of the subretinal drug delivery device through the suprachoroidal space.

[0384] 5. A method for treating an ocular condition, comprising administering to the suprachoroidal space of an eye of a human subject in need of treatment a recombinant viral vector comprising a nucleotide sequence encoding a therapeutic product, such that the therapeutic product is expressed and the ocular condition is treated.

[0385] 6. The method of paragraph 5, wherein the administering step is by injection of the recombinant viral vector into the suprachoroidal space using a suprachoroidal drug delivery device.

[0386] 7. The method of paragraph 5 or 6, wherein the suprachoroidal drug delivery device is a microinjector.

[0387] 8. A method for treating an ocular condition comprising administering to the external surface of the sclera of an eye of a human subject in need of treatment a recombinant viral vector comprising a nucleotide sequence encoding a therapeutic product, such that the therapeutic product is expressed and the ocular condition is treated.

[0388] 9. The method of paragraph 8, wherein the administering step is by use of a juxtascleral drug delivery device comprising a cannula having a tip that can be inserted and held in direct apposition to the surface of the sclera.

[0389] 10. The method of paragraph 9, wherein the administering step comprises inserting and holding the tip of the cannula in direct apposition to the surface of the sclera.

[0390] 11. The method of any one of paragraphs 1-10, wherein the therapeutic product is not an anti-human vascular endothelial growth factor (hVEGF) antibody.

[0391] 12. The method of any one of paragraphs 1-11, wherein the ocular condition is not associated with neovascular age-related macular degeneration (nAMD).

[0392] 13. A method for treating an ocular condition comprising administering to the subretinal space of an eye of a human subject in need of treatment a recombinant viral vector comprising a nucleotide sequence encoding a therapeutic product, such that the therapeutic product is expressed and the ocular condition is treated, wherein the method comprises performing a vitrectomy on the eye of the human patient, and wherein the therapeutic product is not an anti-human vascular endothelial growth factor (hVEGF) antibody.

[0393] 14. The method of paragraph 13, wherein the vitrectomy is a partial vitrectomy.

[0394] 15. A method for treating an ocular condition comprising administering to the subretinal space of the optic disc, fovea, and macular periphery located in the posterior of an eye of a human subject in need of treatment a recombinant viral vector comprising a nucleotide sequence encoding a therapeutic product, such that the therapeutic product is expressed and the ocular condition is treated, wherein the method does not comprise performing a vitrectomy on the eye of the human patient.

[0395] 16. The method of paragraph 15, wherein the administering step is by intravitreal injection.

[0396] 17. The method of paragraph 16, wherein the intravitreal injection comprises inserting a sharp needle into the sclera via the superior or inferior side of the eye and passing the sharp needle completely through the vitreous body to inject the recombinant viral vector into the subretinal space on the other side.

[0397] 18. The method of paragraph 16, wherein the intravitreal injection comprises inserting a trocar into the sclera and inserting a cannula through the trocar and through the vitreous body to inject the recombinant viral vector into the subretinal space on the other side.

[0398] 19. The method of any one of paragraphs 15-18, wherein the therapeutic product is an anti-hVEGF antibody.

[0399] 20. The method of paragraph 19, wherein the anti-hVEGF antibody is an anti-hVEGF antigen-binding fragment.

[0400] 21. The method of paragraph 20, wherein the anti-hVEGF antigen-binding fragment is a Fab, F(ab')2, or single-chain variable fragment (scFv).

[0401] 22. The method of any one of paragraphs 19-21, wherein the anti-hVEGF antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 2 or SEQ ID NO: 4 and a light chain comprising the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 3.

[0402] 23. The method of any one of paragraphs 19-21, wherein the anti-hVEGF antibody comprises light chain CDRs 1-3 of SEQ ID NO: 14-16 and heavy chain CDRs 1-3 of SEQ ID NO: 17-19 or SEQ ID NO: 20, 18, and 21.

[0403] 24. The method of any one of paragraphs 19-23, wherein the ocular condition is associated with nAMD, dry age-related macular degeneration (dry AMD), retinal vein occlusion (RVO), diabetic macular edema (DME), or diabetic retinopathy (DR).

[0404] 25. The method of any one of paragraphs 19-23, wherein the ocular condition is associated with nAMD.

[0405] 26. The method of any one of paragraphs 1-11 and 13-18, wherein:

[0406] (1) the ocular pathology is associated with Batten-CLN1 and the therapeutic product is palmitoyl-protein thioesterase 1 (PPT1);

[0407] (2) the ocular pathology is associated with Batten-CLN2 and the therapeutic product is tripeptidyl- peptidase 1 (TPPl);

[0408] (3) the ocular pathology is associated with Batten-CLN3 and the therapeutic product is Battenin (CLN3);

[0409] (4) the ocular pathology is associated with Batten-CLN6 and the therapeutic product is CLN6 transmembrane ER protein (CLN6);

[0410] (5) the ocular pathology is associated with Batten-CLN7 and the therapeutic product is major facilitator superfamily domain containing 8 (MFSD8);

[0411] (6) the ocular pathology is associated with Type 1 Usher Syndrome and the therapeutic product is myosin VIIA (MY07A);

[0412] (7) the ocular pathology is associated with Type 1 Usher Syndrome and the therapeutic product is cadherin-related 23 (CDH23);

[0413] (8) the ocular pathology is associated with Type 2 Usher Syndrome and the therapeutic product is protocadherin-related 15 (PCDH15);

[0414] (9) the ocular pathology is associated with Type 2 Usher Syndrome and the therapeutic product is Usherin (USH2A);

[0415] (10) the ocular pathology is associated with Type 3 Usher Syndrome and the therapeutic product is Clarin 1 (CLRN1);

[0416] (11) the ocular pathology is associated with Stargardt Disease and the therapeutic product is ATP binding cassette subfamily A member 4 (ABCA4);

[0417] (12) the ocular pathology is associated with Stargardt Disease and the therapeutic product is ELOVL fatty acid elongase 4 (ELOVL4);

[0418] (13) the ocular pathology is associated with Uveitis and the therapeutic product is anti- interleukin 6 (IL6) monoclonal antibody;

[0419] (14) the ocular condition is associated with uveitis, and the therapeutic product is an anti-TNF-alpha (TNF) monoclonal antibody;

[0420] (15) the ocular condition is associated with diabetic macular edema (DME), and the therapeutic product is an anti-IL6 monoclonal antibody;

[0421] (16) the ocular condition is associated with red-green color blindness, and the therapeutic product is L opsin (OPN1LW);

[0422] (17) the ocular condition is associated with red-green color blindness, and the therapeutic product is M opsin (OPN1MW);

[0423] (18) the ocular condition is associated with blue cone monochromacy, and the therapeutic product is M opsin (OPN1MW);

[0424] (19) the ocular condition is associated with Leber congenital amaurosis 1 (LCA 1), and the therapeutic product is retinal guanylate cyclase 2D (GUCY2D);

[0425] (20) the ocular condition is associated with Leber congenital amaurosis 2 (LCA 2), and the therapeutic product is retinoid isomerohydrolase RPE65 (RPE65);

[0426] (21) the ocular condition is associated with LCA 3, and the therapeutic product is sperm formation associated 7 (SPATA7);

[0427] (22) the ocular condition is associated with Leber congenital amaurosis 4 (LCA 4), and the therapeutic product is aryl hydrocarbon receptor interacting protein-like 1 (AIPL1);

[0428] (23) the ocular condition is associated with Leber congenital amaurosis 5 (LCA 5), and the therapeutic product is Lebercilin (LCA5);

[0429] (24) the ocular condition is associated with Leber congenital amaurosis 6 (LCA 6), and the therapeutic product is RPGR interacting protein 1 (RPGRIP1);

[0430] (25) the ocular condition is associated with Leber congenital amaurosis 7 (LCA 7), and the therapeutic product is cone-rod homeobox (CRX);

[0431] (26) the ocular condition is associated with Leber congenital amaurosis 8 (LCA 8), and the therapeutic product is Crumbs cell polarity complex component 1 (CRB1);

[0432] (27) the ocular condition is associated with Leber congenital amaurosis 9 (LCA 9), and the therapeutic product is nicotinamide nucleotide adenylyltransferase 1 (NMNAT1);

[0433] (28) the ocular condition is associated with Leber congenital amaurosis 10 (LCA 10), and the therapeutic product is centrosomal protein 290 (CEP290);

[0434] (29) the ocular condition is associated with Leber congenital amaurosis 11 (LCA 11), and the therapeutic product is inosine monophosphate dehydrogenase 1 (IMPDH1);

[0435] (30) the ocular condition is associated with Leber congenital amaurosis 12 (LCA 12), and the therapeutic product is retinal degeneration 3, GUCY2D regulator (RD3);

[0436] (31) the ocular condition is associated with Leber congenital amaurosis 13 (LCA 13), and the therapeutic product is retinol dehydrogenase 12 (RDH12);

[0437] (32) the ocular condition is associated with Leber congenital amaurosis 14 (LCA 14), and the therapeutic product is lecithin retinol acyltransferase (LRAT);

[0438] (33) the ocular condition is associated with Leber congenital amaurosis 15 (LCA 15), and the therapeutic product is tubby-like protein 1 (TULP1);

[0439] (34) the ocular condition is associated with Leber congenital amaurosis 16 (LCA 16), and the therapeutic product is potassium voltage-gated channel subfamily J member 13 (KCNJ13);

[0440] (35) the ocular condition is associated with Leber’s hereditary optic neuropathy (LHON), and the therapeutic product is mitochondrially encoded NADH dehydrogenase 1 (MT-ND1);

[0441] (36) the ocular condition is associated with LHON, and the therapeutic product is mitochondrially encoded NADH dehydrogenase 4 (MT-ND4);

[0442] (37) the ocular condition is associated with LHON, and the therapeutic product is mitochondrially encoded NADH dehydrogenase 6 (MT-ND6);

[0443] (38) the ocular condition is associated with neuromyelitis optica (NMO), and the therapeutic product is an anti-complement C5 monoclonal antibody;

[0444] (39) the ocular condition is associated with NMO, and the therapeutic product is an anti-IL6 monoclonal antibody;

[0445] (40) the ocular condition is associated with uveitis, and the therapeutic product is an anti-complement C5 monoclonal antibody;

[0446] (41) the ocular condition is associated with uveitis, and the therapeutic product is angiotensin I converting enzyme (ACE);

[0447] (42) the ocular condition is associated with uveitis, and the therapeutic product is interleukin 10 (IL10);

[0448] (43) the ocular condition is associated with uveitis, and the therapeutic product is an anti-TNF monoclonal antibody;

[0449] (44) the ocular condition is associated with choroideremia, and the therapeutic product is Rab chaperone 1 (CHM);

[0450] (45) the ocular condition is associated with X-linked retinoschisis (XLRS), and the therapeutic product is retinoschisin (RS1);

[0451] (46) the ocular condition is associated with Bardet-Biedl syndrome 1, and the therapeutic product is Bardet-Biedl syndrome 1 (BBS1);

[0452] (47) the ocular condition is associated with Bardet-Biedl syndrome 2, and the therapeutic product is Bardet-Biedl syndrome 2 (BBS2);

[0453] (48) the ocular condition is associated with Bardet-Biedl syndrome 3, and the therapeutic product is ADP ribosylation factor-like GTPase 6 (ARL6);

[0454] (49) the ocular condition is associated with Bardet-Biedl syndrome 4, and the therapeutic product is Bardet-Biedl syndrome 4 (BBS4);

[0455] (50) the ocular condition is associated with Bardet-Biedl syndrome 5, and the therapeutic product is Bardet-Biedl syndrome 5 (BBS5);

[0456] (51) the ocular condition is associated with Bardet-Biedl syndrome 6, and the therapeutic product is McKusick-Kaufman syndrome (MKKS);

[0457] (52) the ocular condition is associated with Bardet-Biedl Syndrome 7, and the therapeutic product is Bardet-Biedl Syndrome 7 (BBS7);

[0458] (53) the ocular condition is associated with Bardet-Biedl Syndrome 8, and the therapeutic product is Tetranectin Repeat Domain 8 (TTC8);

[0459] (54) the ocular condition is associated with Bardet-Biedl Syndrome 9, and the therapeutic product is Bardet-Biedl Syndrome 9 (BBS9);

[0460] (55) the ocular condition is associated with Bardet-Biedl Syndrome 10, and the therapeutic product is Bardet-Biedl Syndrome 10 (BBS10);

[0461] (56) the ocular condition is associated with Bardet-Biedl Syndrome 11, and the therapeutic product is Tripartite motif containing 32 (TRIM32);

[0462] (57) the ocular condition is associated with Bardet-Biedl Syndrome 12, and the therapeutic product is Bardet-Biedl Syndrome 12 (BBS12);

[0463] (58) the ocular condition is associated with Bardet-Biedl Syndrome 13, and the therapeutic product is MKS Transition Zone Complex Subunit 1 (MKS1);

[0464] (59) the ocular condition is associated with Bardet-Biedl Syndrome 14, and the therapeutic product is Centrosomal Protein 290 (CEP290);

[0465] (60) the ocular condition is associated with Bardet-Biedl Syndrome 15, and the therapeutic product is WD Repeat Containing Planar Cell Polarity Effector (WDPCP);

[0466] (61) the ocular condition is associated with Bardet-Biedl Syndrome 16, and the therapeutic product is Serologically Defined Colon Cancer Antigen 8 (SDCCAG8);

[0467] (62) the ocular condition is associated with Bardet-Biedl Syndrome 17, and the therapeutic product is Leucine Zipper Transcription Factor Like 1 (LZTFL1);

[0468] (63) the ocular condition is associated with Bardet-Biedl Syndrome 18, and the therapeutic product is BBSome Interacting Protein 1 (BBIP1);

[0469] (64) The ocular symptoms are associated with Bader-Bid syndrome 19 and the therapeutic product is intraciliary transporter 27 (IFT27);

[0470] (65) The eye condition is related to cone cell malnutrition, and the therapeutic product is guanylate cyclase activator 1A (GUCA1A).

[0471] (66) The eye condition is associated with optic nerve atrophy, and the therapeutic product is OPA1 mitochondrial activator-like GTPase (OPA1);

[0472] (67) The ocular condition is associated with retinitis pigmentosa 1, and the therapeutic product is RP1 axonal microtubule associated (RP1);

[0473] (68) The ocular condition is related to retinitis pigmentosa 2, and the therapeutic product is RP2 activator of ARL3 GTPase (RP2).

[0474] (69) The ocular condition is related to retinitis pigmentosa 7, and the therapeutic product is peripheral protein 2 (PRPH2);

[0475] (70) The ocular symptom is associated with retinitis pigmentosa 11, and the therapeutic product is a precursor mRNA processing factor 31 (PRPF31).

[0476] (71) The ocular condition is associated with retinitis pigmentosa 12 and the therapeutic product is Crumbs cell polar complex component 1 (CRB1).

[0477] (72) The ocular symptoms are associated with retinitis pigmentosa 13, and the therapeutic product is a precursor mRNA processing factor 8 (PRPF8).

[0478] (73) The ocular condition is associated with retinitis pigmentosa 25 and the therapeutic product is an eye-closed homolog (EYS);

[0479] (74) The ocular condition is associated with retinitis pigmentosa 28 and the therapeutic product is FAM161 centrosomal protein A (FAM161A);

[0480] (75) The ocular condition is associated with retinitis pigmentosa 37 and the therapeutic product is a nuclear receptor subfamily 2 E member 3 (NR2E3);

[0481] (76) The ocular condition is associated with retinitis pigmentosa 38 and the therapeutic product is MER proto-oncogene tyrosine kinase (MERTK);

[0482] (77) the ocular condition is associated with retinitis pigmentosa 40, and the therapeutic product is Phosphodiesterase 6B (PDE6B);

[0483] (78) the ocular condition is associated with retinitis pigmentosa 41, and the therapeutic product is Prominin 1 (PROM1);

[0484] (79) the ocular condition is associated with retinitis pigmentosa 43, and the therapeutic product is Phosphodiesterase 6A (PDE6A);

[0485] (80) the ocular condition is associated with retinitis pigmentosa 56, and the therapeutic product is Interphotoreceptor Matrix Proteoglycan 2 (IMPG2);

[0486] (81) the ocular condition is associated with retinitis pigmentosa 62, and the therapeutic product is Male germ cell associated kinase (MAK);

[0487] (82) the ocular condition is associated with retinitis pigmentosa 80, and the therapeutic product is Intraflagellar Transport Protein 140 (IFT140);

[0488] (83) the ocular condition is associated with dry AMD, and the therapeutic product is an anti-complement C5 monoclonal antibody;

[0489] (84) the ocular condition is associated with dry AMD, and the therapeutic product is an anti-Membrane Attack Complex (MAC) monoclonal antibody;

[0490] (85) the ocular condition is associated with dry AMD, and the therapeutic product is HtrA Serine Peptidase 1 (HTRA1);

[0491] (86) the ocular condition is associated with Best disease, and the therapeutic product is Bestrophin 1 (BEST1);

[0492] (87) the ocular condition is associated with dry AMD, and the therapeutic product is a complement factor B antisense oligonucleotide;

[0493] (88) the ocular condition is associated with dry AMD, and the therapeutic product is an anti-beta-amyloid monoclonal antibody;

[0494] (89) the ocular condition is associated with dry AMD, and the therapeutic product is CD59 glycoprotein (CD59);

[0495] (90) the eye condition is associated with dry AMD, and the therapeutic product is channelrhodopsin-1 (ChRl);

[0496] (91) the eye condition is associated with dry AMD, and the therapeutic product is channelrhodopsin-2 (ChR2), a light-sensitive protein found in Chlamydomonas reinhardtii;

[0497] (92) the eye condition is associated with dry AMD, and the therapeutic product is an anti-complement factor C5a aptamer;

[0498] (93) the eye condition is associated with dry AMD, and the therapeutic product is an anti-complement factor D monoclonal antibody;

[0499] (94) the eye condition is associated with age-related retinal ganglion cell (RGC) degeneration, and the therapeutic product is DnaJ heat shock protein family (Hsp40) member C3 (DNAJC3);

[0500] (95) the eye condition is associated with blue cone monochromacy (BCM), and the therapeutic product is L opsin (OPN1LW);

[0501] (96) the eye condition is associated with glaucoma, and the therapeutic product is a beta-2 adrenergic receptor siRNA;

[0502] (97) the eye condition is associated with glaucoma, and the therapeutic product is caspase-2 (CASP2);

[0503] (98) the eye condition is associated with glaucoma, and the therapeutic product is insulin receptor substrate 1 (IRS1);

[0504] (99) the eye condition is associated with glaucoma, and the therapeutic product is HIF-1 responsive protein RTP801 (RTP801);

[0505] (100) the eye condition is associated with glaucoma, and the therapeutic product is transforming growth factor beta 2 (TGFB2);

[0506] (101) the eye condition is associated with glaucoma, and the therapeutic product is brain-derived neurotrophic factor (BDNF);

[0507] (102) the eye condition is associated with glaucoma, and the therapeutic product is ciliary neurotrophic factor (CNTF);

[0508] (103) the ocular condition is associated with glaucoma, and the therapeutic product is prostaglandin endoperoxide synthase 2 (PTGS2);

[0509] (104) the ocular condition is associated with glaucoma, and the therapeutic product is prostaglandin F receptor (PTGFR);

[0510] (105) the ocular condition is associated with glaucoma, and the therapeutic product is hyaluronidase;

[0511] (106) the ocular condition is associated with glaucoma, and the therapeutic product is pigment epithelium-derived factor (PEDF);

[0512] (107) the ocular condition is associated with glaucoma, and the therapeutic product is vascular endothelial growth factor (VEGF);

[0513] (108) the ocular condition is associated with glaucoma, and the therapeutic product is placental growth factor (PGF);

[0514] (109) the ocular condition is associated with glaucoma, and the therapeutic product is myocilin (MYOC);

[0515] (110) the ocular condition is associated with NMO, and the therapeutic product is an anti-complement C5 monoclonal antibody;

[0516] (111) the ocular condition is associated with NMO, and the therapeutic product is a C-C motif chemokine receptor 5 (CCR5) siRNA;

[0517] (112) the ocular condition is associated with NMO, and the therapeutic product is an anti-CD19 monoclonal antibody;

[0518] (113) the ocular condition is associated with retinitis pigmentosa associated with mutations in rhodopsin, and the therapeutic product is channelrhodopsin-1 (ChRl);

[0519] (114) the ocular condition is associated with retinitis pigmentosa associated with mutations in rhodopsin, and the therapeutic product is channelrhodopsin-2 (ChR2);

[0520] (115) the ocular condition is associated with retinitis pigmentosa, and the therapeutic product is ciliary neurotrophic factor (CNTF);

[0521] (116) the ocular condition is associated with autosomal recessive retinitis pigmentosa, and the therapeutic product is Crumbs cell polarity complex component 1 (CRBl);

[0522] (117) the ocular condition is associated with autosomal recessive retinitis pigmentosa, and the therapeutic product is Crumbs cell polarity complex component 2 (CRB2);

[0523] (118) the ocular condition is associated with retinitis pigmentosa, and the therapeutic product is histone deacetylase 4 (HDAC4);

[0524] (119) the ocular condition is associated with retinitis pigmentosa, and the therapeutic product is rhodopsin (RHO);

[0525] (120) the ocular condition is associated with retinitis pigmentosa, and the therapeutic product is nerve growth factor (NGF);

[0526] (121) the ocular condition is associated with retinitis pigmentosa, and the therapeutic product is nuclear factor, erythroid 2-like 2 (NRF2);

[0527] (122) the ocular condition is associated with retinitis pigmentosa, and the therapeutic product is pigment epithelium-derived factor (PEDF);

[0528] (123) the ocular condition is associated with retinitis pigmentosa, and the therapeutic product is glutathione S-transferase PI 1 (GSTP1);

[0529] (124) the ocular condition is associated with retinitis pigmentosa, and the therapeutic product is rod-derived cone viability factor (RDCVF);

[0530] (125) the ocular condition is associated with retinitis pigmentosa, and the therapeutic product is rhodopsin (RHO);

[0531] (126) the ocular condition is associated with retinitis pigmentosa, and the therapeutic product is retinaldehyde binding protein 1 (RLBP1);

[0532] (127) the ocular condition is associated with Stargardt disease, and the therapeutic product is an anti-complement C5 aptamer;

[0533] (128) the ocular condition is associated with uveitis, and the therapeutic product is double homeobox 4 (DUX4);

[0534] (129) the ocular condition is associated with uveitis, and the therapeutic product is NLR family, pyrin domain containing 3 (NLRP3);

[0535] (130) the ocular condition is associated with uveitis, and the therapeutic product is spleen associated tyrosine kinase (SYK);

[0536] (131) the ocular condition is associated with uveitis, and the therapeutic product is adrenocorticotropic hormone (ACTH);

[0537] (132) the ocular condition is associated with uveitis, and the therapeutic product is caspase 1 (CASP1);

[0538] (133) the ocular condition is associated with uveitis, and the therapeutic product is anti-CD59 monoclonal antibody;

[0539] (134) the ocular condition is associated with uveitis, and the therapeutic product is anti-complement C5 aptamer;

[0540] (135) the ocular condition is associated with corneal neovascularization, and the therapeutic product is insulin receptor substrate 1 (IRS1);

[0541] (136) the ocular condition is associated with corneal neovascularization, and the therapeutic product is NOTCH regulated ankyrin repeat protein (NRARP);

[0542] (137) the ocular condition is associated with diabetic retinopathy, and the therapeutic product is NOTCH regulated ankyrin repeat protein (NRARP);

[0543] (138) the ocular condition is associated with diabetic retinopathy, and the therapeutic product is alpha-2-antiplasmin (A2AP);

[0544] (139) the ocular condition is associated with diabetic retinopathy, and the therapeutic product is plasminogen (PLG);

[0545] (140) the ocular condition is associated with diabetic retinopathy, and the therapeutic product is growth hormone;

[0546] (141) the ocular condition is associated with diabetic retinopathy, and the therapeutic product is insulin-like growth factor 1 (IGF1);

[0547] (142) the ocular condition is associated with diabetic retinopathy, and the therapeutic product is interleukin 1 beta (IL1B);

[0548] (143) the ocular condition is associated with diabetic retinopathy, and the therapeutic product is angiotensin I converting enzyme 2 (ACE2);

[0549] (144) the ocular condition is associated with diabetic retinopathy, and the therapeutic product is IRS1;

[0550] (145) the ocular condition is associated with diabetic retinopathy, and the therapeutic product is anti-integrin oligopeptide;

[0551] (146) the ocular condition is associated with diabetic retinopathy, and the therapeutic product is anti-Placental Growth Factor (PGF) monoclonal antibody;

[0552] (147) the ocular condition is associated with Graves Ophthalmopathy, and the therapeutic product is anti-CD40 monoclonal antibody;

[0553] (148) the ocular condition is associated with Graves Ophthalmopathy, and the therapeutic product is anti-Insulin-like Growth Factor 1 Receptor (IGF1R) monoclonal antibody;

[0554] (149) the ocular condition is associated with Graves Ophthalmopathy, and the therapeutic product is anti-Insulin-like Growth Factor 2 Receptor (IGF2R) monoclonal antibody;

[0555] (150) the ocular condition is associated with DME, and the therapeutic product is anti-integrin oligopeptide;

[0556] (151) the ocular condition is associated with DME, and the therapeutic product is anti-Placental Growth Factor (PGF) monoclonal antibody;

[0557] (152) the ocular condition is associated with DME, and the therapeutic product is RTP801 siRNA;

[0558] (153) the ocular condition is associated with vision loss associated with multiple sclerosis (MS), and the therapeutic product is ND1;

[0559] (154) the ocular condition is associated with myopia, and the therapeutic product is Matrix Metalloproteinase 2 (MMP2) RNAi;

[0560] (155) the ocular condition is associated with X-linked recessive ocular albinism, and the therapeutic product is G Protein-Coupled Receptor 143 (GPR143);

[0561] (156) the ocular condition is associated with ocular albinism type 1, and the therapeutic product is Tyrosinase (TYR);

[0562] (157) the ocular condition is associated with optic neuritis, and the therapeutic product is Caspase 2 (CASP2);

[0563] (158) the ocular condition is associated with optic neuritis, and the therapeutic product is Anti-LRRN1 Ig domain-containing Repeats and Ig domain-containing Protein 1 (LINGO1) monoclonal antibody; or

[0564] (159) the ocular condition is associated with polypoidal choroidal vasculopathy, and the therapeutic product is Anti-C5 aptamer.

[0565] 27. The method of any of paragraphs 1-11 and 15-18, wherein:

[0566] (1) the ocular condition is associated with X-linked retinitis pigmentosa (XLRP), and the therapeutic product is Retinitis Pigmentosa GTPase Regulator (RPGR);

[0567] (2) the ocular condition is associated with achromatopsia (ACHM), and the therapeutic product is Cyclic Nucleotide Gated Channel Beta 3 (CNGB3);

[0568] (3) the ocular condition is associated with achromatopsia, and the therapeutic product is Cyclic Nucleotide Gated Channel Alpha 3 (CNGA3); or

[0569] (4) the ocular condition is associated with retinal dystrophy associated with biallelic RPE65 mutations, and the therapeutic product is Retinoid Isomerohydrolase RPE65 (RPE65).

[0570] 28. The method of any of paragraphs 1-11 and 13-18, wherein:

[0571] (1) the ocular condition is associated with Batten-CLN1, and the therapeutic product is Palmitoyl-protein Thioesterase 1 (PPT1);

[0572] (2) the ocular condition is associated with Batten-CLN2, and the therapeutic product is Tripeptidyl-peptidase 1 (TPPl);

[0573] (3) the ocular condition is associated with Batten-CLN3, and the therapeutic product is Battenin (CLN3);

[0574] (4) the ocular condition is associated with uveitis, and the therapeutic product is Anti-Interleukin 6 (IL6) monoclonal antibody;

[0575] (5) the ocular condition is associated with uveitis, and the therapeutic product is an anti-TNF-alpha (TNF) monoclonal antibody;

[0576] (6) the ocular condition is associated with diabetic macular edema (DME), and the therapeutic product is an anti-IL6 monoclonal antibody;

[0577] (7) the ocular condition is associated with red-green color blindness, and the therapeutic product is L opsin (OPN1LW);

[0578] (8) the ocular condition is associated with red-green color blindness, and the therapeutic product is M opsin (OPN1MW);

[0579] (9) the ocular condition is associated with blue cone monochromacy, and the therapeutic product is M opsin (OPN1MW);

[0580] (10) the ocular condition is associated with Leber congenital amaurosis 1 (LCA 1), and the therapeutic product is retinal guanylate cyclase 2D (GUCY2D);

[0581] (11) the ocular condition is associated with Leber congenital amaurosis 2 (LCA 2), and the therapeutic product is retinal isomerohydrolase RPE65 (RPE65);

[0582] (12) the ocular condition is associated with Leber congenital amaurosis 7 (LCA 7), and the therapeutic product is cone-rod homeobox (CRX);

[0583] (13) the ocular condition is associated with Leber congenital amaurosis 11 (LCA 11), and the therapeutic product is inosine monophosphate dehydrogenase 1 (IMPDH1);

[0584] (14) the ocular condition is associated with Leber congenital amaurosis 12 (LCA 12), and the therapeutic product is retinal degeneration 3, GUCY2D regulator (RD3);

[0585] (15) the ocular condition is associated with Leber congenital amaurosis 13 (LCA 13), and the therapeutic product is retinol dehydrogenase 12 (RDH12);

[0586] (16) the ocular condition is associated with Leber congenital amaurosis 15 (LCA 15), and the therapeutic product is tubby-like protein 1 (TULP1);

[0587] (17) the ocular condition is associated with Leber congenital amaurosis 16 (LCA 16), and the therapeutic product is potassium voltage-gated channel subfamily J member 13 (KCNJ13);

[0588] (18) the ocular condition is associated with Leber hereditary optic neuropathy (LHON), and the therapeutic product is Mitochondrially encoded NADH dehydrogenase 1 (MT-ND1);

[0589] (19) the ocular condition is associated with LHON, and the therapeutic product is Mitochondrially encoded NADH dehydrogenase 4 (MT-ND4);

[0590] (20) the ocular condition is associated with LHON, and the therapeutic product is Mitochondrially encoded NADH dehydrogenase 6 (MT-ND6);

[0591] (21) the ocular condition is associated with Neuromyelitis optica (NMO), and the therapeutic product is an anti-complement C5 monoclonal antibody;

[0592] (22) the ocular condition is associated with NMO, and the therapeutic product is an anti-IL6 monoclonal antibody;

[0593] (23) the ocular condition is associated with Uveitis, and the therapeutic product is an anti-complement C5 monoclonal antibody;

[0594] (24) the ocular condition is associated with Uveitis, and the therapeutic product is angiotensin I converting enzyme (ACE);

[0595] (25) the ocular condition is associated with Uveitis, and the therapeutic product is interleukin 10 (IL10);

[0596] (26) the ocular condition is associated with Uveitis, and the therapeutic product is an anti-TNF monoclonal antibody;

[0597] (27) the ocular condition is associated with X-linked retinoschisis (XLRS), and the therapeutic product is retinoschisin (RS1);

[0598] (28) the ocular condition is associated with Bardet-Biedl syndrome 1, and the therapeutic product is Bardet-Biedl syndrome 1 (BBS1);

[0599] (29) the ocular condition is associated with Bardet-Biedl syndrome 3, and the therapeutic product is ADP ribosylation factor like GTPase 6 (ARL6);

[0600] (30) the ocular condition is associated with Bardet-Biedl Syndrome 5, and the therapeutic product is Bardet-Biedl Syndrome 5 (BBS5);

[0601] (31) the ocular condition is associated with Bardet-Biedl Syndrome 6, and the therapeutic product is McKusick-Kaufman Syndrome (MKKS);

[0602] (32) the ocular condition is associated with Bardet-Biedl Syndrome 10, and the therapeutic product is Bardet-Biedl Syndrome 10 (BBS10);

[0603] (33) the ocular condition is associated with Bardet-Biedl Syndrome 11, and the therapeutic product is Tripartite motif containing 32 (TRIM32);

[0604] (34) the ocular condition is associated with Bardet-Biedl Syndrome 13, and the therapeutic product is MKS transition zone complex subunit 1 (MKS1);

[0605] (35) the ocular condition is associated with Bardet-Biedl Syndrome 18, and the therapeutic product is BBSome interacting protein 1 (BBIP1);

[0606] (36) the ocular condition is associated with Bardet-Biedl Syndrome 19, and the therapeutic product is Intraflagellar transport protein 27 (IFT27);

[0607] (37) the ocular condition is associated with Cone Dystrophy, and the therapeutic product is Guanylate cyclase activator 1A (GUCA1A);

[0608] (38) the ocular condition is associated with Retinitis Pigmentosa 13, and the therapeutic product is Pre-mRNA processing factor 8 (PRPF8);

[0609] (39) the ocular condition is associated with Retinitis Pigmentosa 37, and the therapeutic product is Nuclear receptor subfamily 2 group E member 3 (NR2E3); or

[0610] (40) the ocular condition is associated with Best disease, and the therapeutic product is Bestrophin 1 (BEST1).

[0611] 29. The method of any one of paragraphs 1-11 and 15-18, wherein:

[0612] (1) the ocular condition is associated with retinal dystrophy associated with biallelic RPE65 mutations, and the therapeutic product is retinoid isomerohydrolase RPE65 (RPE65).

[0613] 30. The method of any of paragraphs 1-11 and 13-18, wherein:

[0614] (1) the eye condition is associated with Batten-CLN2 and the therapeutic product is tripeptidyl- peptidase 1 (TPPl);

[0615] (2) the eye condition is associated with Type 1 Usher Syndrome and the therapeutic product is myosin VIIA (MY07A);

[0616] (3) the eye condition is associated with Type 1 Usher Syndrome and the therapeutic product is cadherin-related 23 (CDH23);

[0617] (4) the eye condition is associated with Type 2 Usher Syndrome and the therapeutic product is protocadherin-related 15 (PCDH15);

[0618] (5) the eye condition is associated with Type 2 Usher Syndrome and the therapeutic product is Usherin (USH2A);

[0619] (6) the eye condition is associated with Type 3 Usher Syndrome and the therapeutic product is Clarin 1 (CLRN1);

[0620] (7) the eye condition is associated with Stargardt Disease and the therapeutic product is ATP-binding cassette subfamily A member 4 (ABCA4);

[0621] (8) the eye condition is associated with Stargardt Disease and the therapeutic product is ELOVL fatty acid elongase 4 (ELOVL4);

[0622] (9) the eye condition is associated with Red-Green Color Blindness and the therapeutic product is L opsin (OPN1LW);

[0623] (10) the eye condition is associated with Red-Green Color Blindness and the therapeutic product is M opsin (OPN1MW);

[0624] (11) the eye condition is associated with Blue Cone Monochromacy and the therapeutic product is M opsin (OPN1MW);

[0625] (12) the eye condition is associated with Leber Congenital Amaurosis 1 (LCA 1) and the therapeutic product is retinal guanylate cyclase 2D (GUCY2D);

[0626] (13) the ocular condition is associated with Leber congenital amaurosis 2 (LCA 2), and the therapeutic product is retinoid isomerohydrolase RPE65 (RPE65);

[0627] (14) the ocular condition is associated with Leber congenital amaurosis 4 (LCA 4), and the therapeutic product is aryl hydrocarbon receptor interacting protein-like 1 (AIPL1);

[0628] (15) the ocular condition is associated with Leber congenital amaurosis 7 (LCA 7), and the therapeutic product is cone-rod homeobox (CRX);

[0629] (16) the ocular condition is associated with Leber congenital amaurosis 8 (LCA 8), and the therapeutic product is Crumbs cell polarity complex component 1 (CRB1);

[0630] (17) the ocular condition is associated with Leber congenital amaurosis 9 (LCA 9), and the therapeutic product is nicotinamide nucleotide adenylyltransferase 1 (NMNAT1);

[0631] (18) the ocular condition is associated with Leber congenital amaurosis 10 (LCA 10), and the therapeutic product is centrosomal protein 290 (CEP290);

[0632] (19) the ocular condition is associated with Leber congenital amaurosis 11 (LCA 11), and the therapeutic product is inosine monophosphate dehydrogenase 1 (IMPDH1);

[0633] (20) the ocular condition is associated with Leber congenital amaurosis 15 (LCA 15), and the therapeutic product is tubby-like protein 1 (TULP1);

[0634] (21) the ocular condition is associated with LHON, and the therapeutic product is mitochondrially encoded NADH dehydrogenase 4 (MT-ND4);

[0635] (22) the ocular condition is associated with LHON, and the therapeutic product is mitochondrially encoded NADH dehydrogenase 6 (MT-ND6);

[0636] (23) the ocular condition is associated with choroideremia, and the therapeutic product is Rab escort protein 1 (CHM);

[0637] (24) the ocular condition is associated with X-linked retinoschisis (XLRS), and the therapeutic product is retinoschisin (RS1);

[0638] (25) the ocular condition is associated with Bardet-Biedl Syndrome 1, and the therapeutic product is Bardet-Biedl Syndrome 1 (BBS1);

[0639] (26) the ocular condition is associated with Bardet-Biedl Syndrome 6, and the therapeutic product is McKusick-Kaufman Syndrome (MKKS);

[0640] (27) the ocular condition is associated with Bardet-Biedl Syndrome 10, and the therapeutic product is Bardet-Biedl Syndrome 10 (BBS10);

[0641] (28) the ocular condition is associated with Cone Dystrophy, and the therapeutic product is Guanylate Cyclase Activator 1A (GUCA1A);

[0642] (29) the ocular condition is associated with Optic Atrophy, and the therapeutic product is OPA1 Mitochondrial Motor Protein-Like GTPase (OPA1);

[0643] (30) the ocular condition is associated with Retinitis Pigmentosa 1, and the therapeutic product is RP1 Axonal Microtubule-Associated (RP1);

[0644] (31) the ocular condition is associated with Retinitis Pigmentosa 2, and the therapeutic product is ARL3 GTPase-Activating Factor for RP2 (RP2);

[0645] (32) the ocular condition is associated with Retinitis Pigmentosa 7, and the therapeutic product is Peripherin 2 (PRPH2);

[0646] (33) the ocular condition is associated with Retinitis Pigmentosa 11, and the therapeutic product is Pre-mRNA Processing Factor 31 (PRPF31);

[0647] (34) the ocular condition is associated with Retinitis Pigmentosa 13, and the therapeutic product is Pre-mRNA Processing Factor 8 (PRPF8);

[0648] (35) the ocular condition is associated with Retinitis Pigmentosa 37, and the therapeutic product is Nuclear Receptor Subfamily 2, Group E, Member 3 (NR2E3);

[0649] (36) the ocular condition is associated with Retinitis Pigmentosa 38, and the therapeutic product is MER Proto-Oncogene Tyrosine Kinase (MERTK);

[0650] (37) the ocular condition is associated with Retinitis Pigmentosa 40, and the therapeutic product is Phosphodiesterase 6B (PDE6B);

[0651] (38) the ocular condition is associated with retinitis pigmentosa 41, and the therapeutic product is Prominin 1 (PROM1);

[0652] (39) the ocular condition is associated with retinitis pigmentosa 56, and the therapeutic product is interphotoreceptor matrix protein 2 (IMPG2);

[0653] (40) the ocular condition is associated with retinitis pigmentosa 62, and the therapeutic product is male germ cell associated kinase (MAK);

[0654] (41) the ocular condition is associated with retinitis pigmentosa 80, and the therapeutic product is intraflagellar transport 140 (IFT140); or

[0655] (42) the ocular condition is associated with Best disease, and the therapeutic product is Bestrophin 1 (BEST1).

[0656] 31. The method of any one of paragraphs 1-11 and 15-18, wherein:

[0657] (1) the ocular condition is associated with X-linked retinitis pigmentosa (XLRP), and the therapeutic product is retinitis pigmentosa GTPase regulator (RPGR);

[0658] (2) the ocular condition is associated with achromatopsia, and the therapeutic product is cyclic nucleotide-gated channel beta 3 (CNGB3); or

[0659] (3) the ocular condition is associated with achromatopsia, and the therapeutic product is cyclic nucleotide-gated channel alpha 3 (CNGA3).

[0660] 32. The method of any one of paragraphs 1-31, wherein the recombinant viral vector further comprises a nucleotide sequence encoding a promoter or an enhancer-promoter operably linked to the nucleotide sequence encoding the therapeutic product, and wherein the promoter or enhancer-promoter is:

[0661] (1) a CAG promoter;

[0662] (2) a CBA promoter;

[0663] (3) a CMV promoter;

[0664] (4) a PR1.7 promoter;

[0665] (5) a rhodopsin kinase (GRK1) photoreceptor-specific enhancer-promoter.

[0666] (6) hCARp promoter;

[0667] (7) hRKp;

[0668] (8) cone photoreceptor-specific human arrestin 3 (ARR3) promoter;

[0669] (9) rhodopsin promoter; or

[0670] (10) U6 promoter.

[0671] 33. The method of any of paragraphs 1-11 and 13-15, wherein the recombinant viral vector further comprises a nucleotide sequence encoding a cone-specific promoter operably linked to the nucleotide sequence encoding the therapeutic product, and wherein:

[0672] (1) the eye condition is associated with red-green color blindness and the therapeutic product is L opsin (OPN1LW);

[0673] (2) the eye condition is associated with red-green color blindness and the therapeutic product is M opsin (OPN1MW);

[0674] (3) the eye condition is associated with blue cone monochromacy and the therapeutic product is M opsin (OPN1MW);

[0675] (4) the eye condition is associated with cone dystrophy and the therapeutic product is Guanylate cyclase activator 1A (GUCA1A); or

[0676] (5) the eye condition is associated with blue cone monochromacy (BCM) and the therapeutic product is L opsin (OPN1LW).

[0677] 34. The method of any of paragraphs 1-33, wherein the administering step delivers a therapeutically effective amount of the therapeutic product to the retina of the human subject.

[0678] 35. The method of paragraph 34, wherein the therapeutically effective amount of the therapeutic product is produced by a human retinal cell of the human subject.

[0679] 36. The method of paragraph 34, wherein the therapeutically effective amount of the therapeutic product is produced by a human photoreceptor cell, horizontal cell, bipolar cell, amacrine cell, retinal ganglion cell, and / or retinal pigment epithelial cell in the outer limiting membrane of the human subject.

[0680] 37. The method of paragraph 36, wherein the human photoreceptor cells are cone cells and / or rod cells.

[0681] 38. The method of paragraph 36, wherein the retinal ganglion cells are dwarf cells,

[0682] umbrella cells, double-plate cells, giant retinal ganglion cells, photosensitive ganglion cells, and / or Muller glial cells.

[0683] 39. The method of any one of paragraphs 1-38, wherein the recombinant viral vector is an rAAV vector.

[0684] 40. The method of paragraph 39, wherein the recombinant viral vector is an rAAV8 vector.

[0685] 41. The method of any one of paragraphs 1-40, further comprising, after the administering step, a step of monitoring the post-injection ocular heat profile of the injected material in the eye using an infrared thermal imager.

[0686] 42. The method of paragraph 41, wherein the infrared thermal imager is a FLIR T530 infrared thermal imager.

[0687] 43. The method of any one of paragraphs 1-43, wherein the recombinant nucleotide expression vector is administered at a dose of about 6.0 x 1010 10 genome copies per eye.

[0688] 44. The method of any one of paragraphs 1-43, wherein the recombinant nucleotide expression vector is administered at a dose of about 1.6 x 1010 11 genome copies per eye.

[0689] 45. The method of any one of paragraphs 1-43, wherein the recombinant nucleotide expression vector is administered at a dose of about 2.5 x 1010 11 genome copies per eye.

[0690] 46. The method of any one of paragraphs 1-43, wherein the recombinant nucleotide expression vector is administered at a dose of about 5.0 x 1010 11 genome copies per eye.

[0691] 47. The method of any one of paragraphs 1-43, wherein the recombinant nucleotide expression vector is administered at a dose of about 3.0 x 1010 12 genome copies per eye.

[0692] The present application provides the following:

[0693] 1. A method of subretinal administration for treating an ocular condition without vitrectomy, comprising administering to the subretinal space in the eye of a human subject in need of treatment a recombinant viral vector comprising a nucleotide sequence encoding a therapeutic product, such that the therapeutic product is expressed and the ocular condition is treated, wherein the method does not include performing a vitrectomy on the eye of the human patient.

[0694] 2. The method of item 1, wherein the administering step comprises administering the recombinant viral vector therapeutic product to the subretinal space of the eye of the human subject via the suprachoroidal space of the eye of the human subject.

[0695] 3. The method of item 2, wherein the administering step is by using a subretinal drug delivery device comprising a catheter that can be inserted through and toward the posterior pole of the suprachoroidal space, a small needle at the posterior pole for injection into the subretinal space.

[0696] 4. The method of item 3, wherein the administering step comprises inserting the catheter of the subretinal drug delivery device through the suprachoroidal space.

[0697] 5. A method of suprachoroidal administration for treating an ocular condition, comprising administering to the suprachoroidal space of the eye of a human subject in need of treatment a recombinant viral vector comprising a nucleotide sequence encoding a therapeutic product, such that the therapeutic product is expressed and the ocular condition is treated.

[0698] 6. The method of item 5, wherein the administering step is by using a suprachoroidal drug delivery device to inject the recombinant viral vector into the suprachoroidal space.

[0699] 7. The method of item 5 or 6, wherein the suprachoroidal drug delivery device is a microinjector.

[0700] 8. A method of juxtascleral administration for treating an ocular condition, comprising administering to the juxtascleral surface of the eye of a human subject in need of treatment a recombinant viral vector comprising a nucleotide sequence encoding a therapeutic product, such that the therapeutic product is expressed and the ocular condition is treated.

[0701] 9. The method of item 8, wherein the administering step is by using a juxtascleral drug delivery device comprising a cannula with a tip that can be inserted and held in direct apposition to the surface of the sclera.

[0702] 10. The method of item 9, wherein the administering step comprises inserting the tip of the cannula and holding it in direct apposition to the surface of the sclera.

[0703] 11. The method of any of items 1 to 10, wherein the therapeutic product is not an anti-human vascular endothelial growth factor (hVEGF) antibody.

[0704] 12. The method of any of items 1 to 11, wherein the ocular condition is not associated with neovascular age-related macular degeneration (nAMD).

[0705] 13. A method of subretinal administration for treating an ocular condition concomitant with vitrectomy, comprising administering to the subretinal space in the eye of a human subject in need of treatment a recombinant viral vector comprising a nucleotide sequence encoding a therapeutic product, such that the therapeutic product is expressed and the ocular condition is treated, wherein the method comprises performing vitrectomy on the eye of the human patient, and wherein the therapeutic product is not an anti-human vascular endothelial growth factor (hVEGF) antibody.

[0706] 14. The method of item 13, wherein the vitrectomy is a partial vitrectomy.

[0707] 15. A method of subretinal administration for treating an ocular condition, comprising administering to the subretinal space of the posterior of the eye of a human subject in need of treatment a recombinant viral vector comprising a nucleotide sequence encoding a therapeutic product, such that the therapeutic product is expressed and the ocular condition is treated, wherein the method does not comprise performing vitrectomy on the eye of the human patient.

[0708] 16. The method of item 15, wherein the administering step is by intravitreal injection.

[0709] 17. The method of item 16, wherein the intravitreal injection comprises inserting a sharp needle into the sclera via the superior or inferior side of the eye and passing the sharp needle completely through the vitreous body to inject the recombinant viral vector into the subretinal space on the other side.

[0710] 18. The method of item 16, wherein the intravitreal injection comprises inserting a trocar into the sclera and inserting a cannula through the trocar and through the vitreous body to inject the recombinant viral vector into the subretinal space on the other side.

[0711] 19. The method of any of items 15 to 18, wherein the therapeutic product is an anti-hVEGF antibody.

[0712] 20. The method of item 19, wherein the anti-hVEGF antibody is an anti-hVEGF antigen-binding fragment.

[0713] 21. The method of item 20, wherein the anti-hVEGF antigen-binding fragment is a Fab, F(ab')2, or single-chain variable fragment (scFv).

[0714] 22. The method of any one of items 19-21, wherein the anti-hVEGF antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 2 or SEQ ID NO: 4 and a light chain comprising the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 3.

[0715] 23. The method of any one of items 19-21, wherein the anti-hVEGF antibody comprises light chain CDRs 1-3 of SEQ ID NOs: 14-16 and heavy chain CDRs 1-3 of SEQ ID NOs: 17-19 or SEQ ID NOs: 20, 18, and 21.

[0716] 24. The method of any one of items 19-23, wherein the ocular condition is associated with nAMD, dry age-related macular degeneration (dry AMD), retinal vein occlusion (RVO), diabetic macular edema (DME), or diabetic retinopathy (DR).

[0717] 25. The method of any one of items 19-23, wherein the ocular condition is associated with nAMD.

[0718] 26. The method of any one of items 1-11 and 13-18, wherein:

[0719] (1) the ocular condition is associated with Batten-CLN1 and the therapeutic product is palmitoyl-protein thioesterase 1 (PPT1);

[0720] (2) the ocular condition is associated with Batten-CLN2 and the therapeutic product is tripeptidyl-peptidase 1 (TPPl);

[0721] (3) the ocular condition is associated with Batten-CLN3 and the therapeutic product is Battenin (CLN3);

[0722] (4) the ocular condition is associated with Batten-CLN6 and the therapeutic product is CLN6 transmembrane ER protein (CLN6);

[0723] (5) the ocular condition is associated with Batten-CLN7 and the therapeutic product is major facilitator superfamily domain containing 8 (MFSD8);

[0724] (6) the ocular condition is associated with Usher’s-Type 1 and the therapeutic product is myosin VIIA (MY07A);

[0725] (7) the ocular condition is associated with Usher’s-Type 1 and the therapeutic product is cadherin-related 23 (CDH23);

[0726] (8) the ocular condition is associated with Usher’s-Type 2 and the therapeutic product is protocadherin-related 15 (PCDH15);

[0727] (9) the ocular condition is associated with Usher’s-Type 2 and the therapeutic product is Usherin (USH2A);

[0728] (10) the ocular condition is associated with Usher’s-Type 3 and the therapeutic product is Clarin 1 (CLRN1);

[0729] (11) the ocular condition is associated with Stargardt’s and the therapeutic product is ATP-binding cassette subfamily A member 4 (ABCA4);

[0730] (12) the ocular condition is associated with Stargardt’s and the therapeutic product is ELOVL fatty acid elongase 4 (ELOVL4);

[0731] (13) the ocular condition is associated with uveitis and the therapeutic product is an anti- interleukin 6 (IL6) monoclonal antibody;

[0732] (14) the ocular condition is associated with uveitis and the therapeutic product is an anti-TNF-a (TNF) monoclonal antibody;

[0733] (15) the ocular condition is associated with diabetic macular edema (DME) and the therapeutic product is an anti-IL6 monoclonal antibody;

[0734] (16) the ocular condition is associated with red-green color blindness and the therapeutic product is L opsin (OPN1LW);

[0735] (17) the ocular condition is associated with red-green color blindness and the therapeutic product is M opsin (OPN1MW);

[0736] (18) the ocular condition is associated with blue cone monochromacy and the therapeutic product is M opsin (OPN1MW);

[0737] (19) the ocular condition is associated with Leber congenital amaurosis 1 (LCA 1), and the therapeutic product is retinal guanylate cyclase 2D (GUCY2D);

[0738] (20) the ocular condition is associated with Leber congenital amaurosis 2 (LCA 2), and the therapeutic product is retinal isomerohydrolase RPE65 (RPE65);

[0739] (21) the ocular condition is associated with LCA 3, and the therapeutic product is Spermatogenesis associated 7 (SPATA7);

[0740] (22) the ocular condition is associated with Leber congenital amaurosis 4 (LCA 4), and the therapeutic product is Aryl hydrocarbon receptor interacting protein like 1 (AIPL1);

[0741] (23) the ocular condition is associated with Leber congenital amaurosis 5 (LCA 5), and the therapeutic product is Lebercilin (LCA5);

[0742] (24) the ocular condition is associated with Leber congenital amaurosis 6 (LCA 6), and the therapeutic product is RPGR interacting protein 1 (RPGRIP1);

[0743] (25) the ocular condition is associated with Leber congenital amaurosis 7 (LCA 7), and the therapeutic product is Cone-rod homeobox (CRX);

[0744] (26) the ocular condition is associated with Leber congenital amaurosis 8 (LCA 8), and the therapeutic product is Crumbs cell polarity complex component 1 (CRB1);

[0745] (27) the ocular condition is associated with Leber congenital amaurosis 9 (LCA 9), and the therapeutic product is Nicotinamide nucleotide adenylyltransferase 1 (NMNAT1);

[0746] (28) the ocular condition is associated with Leber congenital amaurosis 10 (LCA 10), and the therapeutic product is Centrosomal protein 290 (CEP290);

[0747] (29) the ocular condition is associated with Leber congenital amaurosis 11 (LCA 11), and the therapeutic product is Inosine monophosphate dehydrogenase 1 (IMPDH1);

[0748] (30) the ocular condition is associated with Leber congenital amaurosis 12 (LCA 12), and the therapeutic product is retinal degeneration 3, GUCY2D regulator (RD3);

[0749] (31) the ocular condition is associated with Leber congenital amaurosis 13 (LCA 13), and the therapeutic product is retinol dehydrogenase 12 (RDH12);

[0750] (32) the ocular condition is associated with Leber congenital amaurosis 14 (LCA 14), and the therapeutic product is lecithin retinol acyltransferase (LRAT);

[0751] (33) the ocular condition is associated with Leber congenital amaurosis 15 (LCA 15), and the therapeutic product is tubby-like protein 1 (TULP1);

[0752] (34) the ocular condition is associated with Leber congenital amaurosis 16 (LCA 16), and the therapeutic product is potassium voltage-gated channel subfamily J member 13 (KCNJ13);

[0753] (35) the ocular condition is associated with Leber’s hereditary optic neuropathy (LHON), and the therapeutic product is mitochondrial encoded NADH dehydrogenase 1 (MT-ND1);

[0754] (36) the ocular condition is associated with LHON, and the therapeutic product is mitochondrial encoded NADH dehydrogenase 4 (MT-ND4);

[0755] (37) the ocular condition is associated with LHON, and the therapeutic product is mitochondrial encoded NADH dehydrogenase 6 (MT-ND6);

[0756] (38) the ocular condition is associated with neuromyelitis optica (NMO), and the therapeutic product is an anti-complement C5 monoclonal antibody;

[0757] (39) the ocular condition is associated with NMO, and the therapeutic product is an anti-IL6 monoclonal antibody;

[0758] (40) the ocular condition is associated with uveitis, and the therapeutic product is an anti-complement C5 monoclonal antibody;

[0759] (41) the ocular condition is associated with uveitis, and the therapeutic product is angiotensin I converting enzyme (ACE);

[0760] (42) the ocular condition is associated with uveitis, and the therapeutic product is interleukin 10 (IL10);

[0761] (43) the ocular condition is associated with uveitis, and the therapeutic product is an anti-TNF monoclonal antibody;

[0762] (44) the ocular condition is associated with choroideremia, and the therapeutic product is Rab Escort Protein 1 (CHM);

[0763] (45) the ocular condition is associated with X-linked retinoschisis (XLRS), and the therapeutic product is retinoschisin (RS1);

[0764] (46) the ocular condition is associated with Bardet-Biedl syndrome 1, and the therapeutic product is Bardet-Biedl syndrome 1 (BBS1);

[0765] (47) the ocular condition is associated with Bardet-Biedl syndrome 2, and the therapeutic product is Bardet-Biedl syndrome 2 (BBS2);

[0766] (48) the ocular condition is associated with Bardet-Biedl syndrome 3, and the therapeutic product is ADP Ribosylation Factor Like GTPase 6 (ARL6);

[0767] (49) the ocular condition is associated with Bardet-Biedl syndrome 4, and the therapeutic product is Bardet-Biedl syndrome 4 (BBS4);

[0768] (50) the ocular condition is associated with Bardet-Biedl syndrome 5, and the therapeutic product is Bardet-Biedl syndrome 5 (BBS5);

[0769] (51) the ocular condition is associated with Bardet-Biedl syndrome 6, and the therapeutic product is McKusick-Kaufman Syndrome (MKKS);

[0770] (52) the ocular condition is associated with Bardet-Biedl syndrome 7, and the therapeutic product is Bardet-Biedl syndrome 7 (BBS7);

[0771] (53) the ocular condition is associated with Bardet-Biedl syndrome 8, and the therapeutic product is Tetratricopeptide Repeat Domain 8 (TTC8);

[0772] (54) the ocular condition is associated with Bardet-Biedl syndrome 9, and the therapeutic product is Bardet-Biedl syndrome 9 (BBS9);

[0773] (55) the ocular condition is associated with Bardet-Biedl Syndrome 10, and the therapeutic product is Bardet-Biedl Syndrome 10 (BBS10);

[0774] (56) the ocular condition is associated with Bardet-Biedl Syndrome 11, and the therapeutic product is Tripartite motif containing 32 (TRIM32);

[0775] (57) the ocular condition is associated with Bardet-Biedl Syndrome 12, and the therapeutic product is Bardet-Biedl Syndrome 12 (BBS12);

[0776] (58) the ocular condition is associated with Bardet-Biedl Syndrome 13, and the therapeutic product is MKS transition zone complex subunit 1 (MKS1);

[0777] (59) the ocular condition is associated with Bardet-Biedl Syndrome 14, and the therapeutic product is Centrosomal Protein 290 (CEP290);

[0778] (60) the ocular condition is associated with Bardet-Biedl Syndrome 15, and the therapeutic product is WD Repeat Containing Planar Cell Polarity Effector (WDPCP);

[0779] (61) the ocular condition is associated with Bardet-Biedl Syndrome 16, and the therapeutic product is Serologically Defined Colon Cancer Antigen 8 (SDCCAG8);

[0780] (62) the ocular condition is associated with Bardet-Biedl Syndrome 17, and the therapeutic product is Leucine Zipper Transcriptional Regulator Like 1 (LZTFL1);

[0781] (63) the ocular condition is associated with Bardet-Biedl Syndrome 18, and the therapeutic product is BBSome Interacting Protein 1 (BBIP1);

[0782] (64) the ocular condition is associated with Bardet-Biedl Syndrome 19, and the therapeutic product is Intraflagellar Transport Protein 27 (IFT27);

[0783] (65) the ocular condition is associated with Cone Dystrophy, and the therapeutic product is Guanylate Cyclase Activator 1A (GUCA1A);

[0784] (66) the ocular condition is associated with Optic Nerve Atrophy, and the therapeutic product is OPA1 Mitochondrial Motor Protein Like GTPase (OPA1);

[0785] (67) the ocular condition is associated with retinitis pigmentosa 1 and the therapeutic product is RP1 axonal microtubule-associated (RP1);

[0786] (68) the ocular condition is associated with retinitis pigmentosa 2 and the therapeutic product is RP2 activator of ARL3 GTPase (RP2);

[0787] (69) the ocular condition is associated with retinitis pigmentosa 7 and the therapeutic product is peripherin 2 (PRPH2);

[0788] (70) the ocular condition is associated with retinitis pigmentosa 11 and the therapeutic product is pre-mRNA processing factor 31 (PRPF31);

[0789] (71) the ocular condition is associated with retinitis pigmentosa 12 and the therapeutic product is Crumbs cell polarity complex component 1 (CRB1);

[0790] (72) the ocular condition is associated with retinitis pigmentosa 13 and the therapeutic product is pre-mRNA processing factor 8 (PRPF8);

[0791] (73) the ocular condition is associated with retinitis pigmentosa 25 and the therapeutic product is ocular albinism homolog (EYS);

[0792] (74) the ocular condition is associated with retinitis pigmentosa 28 and the therapeutic product is FAM161 centrosomal protein A (FAM161A);

[0793] (75) the ocular condition is associated with retinitis pigmentosa 37 and the therapeutic product is nuclear receptor subfamily 2, group E, member 3 (NR2E3);

[0794] (76) the ocular condition is associated with retinitis pigmentosa 38 and the therapeutic product is MER proto-oncogene tyrosine kinase (MERTK);

[0795] (77) the ocular condition is associated with retinitis pigmentosa 40 and the therapeutic product is phosphodiesterase 6B (PDE6B);

[0796] (78) the ocular condition is associated with retinitis pigmentosa 41 and the therapeutic product is Prominin 1 (PROM1);

[0797] (79) the ocular condition is associated with retinitis pigmentosa 43 and the therapeutic product is phosphodiesterase 6A (PDE6A);

[0798] (80) the ocular pathology is associated with retinitis pigmentosa 56, and the therapeutic product is interphotoreceptor matrix protein 2 (IMPG2);

[0799] (81) the ocular pathology is associated with retinitis pigmentosa 62, and the therapeutic product is male germ cell associated kinase (MAK);

[0800] (82) the ocular pathology is associated with retinitis pigmentosa 80, and the therapeutic product is intraflagellar transport 140 (IFT140);

[0801] (83) the ocular pathology is associated with dry AMD, and the therapeutic product is an anti-complement C5 monoclonal antibody;

[0802] (84) the ocular pathology is associated with dry AMD, and the therapeutic product is an anti-membrane attack complex (MAC) monoclonal antibody;

[0803] (85) the ocular pathology is associated with dry AMD, and the therapeutic product is HtrA serine peptidase 1 (HTRA1);

[0804] (86) the ocular pathology is associated with Best disease, and the therapeutic product is bestrophin 1 (BEST1);

[0805] (87) the ocular pathology is associated with dry AMD, and the therapeutic product is a complement factor B antisense oligonucleotide;

[0806] (88) the ocular pathology is associated with dry AMD, and the therapeutic product is an anti-beta-amyloid monoclonal antibody;

[0807] (89) the ocular pathology is associated with dry AMD, and the therapeutic product is CD59 glycoprotein (CD59);

[0808] (90) the ocular pathology is associated with dry AMD, and the therapeutic product is channelrhodopsin-1 (ChR1);

[0809] (91) the ocular pathology is associated with dry AMD, and the therapeutic product is channelrhodopsin-2 (ChR2), a light-sensitive protein found in Chlamydomonas reinhardtii;

[0810] (92) the ocular pathology is associated with dry AMD, and the therapeutic product is an anti-complement factor C5a aptamer;

[0811] (93) the ocular pathology is associated with dry AMD, and the therapeutic product is an anti-complement factor D monoclonal antibody;

[0812] (94) the ocular condition is associated with age-related retinal ganglion cell (RGC) degeneration, and the therapeutic product is DnaJ heat shock protein family (Hsp40) member C3 (DNAJC3);

[0813] (95) the ocular condition is associated with blue cone monochromacy (BCM), and the therapeutic product is L opsin (OPN1MW);

[0814] (96) the ocular condition is associated with glaucoma, and the therapeutic product is beta-2 adrenergic receptor siRNA;

[0815] (97) the ocular condition is associated with glaucoma, and the therapeutic product is caspase-2 (CASP2);

[0816] (98) the ocular condition is associated with glaucoma, and the therapeutic product is insulin receptor substrate 1 (IRS1);

[0817] (99) the ocular condition is associated with glaucoma, and the therapeutic product is HIF-1 responsive protein RTP801 (RTP801);

[0818] (100) the ocular condition is associated with glaucoma, and the therapeutic product is transforming growth factor beta 2 (TGFB2);

[0819] (101) the ocular condition is associated with glaucoma, and the therapeutic product is brain-derived neurotrophic factor (BDNF);

[0820] (102) the ocular condition is associated with glaucoma, and the therapeutic product is ciliary neurotrophic factor (CNTF);

[0821] (103) the ocular condition is associated with glaucoma, and the therapeutic product is prostaglandin endoperoxide synthase 2 (PTGS2);

[0822] (104) the ocular condition is associated with glaucoma, and the therapeutic product is prostaglandin F receptor (PTGFR);

[0823] (105) the ocular condition is associated with glaucoma, and the therapeutic product is hyaluronidase;

[0824] (106) the ocular condition is associated with glaucoma, and the therapeutic product is pigment epithelium-derived factor (PEDF);

[0825] (107) the ocular condition is associated with glaucoma and the therapeutic product is vascular endothelial growth factor (VEGF);

[0826] (108) the ocular condition is associated with glaucoma and the therapeutic product is placental growth factor (PGF);

[0827] (109) the ocular condition is associated with glaucoma and the therapeutic product is myocilin (MYOC);

[0828] (110) the ocular condition is associated with NMO and the therapeutic product is anti-complement C5 monoclonal antibody;

[0829] (111) the ocular condition is associated with NMO and the therapeutic product is C-C motif chemokine receptor 5 (CCR5) siRNA;

[0830] (112) the ocular condition is associated with NMO and the therapeutic product is anti-CD19 monoclonal antibody;

[0831] (113) the ocular condition is associated with retinitis pigmentosa associated with rhodopsin mutations and the therapeutic product is channelrhodopsin-1 (ChRl);

[0832] (114) the ocular condition is associated with retinitis pigmentosa associated with rhodopsin mutations and the therapeutic product is channelrhodopsin-2 (ChR2);

[0833] (115) the ocular condition is associated with retinitis pigmentosa and the therapeutic product is ciliary neurotrophic factor (CNTF);

[0834] (116) the ocular condition is associated with autosomal recessive retinitis pigmentosa and the therapeutic product is Crumbs cell polarity complex component 1 (CRBl);

[0835] (117) the ocular condition is associated with autosomal recessive retinitis pigmentosa and the therapeutic product is Crumbs cell polarity complex component 2 (CRB2);

[0836] (118) the ocular condition is associated with retinitis pigmentosa and the therapeutic product is histone deacetylase 4 (HDAC4);

[0837] (119) the ocular condition is associated with retinitis pigmentosa and the therapeutic product is rhodopsin (RHO);

[0838] (120) the ocular condition is associated with retinitis pigmentosa, and the therapeutic product is nerve growth factor (NGF);

[0839] (121) the ocular condition is associated with retinitis pigmentosa, and the therapeutic product is nuclear factor, erythroid 2-like 2 (NRF2);

[0840] (122) the ocular condition is associated with retinitis pigmentosa, and the therapeutic product is pigment epithelium-derived factor (PEDF);

[0841] (123) the ocular condition is associated with retinitis pigmentosa, and the therapeutic product is glutathione S-transferase PI 1 (GSTP1);

[0842] (124) the ocular condition is associated with retinitis pigmentosa, and the therapeutic product is rod-derived cone viability factor (RDCVF);

[0843] (125) the ocular condition is associated with retinitis pigmentosa, and the therapeutic product is rhodopsin (RHO);

[0844] (126) the ocular condition is associated with retinitis pigmentosa, and the therapeutic product is retinaldehyde binding protein 1 (RLBP1);

[0845] (127) the ocular condition is associated with Stargardt disease, and the therapeutic product is an anti-complement C5 aptamer;

[0846] (128) the ocular condition is associated with uveitis, and the therapeutic product is double homeobox 4 (DUX4);

[0847] (129) the ocular condition is associated with uveitis, and the therapeutic product is NLR family, pyrin domain containing 3 (NLRP3);

[0848] (130) the ocular condition is associated with uveitis, and the therapeutic product is spleen tyrosine kinase (SYK);

[0849] (131) the ocular condition is associated with uveitis, and the therapeutic product is adrenocorticotropic hormone (ACTH);

[0850] (132) the ocular condition is associated with uveitis, and the therapeutic product is caspase 1 (CASP1);

[0851] (133) the ocular condition is associated with uveitis, and the therapeutic product is an anti-CD59 monoclonal antibody;

[0852] (134) the ocular condition is associated with uveitis, and the therapeutic product is an anti-complement C5 aptamer;

[0853] (135) the ocular condition is associated with corneal neovascularization, and the therapeutic product is Insulin Receptor Substrate 1 (IRS1);

[0854] (136) the ocular condition is associated with corneal neovascularization, and the therapeutic product is NOTCH Regulated Ankyrin Repeat Protein (NRARP);

[0855] (137) the ocular condition is associated with diabetic retinopathy, and the therapeutic product is NOTCH Regulated Ankyrin Repeat Protein (NRARP);

[0856] (138) the ocular condition is associated with diabetic retinopathy, and the therapeutic product is alpha-2-antiplasmin (A2AP);

[0857] (139) the ocular condition is associated with diabetic retinopathy, and the therapeutic product is plasminogen (PLG);

[0858] (140) the ocular condition is associated with diabetic retinopathy, and the therapeutic product is growth hormone;

[0859] (141) the ocular condition is associated with diabetic retinopathy, and the therapeutic product is insulin-like growth factor 1 (IGF1);

[0860] (142) the ocular condition is associated with diabetic retinopathy, and the therapeutic product is interleukin 1 beta (IL1B);

[0861] (143) the ocular condition is associated with diabetic retinopathy, and the therapeutic product is angiotensin I converting enzyme 2 (ACE2);

[0862] (144) the ocular condition is associated with diabetic retinopathy, and the therapeutic product is IRS1;

[0863] (145) the ocular condition is associated with diabetic retinopathy, and the therapeutic product is an anti-integrin oligopeptide;

[0864] (146) the ocular condition is associated with diabetic retinopathy, and the therapeutic product is an anti-placental growth factor (PGF) monoclonal antibody;

[0865] (147) the ocular condition is associated with Graves Ophthalmopathy, and the therapeutic product is an anti-CD40 monoclonal antibody;

[0866] (148) the ocular condition is associated with Graves Ophthalmopathy, and the therapeutic product is an anti-insulin-like growth factor 1 receptor (IGF1R) monoclonal antibody;

[0867] (149) the ocular condition is associated with Graves Ophthalmopathy, and the therapeutic product is an anti-insulin-like growth factor 2 receptor (IGF2R) monoclonal antibody;

[0868] (150) the ocular condition is associated with DME, and the therapeutic product is an anti-integrin oligopeptide;

[0869] (151) the ocular condition is associated with DME, and the therapeutic product is an anti-placental growth factor (PGF) monoclonal antibody;

[0870] (152) the ocular condition is associated with DME, and the therapeutic product is an RTP801 siRNA;

[0871] (153) the ocular condition is associated with vision loss associated with multiple sclerosis (MS), and the therapeutic product is ND1;

[0872] (154) the ocular condition is associated with myopia, and the therapeutic product is matrix metalloproteinase 2 (MMP2) RNAi;

[0873] (155) the ocular condition is associated with X-linked recessive ocular albinism, and the therapeutic product is G protein-coupled receptor 143 (GPR143);

[0874] (156) the ocular condition is associated with ocular albinism type 1, and the therapeutic product is tyrosinase (TYR);

[0875] (157) the ocular condition is associated with optic neuritis, and the therapeutic product is caspase 2 (CASP2);

[0876] (158) the ocular condition is associated with optic neuritis, and the therapeutic product is an anti-leucine-rich repeat and Ig domain-containing protein 1 (LINGO1) monoclonal antibody; or

[0877] (159) the ocular condition is associated with polypoidal choroidal vasculopathy, and the therapeutic product is an anti-complement C5 aptamer.

[0878] 27. The method of any of items 1 to 11 and 15 to 18, wherein: (1) the ocular condition is associated with X-linked retinitis pigmentosa (XLRP), and the therapeutic product is retinitis pigmentosa GTPase regulator (RPGR).

[0879] (2) the ocular condition is associated with achromatopsia (ACHM), and the therapeutic product is cyclic nucleotide-gated channel beta 3 (CNGB3);

[0880] (3) the ocular condition is associated with achromatopsia, and the therapeutic product is cyclic nucleotide-gated channel alpha 3 (CNGA3); or

[0881] (4) the ocular condition is associated with retinal dystrophy associated with bi-allelic RPE65 mutations, and the therapeutic product is retinoid isomerohydrolase RPE65 (RPE65).

[0882] 28. The method of any one of items 1 to 11 and 13 to 18, wherein:

[0883] (1) the ocular condition is associated with Batten-CLN1, and the therapeutic product is palmitoyl-protein thioesterase 1 (PPT1);

[0884] (2) the ocular condition is associated with Batten-CLN2, and the therapeutic product is tripeptidyl-peptidase 1 (TPPl);

[0885] (3) the ocular condition is associated with Batten-CLN3, and the therapeutic product is Battenin (CLN3);

[0886] (4) the ocular condition is associated with uveitis, and the therapeutic product is an anti- interleukin 6 (IL6) monoclonal antibody;

[0887] (5) the ocular condition is associated with uveitis, and the therapeutic product is an anti-TNF-alpha (TNF) monoclonal antibody;

[0888] (6) the ocular condition is associated with diabetic macular edema (DME), and the therapeutic product is an anti-IL6 monoclonal antibody;

[0889] (7) the ocular condition is associated with red-green color blindness, and the therapeutic product is L opsin (OPN1LW);

[0890] (8) the ocular condition is associated with red-green color blindness, and the therapeutic product is M opsin (OPN1MW);

[0891] (9) the ocular condition is associated with blue cone monochromacy, and the therapeutic product is M opsin (OPN1MW);

[0892] (10) the ocular condition is associated with Leber congenital amaurosis 1 (LCA 1), and the therapeutic product is retinal guanylate cyclase 2D (GUCY2D);

[0893] (11) the ocular condition is associated with Leber congenital amaurosis 2 (LCA 2), and the therapeutic product is retinal isomerohydrolase RPE65 (RPE65);

[0894] (12) the ocular condition is associated with Leber congenital amaurosis 7 (LCA 7), and the therapeutic product is cone-rod homeobox (CRX);

[0895] (13) the ocular condition is associated with Leber congenital amaurosis 11 (LCA 11), and the therapeutic product is inosine monophosphate dehydrogenase 1 (IMPDH1);

[0896] (14) the ocular condition is associated with Leber congenital amaurosis 12 (LCA 12), and the therapeutic product is retinal degeneration 3, GUCY2D regulator (RD3);

[0897] (15) the ocular condition is associated with Leber congenital amaurosis 13 (LCA 13), and the therapeutic product is retinol dehydrogenase 12 (RDH12);

[0898] (16) the ocular condition is associated with Leber congenital amaurosis 15 (LCA 15), and the therapeutic product is tubby-like protein 1 (TULP1);

[0899] (17) the ocular condition is associated with Leber congenital amaurosis 16 (LCA 16), and the therapeutic product is potassium voltage-gated channel subfamily J member 13 (KCNJ13);

[0900] (18) the ocular condition is associated with Leber’s hereditary optic neuropathy (LHON), and the therapeutic product is mitochondrially encoded NADH dehydrogenase 1 (MT-ND1);

[0901] (19) the ocular condition is associated with LHON, and the therapeutic product is mitochondrially encoded NADH dehydrogenase 4 (MT-ND4);

[0902] (20) the ocular condition is associated with LHON, and the therapeutic product is mitochondrially encoded NADH dehydrogenase 6 (MT-ND6);

[0903] (21) the ocular condition is associated with neuromyelitis optica (NMO), and the therapeutic product is an anti-complement C5 monoclonal antibody;

[0904] (22) the ocular condition is associated with NMO, and the therapeutic product is an anti-IL6 monoclonal antibody;

[0905] (23) the ocular condition is associated with uveitis, and the therapeutic product is an anti-complement C5 monoclonal antibody;

[0906] (24) the ocular condition is associated with uveitis, and the therapeutic product is angiotensin I converting enzyme (ACE);

[0907] (25) the ocular condition is associated with uveitis, and the therapeutic product is interleukin 10 (IL10);

[0908] (26) the ocular condition is associated with uveitis, and the therapeutic product is an anti-TNF monoclonal antibody;

[0909] (27) the ocular condition is associated with X-linked retinoschisis (XLRS), and the therapeutic product is retinoschisin (RS1);

[0910] (28) the ocular condition is associated with Bardet-Biedl syndrome 1, and the therapeutic product is Bardet-Biedl syndrome 1 (BBS1);

[0911] (29) the ocular condition is associated with Bardet-Biedl syndrome 3, and the therapeutic product is ADP ribosylation factor-like GTPase 6 (ARL6);

[0912] (30) the ocular condition is associated with Bardet-Biedl syndrome 5, and the therapeutic product is Bardet-Biedl syndrome 5 (BBS5);

[0913] (31) the ocular condition is associated with Bardet-Biedl syndrome 6, and the therapeutic product is McKusick-Kaufman syndrome (MKKS);

[0914] (32) the ocular condition is associated with Bardet-Biedl syndrome 10, and the therapeutic product is Bardet-Biedl syndrome 10 (BBS10);

[0915] (33) the ocular condition is associated with Bardet-Biedl syndrome 11, and the therapeutic product is tripartite motif containing 32 (TRIM32);

[0916] (34) the ocular condition is associated with Bardet-Biedl syndrome 13, and the therapeutic product is MKS transition zone complex subunit 1 (MKS1);

[0917] (35) the ocular condition is associated with Bardet-Biedl Syndrome 18, and the therapeutic product is BBSome interacting protein 1 (BBIP1);

[0918] (36) the ocular condition is associated with Bardet-Biedl Syndrome 19, and the therapeutic product is intraflagellar transport protein 27 (IFT27);

[0919] (37) the ocular condition is associated with cone dystrophy, and the therapeutic product is guanylate cyclase activator 1A (GUCA1A);

[0920] (38) the ocular condition is associated with retinitis pigmentosa 13, and the therapeutic product is pre-mRNA processing factor 8 (PRPF8);

[0921] (39) the ocular condition is associated with retinitis pigmentosa 37, and the therapeutic product is nuclear receptor subfamily 2, group E, member 3 (NR2E3); or

[0922] (40) the ocular condition is associated with Best disease, and the therapeutic product is bestrophin 1 (BEST1).

[0923] 29. The method of any one of items 1 to 11 and 15 to 18, wherein:

[0924] (1) the ocular condition is associated with retinal dystrophy associated with biallelic RPE65 mutations, and the therapeutic product is retinoid isomerohydrolase RPE65 (RPE65).

[0925] 30. The method of any one of items 1 to 11 and 13 to 18, wherein:

[0926] (1) the ocular condition is associated with Batten-CLN2, and the therapeutic product is tripeptidyl-peptidase 1 (TPPl);

[0927] (2) the ocular condition is associated with Usher Syndrome Type 1, and the therapeutic product is myosin VIIA (MY07A);

[0928] (3) the ocular condition is associated with Usher Syndrome Type 1, and the therapeutic product is cadherin-related 23 (CDH23);

[0929] (4) the ocular condition is associated with Usher Syndrome Type 2, and the therapeutic product is protocadherin-related 15 (PCDH15);

[0930] (5) the ocular condition is associated with Usher Syndrome Type 2, and the therapeutic product is Usherin (USH2A);

[0931] (6) the ocular condition is associated with Usher Syndrome Type 3, and the therapeutic product is Clarin 1 (CLRN1);

[0932] (7) the ocular condition is associated with Stargardt Disease, and the therapeutic product is ATP Binding Cassette Subfamily A Member 4 (ABCA4);

[0933] (8) the ocular condition is associated with Stargardt Disease, and the therapeutic product is ELOVL Fatty Acid Elongase 4 (ELOVL4);

[0934] (9) the ocular condition is associated with Red-Green Color Blindness, and the therapeutic product is L Opsin (OPN1LW);

[0935] (10) the ocular condition is associated with Red-Green Color Blindness, and the therapeutic product is M Opsin (OPN1MW);

[0936] (11) the ocular condition is associated with Blue Cone Monochromacy, and the therapeutic product is M Opsin (OPN1MW);

[0937] (12) the ocular condition is associated with Leber Congenital Amaurosis 1 (LCA 1), and the therapeutic product is Retinal Guanylate Cyclase 2D (GUCY2D);

[0938] (13) the ocular condition is associated with Leber Congenital Amaurosis 2 (LCA 2), and the therapeutic product is Retinal Isomerohydrolase RPE65 (RPE65);

[0939] (14) the ocular condition is associated with Leber Congenital Amaurosis 4 (LCA 4), and the therapeutic product is Aryl Hydrocarbon Receptor Interacting Protein Like 1 (AIPL1);

[0940] (15) the ocular condition is associated with Leber Congenital Amaurosis 7 (LCA 7), and the therapeutic product is Cone-Rod Homeobox (CRX);

[0941] (16) the ocular condition is associated with Leber Congenital Amaurosis 8 (LCA 8), and the therapeutic product is Crumbs Cell Polarity Complex Component 1 (CRB1);

[0942] (17) the ocular condition is associated with Leber Congenital Amaurosis 9 (LCA 9), and the therapeutic product is Nicotinamide Nucleotide Adenylyltransferase 1 (NMNAT1);

[0943] (18) the ocular condition is associated with Leber congenital amaurosis 10 (LCA 10), and the therapeutic product is centrosomal protein 290 (CEP290);

[0944] (19) the ocular condition is associated with Leber congenital amaurosis 11 (LCA 11), and the therapeutic product is inosine monophosphate dehydrogenase 1 (IMPDH1);

[0945] (20) the ocular condition is associated with Leber congenital amaurosis 15 (LCA 15), and the therapeutic product is tubby-like protein 1 (TULP1);

[0946] (21) the ocular condition is associated with LHON, and the therapeutic product is Mitochondrial encoded NADH dehydrogenase 4 (MT-ND4);

[0947] (22) the ocular condition is associated with LHON, and the therapeutic product is Mitochondrial encoded NADH dehydrogenase 6 (MT-ND6);

[0948] (23) the ocular condition is associated with choroideremia, and the therapeutic product is Rab escort protein 1 (CHM);

[0949] (24) the ocular condition is associated with X-linked retinoschisis (XLRS), and the therapeutic product is retinoschisin (RS1);

[0950] (25) the ocular condition is associated with Bardet-Biedl syndrome 1, and the therapeutic product is Bardet-Biedl syndrome 1 (BBS1);

[0951] (26) the ocular condition is associated with Bardet-Biedl syndrome 6, and the therapeutic product is McKusick-Kaufman syndrome (MKKS);

[0952] (27) the ocular condition is associated with Bardet-Biedl syndrome 10, and the therapeutic product is Bardet-Biedl syndrome 10 (BBS10);

[0953] (28) the ocular condition is associated with cone dystrophy, and the therapeutic product is guanylate cyclase activator 1A (GUCA1A);

[0954] (29) the ocular condition is associated with optic atrophy, and the therapeutic product is OPA1 mitochondrial motor protein-like GTPase (OPA1);

[0955] (30) the ocular condition is associated with retinitis pigmentosa 1 and the therapeutic product is RP1 axonal microtubule-associated (RP1);

[0956] (31) the ocular condition is associated with retinitis pigmentosa 2 and the therapeutic product is RP2 activator of ARL3 GTPase (RP2);

[0957] (32) the ocular condition is associated with retinitis pigmentosa 7 and the therapeutic product is peripherin 2 (PRPH2);

[0958] (33) the ocular condition is associated with retinitis pigmentosa 11 and the therapeutic product is pre-mRNA processing factor 31 (PRPF31);

[0959] (34) the ocular condition is associated with retinitis pigmentosa 13 and the therapeutic product is pre-mRNA processing factor 8 (PRPF8);

[0960] (35) the ocular condition is associated with retinitis pigmentosa 37 and the therapeutic product is nuclear receptor subfamily 2, group E, member 3 (NR2E3);

[0961] (36) the ocular condition is associated with retinitis pigmentosa 38 and the therapeutic product is MER proto-oncogene tyrosine kinase (MERTK);

[0962] (37) the ocular condition is associated with retinitis pigmentosa 40 and the therapeutic product is phosphodiesterase 6B (PDE6B);

[0963] (38) the ocular condition is associated with retinitis pigmentosa 41 and the therapeutic product is Prominin 1 (PROM1);

[0964] (39) the ocular condition is associated with retinitis pigmentosa 56 and the therapeutic product is interphotoreceptor matrix proteoglycan 2 (IMPG2);

[0965] (40) the ocular condition is associated with retinitis pigmentosa 62 and the therapeutic product is male germ cell associated kinase (MAK);

[0966] (41) the ocular condition is associated with retinitis pigmentosa 80 and the therapeutic product is intraflagellar transport protein 140 (IFT140); or

[0967] (42) the ocular condition is associated with Best disease and the therapeutic product is bestrophin 1 (BEST1).

[0968] 31. The method of any one of items 1 to 11 and 15 to 18, wherein:

[0969] (1) the ocular condition is associated with X-linked retinitis pigmentosa (XLRP), and the therapeutic product is retinitis pigmentosa GTPase regulator (RPGR);

[0970] (2) the ocular condition is associated with achromatopsia, and the therapeutic product is cyclic nucleotide-gated channel beta 3 (CNGB3); or

[0971] (3) the ocular condition is associated with achromatopsia, and the therapeutic product is cyclic nucleotide-gated channel alpha 3 (CNGA3).

[0972] 32. The method of any one of items 1 to 31, wherein the recombinant viral vector further comprises a nucleotide sequence encoding a promoter or enhancer-promoter operably linked to the nucleotide sequence encoding the therapeutic product, and wherein the promoter or enhancer-promoter is:

[0973] (1) a CAG promoter;

[0974] (2) a CBA promoter;

[0975] (3) a CMV promoter;

[0976] (4) a PR1.7 promoter;

[0977] (5) a rhodopsin kinase (GRK1) photoreceptor-specific enhancer-promoter;

[0978] (6) a hCARp promoter;

[0979] (7) a hRKp;

[0980] (8) a cone photoreceptor-specific human arrestin 3 (ARR3) promoter;

[0981] (9) a rhodopsin promoter; or

[0982] (10) a U6 promoter.

[0983] 33. The method of any one of items 1 to 11 and 13 to 15, wherein the recombinant viral vector further comprises a nucleotide sequence encoding a cone-specific promoter operably linked to the nucleotide sequence encoding the therapeutic product, and wherein:

[0984] (1) the eye condition is associated with red-green color blindness and the therapeutic product is L opsin (OPN1LW);

[0985] (2) the eye condition is associated with red-green color blindness and the therapeutic product is M opsin (OPN1MW);

[0986] (3) the eye condition is associated with blue cone monochromacy and the therapeutic product is M opsin (OPN1MW);

[0987] (4) the eye condition is associated with cone dystrophy and the therapeutic product is Guanylate Cyclase Activator 1A (GUCA1A); or

[0988] (5) the eye condition is associated with blue cone monochromacy (BCM) and the therapeutic product is L opsin (OPN1LW).

[0989] 34. The method of any one of clauses 1-33, wherein the administering step delivers a therapeutically effective amount of the therapeutic product to the retina of the human subject.

[0990] 35. The method of clause 34, wherein the therapeutically effective amount of the therapeutic product is produced by human retinal cells of the human subject.

[0991] 36. The method of clause 34, wherein the therapeutically effective amount of the therapeutic product is produced by human photoreceptor cells, horizontal cells, bipolar cells, amacrine cells, retinal ganglion cells, and / or retinal pigment epithelial cells in the outer limiting membrane of the human subject.

[0992] 37. The method of clause 36, wherein the human photoreceptor cells are cone cells and / or rod cells.

[0993] 38. The method of clause 36, wherein the retinal ganglion cells are dwarf cells, umbrella cells, biiayer cells, giant retinal ganglion cells, photosensitive ganglion cells, and / or Muller glial cells.

[0994] 39. The method of any one of clauses 1-38, wherein the recombinant viral vector is an rAAV vector.

[0995] 40. The method of clause 39, wherein the recombinant viral vector is an rAAV8 vector.

[0996] 41. The method of any one of clauses 1-40, further comprising a step, after the administering step, of monitoring post-injection thermal distribution of the injected material in the eye using an infrared thermographic camera.

[0997] 42. The method of item 41, wherein the infrared thermographic camera is a FLIR T530 infrared thermographic camera.

[0998] 43. The method of any one of items 1 to 43, wherein the recombinant nucleotide expression vector is administered at a dose of about 6.0 x 10 10 genome copies per eye.

[0999] 44. The method of any one of items 1 to 43, wherein the recombinant nucleotide expression vector is administered at a dose of about 1.6 x 10 11 genome copies per eye.

[1000] 45. The method of any one of items 1 to 43, wherein the recombinant nucleotide expression vector is administered at a dose of about 2.5 x 10 11 genome copies per eye.

[1001] 46. The method of any one of items 1 to 43, wherein the recombinant nucleotide expression vector is administered at a dose of about 5.0 x 10 11 genome copies per eye.

[1002] 47. The method of any one of items 1 to 43, wherein the recombinant nucleotide expression vector is administered at a dose of about 3.0 x 10 12 genome copies per eye. BRIEF DESCRIPTION OF DRAWINGS

[1003] Figure 2 . Suprachoroidal drug delivery device manufactured by Clearside® Biomedical, Inc.

[1004] Figure 3 . Subretinal drug delivery device manufactured by Janssen Pharmaceuticals, Inc. that includes a catheter that can be inserted through the suprachoroidal space toward the posterior pole and a small needle that injects into the subretinal space at the posterior pole.

[1005] Figures 4A-4D . Diagram of a human eye with a cross-sectional view.

[1006] Figure 5 . Diagram of a posterior juxtascleral reservoir procedure.

[1007] Figure 6 . Schematic of the AAV8-anti-VEGF fab genome.

[1008] Figure 7A. Monitoring of heat distribution after suprachoroidal injection using an infrared thermal camera.

[1009] Figure 7B and Figure 8A . Microsyringe drug delivery device manufactured by Altaviz.

[1010] Figure 8B and Figure 8A . Drug delivery device manufactured by Visionisti OY. In particular, Figure 8B Depiction of an injection adapter that is able to convert a 30 g short hypodermic needle into a suprachoroidal / subretinal needle. The device is able to control the length of the needle tip that is exposed from the distal end of the adapter. This can be adjusted in 10 µL steps. The device has the ability to adjust suprachoroidal delivery and / or sclerotomy subretinal delivery. SEQ ID NO. Depiction of a needle adapter guide that is able to keep the cap open and hold the needle at the optimal angle and depth for delivery. The needle adapter is locked into a stabilizing device. The needle adapter is an all-in-one tool for standardized and optimized outpatient suprachoroidal and / or subretinal injections. DETAILED DESCRIPTION

[1011] Provided herein are compositions and methods for delivering a therapeutic product, such as a therapeutic protein (e.g., an antibody), a therapeutic RNA (e.g., shRNA, siRNA, and miRNA), and a therapeutic aptamer, to the retina / vitreous humor of an eye of a human subject for treating an ocular condition, involving, for example, a recombinant viral vector, such as a recombinant adeno-associated viral (rAAV) vector.

[1012] The therapeutic product can be, for example, a therapeutic protein (e.g., an antibody), a therapeutic RNA (e.g., shRNA, siRNA, and miRNA), or a therapeutic aptamer.

[1013] In a particular embodiment, the therapeutic product is a human protein or an antibody to a human protein. Antibodies include, but are not limited to, monoclonal antibodies, polyclonal antibodies, recombinantly produced antibodies, human antibodies, humanized antibodies, chimeric antibodies, synthetic antibodies, tetrameric antibodies comprising two heavy chains and two light chain molecules, antibody light chain monomers, antibody heavy chain monomers, antibody light chain dimers, antibody heavy chain dimers, antibody light chain-heavy chain pairs, intrabodies, heteroconjugate antibodies, univalent antibodies, antigen binding fragments of full length antibodies, and fusion proteins of the foregoing. Such antigen binding fragments include, but are not limited to, single domain antibodies (variable domains of heavy chain antibodies (VHH) or nanobodies), Fabs, F(ab')2, and scFv (single chain variable fragment). In particular embodiments, the therapeutic product (e.g., therapeutic protein) is post-translationally modified. In a particular embodiment, the post-translational modification is specific to the cell type to which the therapeutic product (e.g., therapeutic protein) is delivered using a particular approach as described herein. Delivery can be achieved via gene therapy, e.g., by administering a recombinant viral vector or a recombinant DNA expression construct (collectively, “recombinant vector”) encoding the therapeutic product to the suprachoroidal space, subretinal space (via vitrectomy or without vitrectomy (e.g., through a catheter through the suprachoroidal space or via peripheral injection), intraretinal space, vitreous cavity, and / or the outer surface of the sclera (i.e., juxtascleral administration) of the eye of a human patient to create a permanent reservoir in the eye that continuously supplies the therapeutic product (e.g., post-translationally modified therapeutic product).

[1014] 6.1 Methods for delivering a therapeutic product

[1015] In one aspect, provided herein is a method of subretinal administration for treating an ocular condition without vitrectomy, comprising administering to the subretinal space in the eye of a human subject in need of treatment a recombinant viral vector comprising a nucleotide sequence encoding a therapeutic product, such that the therapeutic product is expressed and treats the ocular condition, wherein the method does not include performing a vitrectomy on the eye of the human patient. In certain embodiments, the administering step comprises administering the recombinant viral vector therapeutic product to the subretinal space of the eye of the human subject via the suprachoroidal space of the eye of the human subject. In certain embodiments, the administering step is by using a subretinal drug delivery device comprising a catheter that can be inserted through and toward the posterior pole of the suprachoroidal space, a small needle that injects into the subretinal space at the posterior pole. In certain embodiments, the administering step comprises inserting the catheter of the subretinal drug delivery device through the suprachoroidal space.

[1016] In another aspect, provided herein is a method for treating an eye condition comprising administering to the subretinal space of an eye of a human subject in need of treatment a recombinant viral vector comprising a nucleotide sequence encoding a therapeutic product, such that the therapeutic product is expressed and the eye condition is treated, wherein the method does not comprise performing a vitrectomy on the eye of the human patient. In certain embodiments, the administering step comprises administering the recombinant viral vector therapeutic product to the subretinal space of the eye of the human subject via the suprachoroidal space of the eye of the human subject. In certain embodiments, the administering step is by use of a subretinal drug delivery device comprising a catheter that can be inserted through the suprachoroidal space and towards the posterior pole, a small needle at the posterior pole to inject into the subretinal space. In certain embodiments, the administering step comprises inserting the catheter of the subretinal drug delivery device through the suprachoroidal space.

[1017] In another aspect, provided herein is a method for treating an eye condition comprising administering to the subretinal space of an eye of a human subject in need of treatment a recombinant viral vector comprising a nucleotide sequence encoding a therapeutic product, such that the therapeutic product is expressed and the eye condition is treated, wherein the method does not comprise performing a vitrectomy on the eye of the human patient. In certain embodiments, the administering step comprises administering the recombinant viral vector therapeutic product to the subretinal space of the eye of the human subject via the suprachoroidal space of the eye of the human subject. In certain embodiments, the administering step is by use of a subretinal drug delivery device comprising a catheter that can be inserted through the suprachoroidal space and towards the posterior pole, a small needle at the posterior pole to inject into the subretinal space. In certain embodiments, the administering step comprises inserting the catheter of the subretinal drug delivery device through the suprachoroidal space.

[1018] In another aspect, provided herein is a method for treating an eye condition comprising administering to the subretinal space of an eye of a human subject in need of treatment a recombinant viral vector comprising a nucleotide sequence encoding a therapeutic product, such that the therapeutic product is expressed and the eye condition is treated, wherein the method does not comprise performing a vitrectomy on the eye of the human patient. In certain embodiments, the administering step comprises administering the recombinant viral vector therapeutic product to the subretinal space of the eye of the human subject via the suprachoroidal space of the eye of the human subject. In certain embodiments, the administering step is by use of a subretinal drug delivery device comprising a catheter that can be inserted through the suprachoroidal space and towards the posterior pole, a small needle at the posterior pole to inject into the subretinal space. In certain embodiments, the administering step comprises inserting the catheter of the subretinal drug delivery device through the suprachoroidal space.

[1019] In another aspect, provided herein is a method for treating an eye condition comprising administering to the subretinal space of an eye of a human subject in need of treatment a recombinant viral vector comprising a nucleotide sequence encoding a therapeutic product, such that the therapeutic product is expressed and the eye condition is treated, wherein the method does not comprise performing a vitrectomy on the eye of the human patient. In certain embodiments, the administering step comprises administering the recombinant viral vector therapeutic product to the subretinal space of the eye of the human subject via the suprachoroidal space of the eye of the human subject. In certain embodiments, the administering step is by use of a subretinal drug delivery device comprising a catheter that can be inserted through the suprachoroidal space and towards the posterior pole, a small needle at the posterior pole to inject into the subretinal space. In certain embodiments, the administering step comprises inserting the catheter of the subretinal drug delivery device through the suprachoroidal space.

[1020] In another aspect, provided herein is a method for treating an eye condition comprising administering to the suprachoroidal space of an eye of a human subject in need of treatment a recombinant viral vector comprising a nucleotide sequence encoding a therapeutic product, such that the therapeutic product is expressed and the eye condition is treated. In certain embodiments, the administering step is by injection of the recombinant viral vector into the suprachoroidal space using a suprachoroidal drug delivery device. In certain embodiments, the suprachoroidal drug delivery device is a microinjector.

[1021] In certain embodiments, the methods and / or devices described and disclosed in International Publication Nos. WO 2016 / 042162, WO 2017 / 046358, WO 2017 / 158365, and WO 2017 / 158366 can be used to perform delivery to the subretinal space or suprachoroidal space, each of which is incorporated by reference herein in its entirety.

[1022] In another aspect, provided herein is a method for treating an eye condition comprising administering to the suprachoroidal space of an eye of a human subject in need of treatment a recombinant viral vector comprising a nucleotide sequence encoding a therapeutic product, such that the therapeutic product is expressed and the eye condition is treated. In certain embodiments, the administering step is by injection of the recombinant viral vector into the suprachoroidal space using a suprachoroidal drug delivery device. In certain embodiments, the suprachoroidal drug delivery device is a microinjector.

[1023] In another aspect, provided herein is a method for treating an eye condition comprising administering to the suprachoroidal space of an eye of a human subject in need of treatment a recombinant viral vector comprising a nucleotide sequence encoding a therapeutic product, such that the therapeutic product is expressed and the eye condition is treated. In certain embodiments, the administering step is by injection of the recombinant viral vector into the suprachoroidal space using a suprachoroidal drug delivery device. In certain embodiments, the suprachoroidal drug delivery device is a microinjector.

[1024] In one aspect, provided herein is a method for intravitreal administration for treating an ocular condition, comprising administering to the vitreous cavity of an eye of a human subject in need of treatment a recombinant viral vector comprising a nucleotide sequence encoding a therapeutic product, such that the therapeutic product is expressed and treats the ocular condition. In certain embodiments, the administering step is by injection of the recombinant viral vector into the vitreous cavity using an intravitreal drug delivery device. In certain embodiments, the intravitreal drug delivery device is a microinjector. In another aspect, provided herein is a method for treating an ocular condition, comprising administering to the vitreous cavity of an eye of a human subject in need of treatment a recombinant viral vector comprising a nucleotide sequence encoding a therapeutic product, such that the therapeutic product is expressed and treats the ocular condition. In certain embodiments, the administering step is by injection of the recombinant viral vector into the vitreous cavity using an intravitreal drug delivery device. In certain embodiments, the intravitreal drug delivery device is a microinjector.

[1025] In certain embodiments, the therapeutic product is not an anti-human vascular endothelial growth factor (hVEGF) antibody.

[1026] In certain embodiments, the ocular condition is not associated with neovascular age-related macular degeneration (nAMD), also known as the “wet” neovascular form of AMD (“WAMD” or “wet AMD”).

[1027] In certain embodiments, the therapeutic product is an anti-hVEGF antibody.

[1028] In certain embodiments, the ocular condition is associated with nAMD.

[1029] In certain embodiments, the ocular condition is associated with nAMD, and the therapeutic product is an anti-hVEGF antibody.

[1030] In one aspect, provided herein is a method for subretinal administration for treating an ocular condition with vitrectomy, comprising administering to the subretinal space of an eye of a human subject in need of treatment a recombinant viral vector comprising a nucleotide sequence encoding a therapeutic product, such that the therapeutic product is expressed and treats the ocular condition, wherein the method comprises performing a vitrectomy on the eye of the human patient, and wherein the therapeutic product is not an anti-human vascular endothelial growth factor (hVEGF) antibody. In certain embodiments, the ocular condition is an ocular disease or a disease involving multiple organs including the eye. In certain embodiments, the vitrectomy is a partial vitrectomy.

[1031] In another aspect, provided herein is a method for treating an eye condition, comprising administering to the subretinal space of an eye of a human subject in need of treatment a recombinant viral vector comprising a nucleotide sequence encoding a therapeutic product, such that the therapeutic product is expressed and the eye condition is treated, wherein the method comprises performing a vitrectomy on the eye of the human patient, and wherein the therapeutic product is not an anti-human vascular endothelial growth factor (hVEGF) antibody. In certain embodiments, the eye condition is an ocular disease or a disease involving multiple organs including the eye. In certain embodiments, the vitrectomy is a partial vitrectomy.

[1032] In one aspect, provided herein is a method for treating an eye condition by subretinal administration, comprising administering a recombinant viral vector comprising a nucleotide sequence encoding a therapeutic product to the subretinal space of the posterior of the eye of a human subject in need of treatment, such that the therapeutic product is expressed and the eye condition is treated, wherein the method does not comprise performing a vitrectomy on the eye of the human patient. In certain embodiments, the injecting step is by transvitreal injection. In certain embodiments, the method of transvitreal administration results in uniform expression of the therapeutic product throughout the eye (e.g., less than 5%, 10%, 20%, 30%, 40%, or 50% variation in expression at the site of injection compared to the amount of expression in other regions of the eye). In certain embodiments, the transvitreal injection comprises inserting a sharp needle into the sclera via the superior or inferior side of the eye and passing the sharp needle completely through the vitreous body to inject the recombinant viral vector into the subretinal space on the other side. In certain embodiments, the needle is inserted at the 2 o'clock or 10 o'clock position. In certain embodiments, the transvitreal injection comprises inserting a trocar into the sclera and inserting a cannula through the trocar and through the vitreous body to inject the recombinant viral vector into the subretinal space on the other side. In certain embodiments, the therapeutic product is an anti-hVEGF antibody. In certain embodiments, the anti-hVEGF antibody is an anti-hVEGF antigen-binding fragment. In certain embodiments, the anti-hVEGF antigen-binding fragment is a Fab, F(ab')2, or single chain variable fragment (scFv). In certain embodiments, the anti-hVEGF antibody contains a heavy chain comprising the amino acid sequence of SEQ ID NO: 2 or SEQ ID NO: 4 and a light chain comprising the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 3. In certain embodiments, wherein the anti-hVEGF antibody comprises light chain CDRs 1-3 of SEQ ID NO: 14-16 and heavy chain CDRs 1-3 of SEQ ID NO: 17-19 or SEQ ID NO: 20, 18, and 21. In certain embodiments, wherein the eye condition is associated with nAMD, dry age-related macular degeneration (dry AMD), retinal vein occlusion (RVO), diabetic macular edema (DME), or diabetic retinopathy (DR). In certain embodiments, the eye condition is associated with nAMD.

[1033] In another aspect, provided herein is a method for treating an eye condition comprising administering to the subretinal space of the optic disc, fovea and macular periphery of the posterior of the eye of a human subject in need of treatment a recombinant viral vector comprising a nucleotide sequence encoding a therapeutic product, such that the therapeutic product is expressed and the eye condition is treated, wherein the method does not comprise performing a vitrectomy on the eye of the human patient. In certain embodiments, the step of injecting is by intravitreal injection. In certain embodiments, the method of intravitreal administration results in uniform expression of the therapeutic product throughout the eye (e.g., less than 5%, 10%, 20%, 30%, 40%, or 50% variation in expression at the site of injection compared to the amount of expression in other regions of the eye). In certain embodiments, the intravitreal injection comprises inserting a sharp needle into the sclera via the superior or inferior side of the eye and passing the sharp needle completely through the vitreous body to inject the recombinant viral vector into the subretinal space on the other side. In certain embodiments, the needle is inserted at the 2 o'clock or 10 o'clock position. In certain embodiments, the intravitreal injection comprises inserting a trocar into the sclera and inserting a cannula through the trocar and through the vitreous body to inject the recombinant viral vector into the subretinal space on the other side. In certain embodiments, the therapeutic product is an anti-hVEGF antibody. In certain embodiments, the anti-hVEGF antibody is an anti-hVEGF antigen-binding fragment. In certain embodiments, the anti-hVEGF antigen-binding fragment is a Fab, F(ab')2, or single chain variable fragment (scFv). In certain embodiments, the anti-hVEGF antibody contains a heavy chain comprising the amino acid sequence of SEQ ID NO: 2 or SEQ ID NO: 4 and a light chain comprising the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 3. In certain embodiments, wherein the anti-hVEGF antibody comprises the light chain CDRs 1-3 of SEQ ID NOs: 14-16 and the heavy chain CDRs 1-3 of SEQ ID NOs: 17-19 or SEQ ID NOs: 20, 18, and 21. In certain embodiments, wherein the eye condition is associated with nAMD, dry age-related macular degeneration (dry AMD), retinal vein occlusion (RVO), diabetic macular edema (DME), or diabetic retinopathy (DR). In certain embodiments, the eye condition is associated with nAMD.

[1034] In certain embodiments of the methods described herein, the step of administering delivers a therapeutically effective amount of the therapeutic product to the retina of the human subject.

[1035] In certain embodiments of the methods described herein, the therapeutically effective amount of the therapeutic product is produced by the human retinal cells of the human subject.

[1036] In certain embodiments of the methods described herein, the therapeutically effective amount of the therapeutic product is produced by human photoreceptor cells, horizontal cells, bipolar cells, amacrine cells, retinal ganglion cells, and / or retinal pigment epithelial cells in the outer limiting membrane of the human subject.

[1037] In certain embodiments of the methods described herein, the human photoreceptor cells are cone cells and / or rod cells.

[1038] In certain embodiments of the methods described herein, the retinal ganglion cells are dwarf cells, umbrella cells, biiayer cells, giant retinal ganglion cells, photosensitive ganglion cells, and / or Muller glial cells.

[1039] In certain embodiments of the methods described herein, the recombinant viral vector is a rAAV vector (e.g., a rAAV8, rAAV2, rAAV2tYF, or rAAV5 vector).

[1040] In certain embodiments of the methods described herein, wherein the recombinant viral vector is a rAAV8 vector.

[1041] In certain embodiments of the methods described herein, delivering to the eye comprises delivering to the retina, choroid, and / or vitreous humor of the eye.

[1042] 6.1.1 Post-translational modifications

[1043] In certain embodiments, the therapeutic product (e.g., therapeutic protein) is post- translationally modified. In a particular embodiment, the post-translational modification is specific to the cell type to which the therapeutic product (e.g., therapeutic protein) is delivered using a particular route as described herein.

[1044] In a particular embodiment, the post-translational modification is glycosylation. In another particular embodiment, the post-translational modification is tyrosine sulfation. In another particular embodiment, the post-translational modification is phosphorylation. In another particular embodiment, the post-translational modification is ADP-ribosylation. In another particular embodiment, the post-translational modification is prenylation. In another particular embodiment, the post-translational modification is myristoylation or palmitoylation. In another particular embodiment, the post-translational modification is ubiquitination. In another particular embodiment, the post-translational modification is small ubiquitin-like protein modification. In another particular embodiment, the post-translational modification is ubiquitination-like protein modification.

[1045] In a particular embodiment, the therapeutic product is post-translationally modified upon expression from the recombinant vector in human immortalized retinal-derived cells.

[1046] In a particular embodiment, administration of the recombinant vector results in the formation of a reservoir that releases a therapeutic product containing a post-translational modification.

[1047] In a particular embodiment, the recombinant vector, when used to transduce retinal-derived cells in culture, results in the production of a therapeutic product containing a post-translational modification.

[1048] Post-translational modifications can be detected by any method known in the art for detecting post-translational modifications, such as Western blotting, chromatography, or flow cytometry.

[1049] In a particular embodiment, post-translation can be detected by in vivo labeling of cellular substrate pools with a radioactive substrate or substrate precursor molecule that results in the incorporation of a radiolabeled moiety, including but not limited to a phosphate group, a fatty acyl group (e.g., myristoyl or palmitoyl), a small ubiquitin-like protein, a methyl group, an acetyl group, a hydroxyl group, an iodine, a flavin, ubiquitin, or an ADP-ribose group into the therapeutic product. Analysis of the modified protein is typically performed by electrophoresis and autoradiography, with increased specificity by immunoprecipitation of the protein of interest prior to electrophoresis.

[1050] In a particular embodiment, post-translation can be detected by in vitro enzymatic incorporation of a labeled moiety (including but not limited to a radioactive, luminescent, or fluorescent label) into the therapeutic product to estimate the state of modification in vivo.

[1051] In a particular embodiment, post-translation can be detected by analyzing the change in electrophoretic mobility of the modified therapeutic product (e.g., glycosylation or ubiquitination) compared to the unmodified therapeutic product.

[1052] In a particular embodiment, post-translation can be detected by thin layer chromatography of radiolabeled fatty acids extracted from the therapeutic product.

[1053] In a particular embodiment, post-translation can be detected by partitioning of the therapeutic product into a detergent-rich layer or detergent layer using phase separation, and the effect of enzymatic treatment of the therapeutic product on partitioning between aqueous and detergent-rich environments.

[1054] In a particular embodiment, post-translation can be detected by antibody recognition of the form of the protein modification, such as by Western blotting or flow cytometry.

[1055] 6.1.2 Constructs and Formulations

[1056] For use in the methods provided herein are recombinant viral vectors or other recombinant DNA expression constructs (collectively, "recombinant vectors") that encode a therapeutic product. The recombinant viral vectors and other DNA expression constructs provided herein include any suitable for delivering a therapeutic product (such as a therapeutic protein (e.g., an antibody), a therapeutic RNA (e.g., shRNA, siRNA, and miRNA), and a therapeutic aptamer) to a target cell (e.g., a retinal pigment epithelial cell). Modes of delivery of a therapeutic product include recombinant viral vectors, liposomes, other lipid-containing complexes, other macromolecular complexes, synthetic modified mRNA, unmodified mRNA, small molecules, non-biologically active molecules (e.g., gold particles), polymeric molecules (e.g., dendrimers), naked DNA, plasmids, bacteriophages, transposons, cosmids, or episomes. In some embodiments, the vector is a targeted vector, e.g., a vector that targets a retinal pigment epithelial cell.

[1057] In some aspects, the disclosure provides a nucleic acid for use, wherein the nucleic acid encodes a therapeutic product operably linked to a promoter or enhancer-promoter described herein.

[1058] In certain embodiments, provided herein are recombinant vectors comprising one or more nucleic acids (e.g., polynucleotides). The nucleic acids can comprise DNA, RNA, or a combination of DNA and RNA. In certain embodiments, the DNA comprises one or more of a sequence selected from the group consisting of a promoter sequence, a sequence encoding a therapeutic product of interest, an untranslated region, and a termination sequence. In certain embodiments, the recombinant vectors provided herein comprise a promoter operably linked to a sequence encoding a therapeutic product of interest.

[1059] In certain embodiments, the nucleic acids (e.g., polynucleotides) and nucleic acid sequences disclosed herein can be codon optimized, e.g., via any codon optimization technique known to one of skill in the art (see, e.g., the review by Quax et al., 2015, Mol Cell 59: 149-161).

[1060] (a) mRNA

[1061] In certain embodiments, the recombinant vectors provided herein comprise a modified mRNA encoding a therapeutic product of interest. The synthesis of modified and unmodified mRNA for delivery of a therapeutic product to a cell of the eye, e.g., a retinal pigment epithelial cell, is taught, e.g., in Hansson et al., J. Biol. Chem., 2015, 290(9):5661-5672, which is incorporated by reference herein in its entirety. In certain embodiments, provided herein is a modified mRNA encoding a portion of a therapeutic product.

[1062] (b) shRNA, siRNA, and miRNA

[1063] In certain embodiments, the recombinant vectors provided herein comprise a nucleotide sequence encoding a therapeutic product that is an shRNA, siRNA, or miRNA.

[1064] (c) recombinant viral vectors

[1065] Recombinant viral vectors include recombinant adenovirus, adeno-associated virus (AAV, e.g., AAV1, AAV2, AAV2tYF, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10, AAV11, and AAVrh10), lentivirus, helper-dependent adenovirus, herpes simplex virus, poxvirus, hemagglutinating virus of Japan (HVJ), alphavirus, vaccinia virus, and retroviral vectors. Retroviral vectors include vectors based on mouse leukemia virus (MLV) and human immunodeficiency virus (HIV). Alphavirus vectors include semliki forest virus (SFV) and sindbis virus (SIN). In certain embodiments, the recombinant viral vectors provided herein are altered so that they are replication-deficient in humans. In certain embodiments, the recombinant viral vectors are hybrid vectors, e.g., AAV vectors placed in a “helperless” adenoviral vector. In certain embodiments, recombinant viral vectors are provided herein that comprise a viral capsid from a first virus and viral envelope proteins from a second virus. In particular embodiments, the second virus is vesicular stomatitis virus (VSV). In more particular embodiments, the envelope proteins are VSV-G proteins.

[1066] In certain embodiments, the recombinant viral vectors provided herein are HIV-based viral vectors. In certain embodiments, the HIV-based vectors provided herein comprise at least two polynucleotides, wherein the gag and pol genes are from an HIV genome and the env gene is from another virus.

[1067] In certain embodiments, the recombinant viral vectors provided herein are herpes simplex virus-based viral vectors. In certain embodiments, the herpes simplex virus-based vectors provided herein are modified so that they do not comprise one or more immediate early (IE) genes, rendering them non-cytotoxic.

[1068] In certain embodiments, the recombinant viral vectors provided herein are MLV-based viral vectors. In certain embodiments, the MLV-based vectors provided herein comprise up to 8 kb of heterologous DNA in place of viral genes.

[1069] In certain embodiments, the recombinant viral vectors provided herein are lentivirus-based viral vectors. In certain embodiments, the lentivirus vectors provided herein are derived from human lentiviruses. In certain embodiments, the lentivirus vectors provided herein are derived from non-human lentiviruses. In certain embodiments, the lentivirus vectors provided herein are packaged in a lentiviral capsid. In certain embodiments, the lentivirus vectors provided herein comprise one or more of the following elements: long terminal repeat sequences, primer binding sites, a polypurine tract, an att site, and a encapsidation site.

[1070] In certain embodiments, the recombinant viral vectors provided herein are alphavirus- based viral vectors. In certain embodiments, the alphavirus vectors provided herein are recombinant replication-deficient alphaviruses. In certain embodiments, the alphavirus replicon in the alphavirus vectors provided herein is targeted to specific cell types by presenting a functional heterologous ligand on the surface of its virion.

[1071] In certain embodiments, the recombinant viral vectors provided herein are AAV-based viral vectors. In preferred embodiments, the recombinant viral vectors provided herein are AAV8- based viral vectors. In certain embodiments, the AAV8-based viral vectors provided herein retain the tropism of retinal cells. In certain embodiments, the AAV-based vectors provided herein encode an AAV rep gene (required for replication) and / or an AAV cap gene (required for capsid protein synthesis). A number of AAV serotypes have been identified. In certain embodiments, the AAV-based vectors provided herein comprise components from one or more AAV serotypes. In certain embodiments, the AAV-based vectors provided herein comprise capsid components from one or more of AAV1, AAV2, AAV2tYF, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10, AAV11, or AAVrh10. In preferred embodiments, the AAV-based vectors provided herein comprise components from one or more of the AAV8, AAV9, AAV10, AAV11, or AAVrh10 serotypes.

[1072] Provided in particular embodiments is an AAV8 vector comprising a viral genome comprising an expression cassette for expressing a therapeutic product under the control of a regulatory element and flanked by ITRs, and a viral capsid having an amino acid sequence of an AAV8 capsid protein or at least 95%, 96%, 97%, 98%, 99%, or 99.9% identical to the amino acid sequence of an AAV8 capsid protein (SEQ ID NO: 48) while retaining the biological function of an AAV8 capsid. In certain embodiments, the encoded AAV8 capsid has the sequence of SEQ ID NO: 48 with 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 amino acid substitutions and retains the biological function of an AAV8 capsid.

[1073] In certain embodiments, the AAV used in the methods described herein is Anc80 or Anc80L65, as described in Zinn et al., 2015, Cell Rep. 12(6): 1056-1068, which is incorporated by reference in its entirety herein. In certain embodiments, the AAV used in the methods described herein comprises one of the following amino acid insertions: LGETTRP or LALGETTRP, as described in U.S. Patent Nos. 9,193,956; 9458517; and 9,587,282 and U.S. Patent Application Publication No. 2016 / 0376323, each of which is incorporated by reference in its entirety herein. In certain embodiments, the AAV used in the methods described herein is AAV.7m8, as described in U.S. Patent Nos. 9,193,956; 9,458,517; and 9,587,282 U.S. Patent Application Publication No. 2016 / 0376323, each of which is incorporated by reference in its entirety herein. In certain embodiments, the AAV used in the methods described herein is any of the AAVs disclosed in U.S. Patent No. 9,585,971, such as AAV-PHP.B. In certain embodiments, the AAV used in the methods described herein is an AAV disclosed in any of the following patents and patent applications, each of which is incorporated by reference in its entirety herein: U.S. Patent Nos. 7,906,111; 8,524,446; 8,999,678; 8,628,966; 8,927,514; 8,734,809; US 9,284,357; 9,409,953; 9,169,299; 9,193,956; 9458517; and 9,587,282; U.S. Patent Application Publication Nos. 2015 / 0374803; 2015 / 0126588; 2017 / 0067908; 2013 / 0224836; 2016 / 0215024; 2017 / 0051257; and International Patent Application Nos. PCT / US2015 / 034799; PCT / EP2015 / 053335.

[1074] AAV8-based viral vectors are used in certain embodiments of the methods described herein. Nucleic acid sequences of AAV-based viral vectors and methods of making recombinant AAV and AAV capsids are taught, for example, in U.S. Patent No. 7,282,199 B2, U.S. Patent No. 7,790,449 B2, U.S. Patent No. 8,318,480 B2, U.S. Patent No. 8,962,332 B2, and International Patent Application No. PCT / EP2014 / 076466, each of which is incorporated by reference in its entirety herein. In one aspect, provided herein are AAV (e.g., AAV8)-based viral vectors encoding a therapeutic product.

[1075] In certain embodiments, single-stranded AAV (ssAAV) can be used above. In certain embodiments, self-complementary vectors, such as scAAV, can be used (see, e.g., Wu, 2007, Human Gene Therapy, 18(2): 171-82, McCarty et al., 2001, Gene Therapy, Vol. 8, No. 16, pp. 1248-1254; and U.S. Patent Nos. 6,596,535; 7,125,717; and 7,456,683, each of which is incorporated by reference herein in its entirety).

[1076] In certain embodiments, the recombinant viral vector used in the methods described herein is a recombinant adenoviral vector. The recombinant adenovirus can be a first generation vector with an El deletion, with or without an E3 deletion, and with an expression cassette inserted in either deletion region. The recombinant adenovirus can be a second generation vector containing a total or partial deletion of the E2 and E4 regions. Helper cell-dependent adenoviruses retain only the adenovirus inverted terminal repeats and the packaging signal (phi). The therapeutic product is inserted between the packaging signal and the 3’ ITR, with or without a stuffer sequence to bring the genome close to the wild-type size of about 36 kb. Exemplary protocols for generating adenoviral vectors can be found in Alba et al., 2005, “Gutless adenovirus: last generation adenovirus for gene therapy,” Gene Therapy 12:S18-S27, which is incorporated by reference herein in its entirety.

[1077] In certain embodiments, the recombinant viral vector used in the methods described herein is a lentivirus-based viral vector. Four plasmids are used to make the construct: a plasmid containing the Gag / pol sequences, a plasmid containing the Rev sequences, a plasmid containing the envelope protein (i.e., VSV-G), and a Cis plasmid with packaging elements and a plasmid containing the therapeutic product.

[1078] To manufacture lentiviral vectors, four plasmids are co-transfected into cells (i.e., HEK293-based cells), where, among other things, polyethyleneimine or calcium phosphate can be used as the transfection agent. Lentivirus is then harvested in the supernatant (lentivirus needs to bud from the cells to be active, so no cell harvest is required / should be performed). The supernatant is filtered (0.45 pm) and then magnesium chloride and nuclease are added. Further downstream processes can vary greatly, with the use of TFF and column chromatography being the most GMP-compatible methods. Other methods use ultracentrifugation with / without column chromatography. Exemplary protocols for manufacturing lentiviral vectors can be found in Lesch et al., 2011, “Production and purification of lentiviral vector generated in 293T suspension cells with baculoviral vectors,” Gene Therapy 18:531-538 and Ausubel et al., 2012, “Production of CGMP-Grade Lentiviral Vectors,” Bioprocess Int. 10(2):32-43, both of which are incorporated by reference herein in their entireties.

[1079] (d) Promoters and modifiers of gene expression

[1080] In certain embodiments, the recombinant vectors provided herein comprise components that modulate delivery or expression of the therapeutic product (e.g., “expression control elements”). In certain embodiments, the recombinant vectors provided herein comprise components that modulate expression of the therapeutic product. In certain embodiments, the recombinant vectors provided herein comprise components that affect binding or targeting of cells. In certain embodiments, the recombinant vectors provided herein comprise components that affect the localization of the polynucleotide encoding the therapeutic product within the cell after uptake. In certain embodiments, the recombinant vectors provided herein comprise components that can be used as detectable or selectable markers, e.g., to detect or select for cells that have taken up the polynucleotide encoding the therapeutic product.

[1081] In certain embodiments, the recombinant vectors provided herein comprise one or more promoters. In certain embodiments, the promoter is a constitutive promoter. In certain embodiments, the promoter is an inducible promoter. Inducible promoters can be preferred so that expression of the therapeutic product can be turned on and off as needed for therapeutic efficacy. Such promoters include, for example, hypoxia-inducible promoters and drug-inducible promoters, such as promoters induced by rapamycin and related agents. Hypoxia-inducible promoters include promoters with HIF binding sites, see, e.g., Schodel et al., 2011, Blood 117(23):e207-e217 and Kenneth and Rocha, 2008, Biochem J. 414:19-29, each of which is incorporated by reference for its teachings of hypoxia-inducible promoters. Additionally, hypoxia-inducible promoters that can be used in the constructs include the erythropoietin promoter and the N-WASP promoter (see Tsuchiya, 1993, J. Biochem. 113:395 for disclosure of the erythropoietin promoter and Salvi, 2017, Biochemistry and Biophysics Reports 9:13-21 for disclosure of the N-WASP promoter, each of which is incorporated by reference for its teachings of hypoxia-inducible promoters). Alternatively, the recombinant vectors can contain drug-inducible promoters, such as promoters induced by administration of rapamycin and related analogs (see, e.g., International Patent Application Publication Nos. WO 94 / 18317, WO 96 / 20951, WO 96 / 41865, WO 99 / 10508, WO 99 / 10510, WO 99 / 36553, and WO 99 / 41258, and U.S. Patent No. US 7,067,526 (disclosing rapamycin analogs), the disclosures of which regarding drug-inducible promoters are incorporated herein by reference). In certain embodiments, the promoter is a hypoxia-inducible promoter. In certain embodiments, the promoter comprises a hypoxia-inducible factor (HIF) binding site. In certain embodiments, the promoter comprises a HIF-1a binding site. In certain embodiments, the promoter comprises a HIF-2a binding site. In certain embodiments, the HIF binding site comprises a RCGTG motif. For details on the location and sequence of the HIF binding site, see, e.g., Schodel et al., Blood, 2011, 117(23):e207-e217, which is incorporated by reference in its entirety. In certain embodiments, the promoter comprises a binding site for a hypoxia-inducible transcription factor other than a HIF transcription factor. In certain embodiments, the recombinant vectors provided herein comprise one or more IRES sites that are preferentially translated in hypoxia.For teachings regarding hypoxia-inducible gene expression and factors involved therein, see, e.g., Kenneth and Rocha, Biochem J., 2008, 414:19-29, which is incorporated by reference herein in its entirety.

[1082] In certain embodiments, the promoter is a CB7 promoter (see Dinculescu et al., 2005, Hum Gene Ther 16: 649-663, which is incorporated by reference herein in its entirety). In certain embodiments, the CB7 promoter includes other expression control elements that enhance expression of the therapeutic product driven by the vector, such as (1) a CAG promoter; (2) a CBA promoter; (3) a CMV promoter; (4) a 1.7 kb red cone opsin promoter (PR1.7 promoter); (5) a rhodopsin kinase (GRK1) photoreceptor-specific enhancer-promoter (Young et al., 2003, Retinal Cell Biology; 44:4076-4085); (6) a hCARp promoter, which is a human cone arrestin promoter; (7) a hRKp, which is a rhodopsin kinase promoter; (8) a cone photoreceptor-specific human arrestin 3 (ARR3) promoter; (9) a rhodopsin promoter; and (10) a U6 promoter (especially when the therapeutic product is a small RNA such as shRNA and siRNA).

[1083] In certain embodiments, other expression control elements include a chicken beta-actin intron and / or a rabbit beta-globin polA signal. In certain embodiments, the promoter comprises a TATA box. In certain embodiments, the promoter comprises one or more elements. In certain embodiments, one or more promoter elements can be inverted or moved relative to one another. In certain embodiments, the elements of the promoter are positioned to act in concert. In certain embodiments, the elements of the promoter are positioned to act independently. In certain embodiments, the recombinant vectors provided herein comprise one or more promoters selected from the group consisting of a human CMV immediate early gene promoter, an SV40 early promoter, a Rous sarcoma virus (RS) long terminal repeat, and a rat insulin promoter. In certain embodiments, the recombinant vectors provided herein comprise one or more long terminal repeat (LTR) promoters selected from the group consisting of AAV, MLV, MMTV, SV40, RSV, HIV-1, and HIV-2 LTRs. In certain embodiments, the recombinant vectors provided herein comprise one or more tissue-specific promoters (e.g., a retinal pigment epithelial cell-specific promoter). In certain embodiments, the recombinant vectors provided herein comprise a RPE65 promoter. In certain embodiments, the recombinant vectors provided herein comprise a VMD2 promoter.

[1084] In certain embodiments, the recombinant vectors provided herein comprise one or more regulatory elements in addition to a promoter. In certain embodiments, the recombinant vectors provided herein comprise an enhancer. In certain embodiments, the recombinant vectors provided herein comprise a suppressor. In certain embodiments, the recombinant vectors provided herein comprise an intron or chimeric intron. In certain embodiments, the recombinant vectors provided herein comprise a polyadenylation sequence.

[1085] (e) signal peptide

[1086] In certain embodiments in which the therapeutic product is a therapeutic protein, the recombinant vectors provided herein comprise components that modulate protein delivery. In certain embodiments, the recombinant vectors provided herein comprise one or more signal peptides. A signal peptide can also be referred to herein as a “leader sequence” or “leader peptide.” In certain embodiments, a signal peptide allows a therapeutic product to achieve proper packaging (e.g., glycosylation) in a cell. In certain embodiments, a signal peptide allows a therapeutic product to achieve proper localization in a cell. In certain embodiments, a signal peptide allows a therapeutic product to achieve secretion from a cell. Examples of signal peptides for use in conjunction with the recombinant vectors and therapeutic products provided herein can be found in Table 1.

[1087] Table 1. Signal peptides for use with the vectors provided herein.

[1088] Signal peptide Sequence VEGF-A signal peptide 5 MNFLLSWVHWSLALLLYLHHAKWSQA Fibulin-1 signal peptide 6 MERAAPSRRVPLPLLLLGGLALLAAGVDA Vitronectin signal peptide 7 MAPLRPLLILALLAWVALA Complement Factor H signal peptide 8 MRLLAKIICLMLWAICVA Rheumatoid factor signal peptide 9 MRLLAFLSLLALVLQETGT Albumin signal peptide 22 MKWVTFISLLFLFSSAYS Chymotrypsinogen signal peptide 23 MAFLWLLSCWALLGTTFG Interleukin-2 signal peptide 24 MYRMQLLSCIALILALVTNS Trypsinogen-2 signal peptide 25 MNLLLILTFVAAAVA Figure 7A

[1089] (f) Multi-cistronic messages - IRES and F2A linkers

[1090] Internal ribosome entry sites. Single constructs can be engineered to encode two peptides (e.g., heavy and light chains of an antibody) separated by a cleavable linker or an IRES, such that the two peptides (e.g., separate heavy and light chain polypeptides) are expressed by the transduced cell. In certain embodiments, the recombinant vectors provided herein provide multi-cistronic (e.g., bicistronic) messages. For example, the recombinant vectors can include nucleotide sequences encoding two peptides (e.g., heavy and light chains of an antibody) separated by an internal ribosome entry site (IRES) element (e.g., to create a bicistronic vector using an IRES element, see, e.g., Gurtu et al., 1996, Biochem. Biophys. Res. Comm. 229(1):295-8, which is incorporated by reference herein in its entirety). IRES elements bypass the ribosomal scanning model and initiate translation at an internal site. The use of IRES in AAV is described in, e.g., Furling et al., 2001, Gene Ther 8(11): 854-73, which is incorporated by reference herein in its entirety. In certain embodiments, the bicistronic message is included within a recombinant vector that has a restriction on the size of the polynucleotide therein. In certain embodiments, the bicistronic message is included within an AAV virus-based vector (e.g., an AAV8-based vector).

[1091] Furin-F2A linker. In other embodiments, the recombinant vectors provided herein include nucleotide sequences encoding two peptides (e.g., heavy and light chains of an antibody) separated by a cleavable linker such as a self-cleaving furin / F2A (F / F2A) linker (Fang et al., 2005, Nature Biotechnology 23: 584-590 and Fang, 2007, Mol Ther 15: 1153-9, each of which is incorporated by reference herein in its entirety).

[1092] For example, a furin-F2A linker can be incorporated into an expression cassette to separate the coding sequences of two peptides (e.g., heavy and light chain coding sequences), resulting in a construct having the following structure:

[1093] Leader sequence - Peptide A (e.g., heavy chain of an antibody) - Furin site - F2A site - Leader sequence - Peptide B (e.g., light chain of an antibody) - PolyA.

[1094] The F2A site having the amino acid sequence LLNFDLLKLAGDVESNPGP (SEQ ID NO: 26) is self-processing, resulting in a "cleavage" between the final G and P amino acid residues. Other linkers that can be used include, but are not limited to:

[1095] • T2A: (GSG) E G R G S L L T C G D V E E N P G P (SEQ ID NO: 27);

[1096] • P2A: (GSG) A T N F S L L K Q A G D V E E N P G P (SEQ ID NO: 28);

[1097] • E2A: (GSG) Q C T N Y A L L K L A G D V E S N P G P (SEQ ID NO: 29);

[1098] • F2A: (GSG) V K Q T L N F D L L K L A G D V E S N P G P (SEQ ID NO: 30).

[1099] When the ribosome encounters the F2A sequence in the open reading frame, the peptide bond is skipped, resulting in either termination of translation or continuation of translation of the downstream sequence (the second peptide). This self-processing sequence results in a string of additional amino acids at the end of the C-terminus of the first peptide. However, this additional string of amino acids is subsequently cleaved by host cell furin protease at a furin protease site immediately preceding the F2A site and following the sequence of the first peptide, and further cleaved by carboxypeptidases. The resulting first peptide can include one, two, three, or more additional amino acids at the C-terminus, or it can have no such additional amino acids, depending on the sequence of the furin protease linker used and the carboxypeptidases that cleave the linker in vivo (see, e.g., Fang et al., 2005 Apr 17, Nature Biotechnol. Advance Online Publication; Fang et al., 2007, Molecular Therapy 15(6): 1153-1159; Luke, 2012, Innovations in Biotechnology, Ch. 8, 161-186). Furin protease linkers that can be used include a series of four basic amino acids, such as RKRR, RRRR, RRKR, or RKKR. Once this linker is cleaved by carboxypeptidases, additional amino acids can be retained, such that zero, one, two, three, or four additional amino acids can be retained on the C-terminus of the first peptide, such as R, RR, RK, RKR, RRR, RRK, RKK, RKRR, RRRR, RRKR, or RKKR. In certain embodiments, no additional amino acids are retained once the linker is cleaved by carboxypeptidases. In certain embodiments, the furin protease linker has the sequence R-X-K / R-R, such that the additional amino acids on the C-terminus of the first peptide are R, RX, RXK, RXR, RXKR, or RXRR, where X is any amino acid, such as alanine (A). In certain embodiments, no additional amino acids are retained on the C-terminus of the first peptide.

[1100] In certain embodiments, the expression cassettes described herein are comprised within a recombinant vector, which has a restriction on the size of the polynucleotide therein. In certain embodiments, the expression cassettes are comprised within an AAV virus-based vector, such as an AAV8-based vector.

[1101] (g) untranslated region

[1102] In certain embodiments where the therapeutic product is a therapeutic protein, the recombinant vectors provided herein comprise one or more untranslated regions (UTRs), such as 3' and / or 5' UTRs. In certain embodiments, the UTRs are optimized for the amount of protein expressed. In certain embodiments, the UTRs are optimized for the half-life of the mRNA encoding the therapeutic protein. In certain embodiments, the UTRs are optimized for the stability of the mRNA encoding the therapeutic protein. In certain embodiments, the UTRs are optimized for the secondary structure of the mRNA encoding the therapeutic protein.

[1103] (h) inverted terminal repeat sequences

[1104] In certain embodiments, the recombinant viral vectors provided herein comprise one or more inverted terminal repeat (ITR) sequences. ITR sequences can be used to package the recombinant therapeutic product expression cassette into virions of the recombinant viral vector. In certain embodiments, the ITRs are from AAV, such as AAV8 or AAV2 (see, e.g., Yan et al., 2005, J. Virol., 79(1):364-379; U.S. Patent No. 7,282,199 B2, U.S. Patent No. 7,790,449 B2, U.S. Patent No. 8,318,480 B2, U.S. Patent No. 8,962,332 B2, and International Patent Application No. PCT / EP2014 / 076466, each of which is incorporated herein by reference in its entirety).

[1105] (i) therapeutic product

[1106] The therapeutic product can be, for example, a therapeutic protein (e.g., an antibody), a therapeutic RNA (e.g., shRNA, siRNA, and miRNA), or a therapeutic aptamer. Antibodies include, but are not limited to, monoclonal antibodies, polyclonal antibodies, recombinantly produced antibodies, human antibodies, humanized antibodies, chimeric antibodies, synthetic antibodies, tetrameric antibodies comprising two heavy chains and two light chain molecules, antibody light chain monomers, antibody heavy chain monomers, antibody light chain dimers, antibody heavy chain dimers, antibody light chain-heavy chain pairs, intrabodies, heteroconjugate antibodies, monovalent antibodies, antigen-binding fragments of full-length antibodies, and fusion proteins of the foregoing. Such antigen-binding fragments include, but are not limited to, single-domain antibodies (variable domains of heavy chain antibodies (VHHs) or nanobodies), Fabs, F(ab')2s, and scFv (single-chain variable fragment).

[1107] In certain embodiments of the methods described herein, the therapeutic product is: (1) an anti-human vascular endothelial growth factor (hVEGF) antibody or aptamer; (2) an anti-hVEGF antigen binding fragment; (3) the anti-hVEGF antigen binding fragment is a Fab, F(ab')2, or single chain variable fragment (scFv); (4) palmitoyl-protein thioesterase 1 (PPT1); (5) tripeptidyl-peptidase 1 (TPP1); (6) Battenin (CLN3); (7) CLN6 transmembrane ER protein (CLN6); (8) major facilitator superfamily domain containing 8 (MFSD8); (9) myosin VIIA (MY07A); (1) cadherin-related 23 (CDH23); (11) protocadherin-related 15 (PCDH15); (12) Usherin (USH2A); (13) Clarin 1 (CLRN1); (14) ATP-binding cassette subfamily A member 4 (ABCA4); (15) ELOVL fatty acid elongase 4 (ELOVL4); an anti- interleukin 6 (IL6) monoclonal antibody / aptamer; (16) an anti-TNF-a (TNF) monoclonal antibody or aptamer; (17) L-opsin (OPN1LW); (18) M-opsin (OPN1MW); (19) retinal guanylate cyclase 2D (GUCY2D); (20) retinoid isomerohydrolase RPE65 (RPE65); (21) spermatogenesis associated 7 (SPATA7); (22) aryl hydrocarbon receptor interacting protein-like 1 (AIPL1); (23) Lebercilin (LCA5); (24) RPGR interacting protein 1 (RPGRIP1); (25) cone-rod homeobox (CRX); (26) Crumbs cell polarity complex component 1 (CRB1); (27) nicotinamide nucleotide adenylyltransferase 1 (NMNAT1); (28) centrosomal protein 290 (CEP290); (29) inosine monophosphate dehydrogenase 1 (IMPDH1); (3) retinal degeneration 3, GUCY2D regulator (RD3); (31) retinol dehydrogenase 12 (RDH12); (32) lecithin retinol acyltransferase (LRAT); (33) tubby-like protein 1 (TULP1); (34) potassium voltage-gated channel subfamily J member 13 (KCNJ13); (35) mitochondrially encoded NADH dehydrogenase 1 (MT-ND1); (36) mitochondrially encoded NADH dehydrogenase 4 (MT-ND4); (37) mitochondrially encoded NADH dehydrogenase 6 (MT-ND6);(38) an anti-complement monoclonal antibody or aptamer, wherein the anti-complement monoclonal antibody or aptamer is an anti-complement Cl antibody or aptamer, an anti-complement Clq monoclonal antibody or aptamer, an anti-complement Cls monoclonal antibody or aptamer, an anti-complement C2 monoclonal antibody or aptamer, an anti-complement C2a monoclonal antibody or aptamer, an anti-complement C2b monoclonal antibody or aptamer, an anti-complement C3 monoclonal antibody or aptamer, an anti-complement C3a monoclonal antibody or aptamer, an anti-complement C3b monoclonal antibody or aptamer, an anti-complement C4 monoclonal antibody or aptamer, an anti-complement C4a monoclonal antibody or aptamer, an anti-complement C4b monoclonal antibody or aptamer, an anti-complement C5 monoclonal antibody or aptamer, an anti-complement C5a monoclonal antibody or aptamer, an anti-complement C5b monoclonal antibody or aptamer, an anti-complement C6 monoclonal antibody or aptamer, an anti-complement C7 monoclonal antibody or aptamer, an anti-complement C8 monoclonal antibody or aptamer, or an anti-complement C9 monoclonal antibody or aptamer, or preferably an anti-complement C5 antibody and the ocular condition is associated with neuromyelitis optica (NMO); (39) an anti-IL6 monoclonal antibody or aptamer and the ocular condition is associated with NMO; (40) an anti-complement monoclonal antibody or aptamer, wherein the anti-complement monoclonal antibody or aptamer is an anti-complement Cl monoclonal antibody or aptamer, an anti-complement Clq monoclonal antibody or aptamer, an anti-complement Cls monoclonal antibody or aptamer, an anti-complement C2 monoclonal antibody or aptamer, an anti-complement C2a monoclonal antibody or aptamer, an anti-complement C2b monoclonal antibody or aptamer, an anti-complement C3 monoclonal antibody or aptamer, an anti-complement C3a monoclonal antibody or aptamer, an anti-complement C3b monoclonal antibody or aptamer, an anti-complement C4 monoclonal antibody or aptamer, an anti-complement C4a monoclonal antibody or aptamer, an anti-complement C4b monoclonal antibody or aptamer, an anti-complement C5 monoclonal antibody or aptamer, an anti-complement C5a monoclonal antibody or aptamer, an anti-complement C5b monoclonal antibody or aptamer, an anti-complement C6 monoclonal antibody or aptamer, an anti-complement C7 monoclonal antibody or aptamer, an anti-complement C8 monoclonal antibody or aptamer, or an anti-complement C9 monoclonal antibody or aptamer, or preferably an anti-complement C5 antibody; (41) angiotensin I converting enzyme (ACE); (42) interleukin 10 (IL10); (43) an anti-TNF monoclonal antibody; (43) Rab chaperone 1 (CHM); (44) retinoschisin (RS1); (45) Bardet-Biedl syndrome 1 (BBS1); (46) Bardet-Biedl syndrome 2 (BBS2); (47) ADP ribosylation factor-like GTPase 6 (ARL6); (48) Bardet-Biedl syndrome 4 (BBS4); (49) Bardet-Biedl syndrome 5 (BBS5); (50) McKusick-Kaufman syndrome (MKKS); (51) Bardet-Biedl syndrome 7 (BBS7); (52) tetratricopeptide repeat domain 8 (TTC8); (53) Bardet-Biedl syndrome 9 (BBS9); (54) Bardet-Biedl syndrome 10 (BBS10);(55) tripartite motif-containing 32 (TRIM32); (56) Bardet-Biedl syndrome 12 (BBS12); (57) MKS transition zone complex subunit 1 (MKS1); (58) WD repeat-containing planar cell polarity effector (WDPCP); (59) serologically defined colon cancer antigen 8 (SDCCAG8); (6) leucine zipper transcription factor-like 1 (LZTFL1); (61) BBSome interacting protein 1 (BBIP1); (62) intraflagellar transport protein 27 (IFT27); (63) guanylate cyclase activator 1A (GUCA1A); (64) OPA1 mitochondrial motor protein-like GTPase (OPA1); (65) RP1 axon microtubule associated (RP1); (66) RP2 activator of ARL3 GTPase (RP2); (67) peripherin 2 (PRPH2); (68) pre-mRNA processing factor 31 (PRPF31); (69) pre-mRNA processing factor 8 (PRPF8); (70) eyes shut homolog (EYS); (71) FAM161 centrosomal protein A (FAM161A); (72) nuclear receptor subfamily 2, group E, member 3 (NR2E3); (73) MER proto-oncogene tyrosine kinase (MERTK); (74) phosphodiesterase 6B (PDE6B); (75) prominin 1 (PROM1); (76) phosphodiesterase 6A (PDE6A); (77) interphotoreceptor matrix proteoglycan 2 (IMPG2); (78) male germ cell-associated kinase (MAK); (79) intraflagellar transport protein 140 (IFT140); (80) anti- membrane attack complex (MAC) monoclonal antibody; (81) HtrA serine peptidase 1 (HTRA1); (82) bestrophin 1 (BEST1); (83) complement factor B antisense oligonucleotide; (84) anti-beta-amyloid monoclonal antibody; (85) CD59 glycoprotein (CD59); (86) channelrhodopsin-1 (ChR1); (87) channelrhodopsin-2 (ChR2); (88) anti-complement factor C5a aptamer or monoclonal antibody; (89) anti-complement factor D monoclonal antibody or aptamer; (90) DnaJ heat shock protein family (Hsp40) member C3 (DNAJC3); (91) beta-2 adrenergic receptor siRNA; (92) caspase-2 (CASP2); (93) insulin receptor substrate 1 (IRS1); (94) HIF-1 response protein RTP801 (RTP801); (95) transforming growth factor beta 2 (TGFB2); (96) brain-derived neurotrophic factor (BDNF); (97) ciliary neurotrophic factor (CNTF); (98) prostaglandin endoperoxide synthase 2 (PTGS2);(99) Prostaglandin F receptor (PTGFR); (100) Hyaluronidase; (101) Pigment epithelium-derived factor (PEDF); (102) Vascular endothelial growth factor (VEGF); (103) Placental growth factor (PGF); (104) Myocilin (MYOC); (105) C-C motif chemokine receptor 5 (CCR5) siRNA; (106) Anti-CD19 monoclonal antibody or aptamer; (107) Crumbs cell polarity complex component 2 (CRB2); (108) Histone deacetylase 4 (HDAC4); (109) Rhodopsin (RHO); (110) Nerve growth factor (NGF); (111) Nuclear factor erythroid 2-like 2 (NRF2); (112) Glutathione S-transferase pi 1 (GSTP1); (113) Rod-derived cone viability factor (RDCVF); (114) Retinal dehydrogenase binding protein 1 (RLBP1); (115) Double homeobox 4 (DUX4); (116) NLR family pyrin domain containing 3 (NLRP3); (117) Spleen associated tyrosine kinase (SYK); (118) Adrenocorticotropic hormone (ACTH); (119) Anti-CD59 monoclonal antibody or aptamer; (120) Notch regulated ankyrin repeat protein (NRARP); (121) Alpha-2-antiplasmin (A2AP); (122) Plasminogen (PLG); (123) Growth hormone; (124) Insulin-like growth factor 1 (IGF1); (125) Interleukin 1 beta (IL1B); (126) Angiotensin I converting enzyme 2 (ACE2); (127) Anti-integrin oligopeptide; (128) Anti-placental growth factor (PGF) monoclonal antibody or aptamer; (129) Anti-insulin-like growth factor 1 receptor (IGF1R) monoclonal antibody or aptamer; (130) Anti-insulin-like growth factor 2 receptor (IGF2R) monoclonal antibody or aptamer; (131) RTP801 siRNA; (132) Matrix metalloproteinase 2 (MMP2) RNAi; (133) G protein-coupled receptor 143 (GPR143); (134) Tyrosinase (TYR); (135) Anti-leucine-rich repeat and Ig domain-containing protein 1 (LINGO1) monoclonal antibody or aptamer; (136) Retinitis pigmentosa GTPase regulator (RPGR); (137) Cyclic nucleotide-gated channel beta 3 (CNGB3); (138) Cyclic nucleotide-gated channel alpha 3 (CNGA3); (139) Retinoid isomerohydrolase RPE65 (RPE65); (14) Anti-TNF-alpha (TNF) monoclonal antibody; or (140) Interleukin 10 (IL10).

[1108] In certain embodiments of the methods described herein, (1) the ocular condition is associated with Batten-CLN1 and the therapeutic product is palmitoyl-protein thioesterase 1 (PPT1); (2) the ocular condition is associated with Batten-CLN2 and the therapeutic product is tripeptidyl- peptidase 1 (TPP1); (3) the ocular condition is associated with Batten-CLN3 and the therapeutic product is Battenin (CLN3); (4) the ocular condition is associated with Batten-CLN6 and the therapeutic product is CLN6 transmembrane ER protein (CLN6); (5) the ocular condition is associated with Batten-CLN7 and the therapeutic product is major facilitator superfamily domain containing 8 (MFSD8); (6) the ocular condition is associated with Usher Syndrome Type 1 and the therapeutic product is myosin VIIA (MY07A); (7) the ocular condition is associated with Usher Syndrome Type 1 and the therapeutic product is cadherin-related 23 (CDH23); (8) the ocular condition is associated with Usher Syndrome Type 2 and the therapeutic product is protocadherin-related 15 (PCDH15); (9) the ocular condition is associated with Usher Syndrome Type 2 and the therapeutic product is Usherin (USH2A); (10) the ocular condition is associated with Usher Syndrome Type 3 and the therapeutic product is Clarin 1 (CLRN1); (11) the ocular condition is associated with Stargardt Disease and the therapeutic product is ATP binding cassette subfamily A member 4 (ABCA4); (12) the ocular condition is associated with Stargardt Disease and the therapeutic product is ELOVL fatty acid elongase 4 (ELOVL4); (13) the ocular condition is associated with uveitis and the therapeutic product is an anti- interleukin 6 (IL6) monoclonal antibody; (14) the ocular condition is associated with uveitis and the therapeutic product is an anti-TNF-a (TNF) monoclonal antibody; (15) the ocular condition is associated with diabetic macular edema (DME) and the therapeutic product is an anti-IL6 monoclonal antibody; (16) the ocular condition is associated with red-green color blindness and the therapeutic product is L opsin (OPN1LW); (17) the ocular condition is associated with red-green color blindness and the therapeutic product is M opsin (OPN1MW); (18) the ocular condition is associated with blue cone monochromacy and the therapeutic product is M opsin (OPN1MW); (19) the ocular condition is associated with Leber Congenital Amaurosis 1 (LCA 1) and the therapeutic product is retinal guanylate cyclase 2D (GUCY2D); (20) the ocular condition is associated with Leber Congenital Amaurosis 2 (LCA 2) and the therapeutic product is retinoid isomerohydrolase RPE65 (RPE65); (21) the ocular condition is associated with LCA 3 and the therapeutic product is spermatogenesis associated 7 (SPATA7); (22) the ocular condition is associated with Leber Congenital Amaurosis 4 (LCA 4) and the therapeutic product is aryl hydrocarbon receptor interacting protein-like 1 (AIPL1);(23) the eye condition is associated with Leber congenital amaurosis 5 (LCA 5) and the therapeutic product is Lebercilin (LCA5); (24) the eye condition is associated with Leber congenital amaurosis 6 (LCA 6) and the therapeutic product is RPGR interacting protein 1 (RPGRIP1); (25) the eye condition is associated with Leber congenital amaurosis 7 (LCA 7) and the therapeutic product is cone-rod homeobox (CRX); (26) the eye condition is associated with Leber congenital amaurosis 8 (LCA 8) and the therapeutic product is Crumbs cell polarity complex component 1 (CRB1) (also known as LCA8); (27) the eye condition is associated with Leber congenital amaurosis 9 (LCA 9) and the therapeutic product is nicotinamide nucleotide adenylyltransferase 1 (NMNAT1); (28) the eye condition is associated with Leber congenital amaurosis 10 (LCA 10) and the therapeutic product is centrosomal protein 290 (CEP290); (29) the eye condition is associated with Leber congenital amaurosis 11 (LCA 11) and the therapeutic product is inosine monophosphate dehydrogenase 1 (IMPDH1); (30) the eye condition is associated with Leber congenital amaurosis 12 (LCA 12) and the therapeutic product is retinal degeneration 3, GUCY2D regulator (RD3); (31) the eye condition is associated with Leber congenital amaurosis 13 (LCA 13) and the therapeutic product is retinol dehydrogenase 12 (RDH12); (32) the eye condition is associated with Leber congenital amaurosis 14 (LCA 14) and the therapeutic product is lecithin retinol acyltransferase (LRAT); (33) the eye condition is associated with Leber congenital amaurosis 15 (LCA 15) and the therapeutic product is tubby-like protein 1 (TULP1); (34) the eye condition is associated with Le...

Claims

1. A method of subretinal administration for treating an ocular condition without vitrectomy, comprising administering to the subretinal space of an eye of a human subject in need of treatment a recombinant viral vector comprising a nucleotide sequence encoding a therapeutic product, such that the therapeutic product is expressed and the ocular condition is treated, wherein the method does not include performing a vitrectomy on the eye of the human patient.

2. The method of claim 1, wherein the administering step comprises administering the recombinant viral vector therapeutic product to the subretinal space of the eye of the human subject via the suprachoroidal space of the eye of the human subject.

3. The method of claim 2, wherein the administering step is by using a subretinal drug delivery device comprising a catheter that is insertable through and towards the posterior pole of the suprachoroidal space, a small needle tip for injection into the subretinal space at the posterior pole.

4. The method of claim 3, wherein the administering step comprises inserting the catheter of the subretinal drug delivery device through the suprachoroidal space.

5. A method of suprachoroidal administration for treating an ocular condition, comprising administering to the suprachoroidal space of an eye of a human subject in need of treatment a recombinant viral vector comprising a nucleotide sequence encoding a therapeutic product, such that the therapeutic product is expressed and the ocular condition is treated.

6. The method of claim 5, wherein the administering step is by using a suprachoroidal drug delivery device to inject the recombinant viral vector into the suprachoroidal space.

7. The method of claim 5 or 6, wherein the suprachoroidal drug delivery device is a microinjector.

8. A method of juxtascleral administration for treating an ocular condition, comprising administering to the juxtascleral surface of an eye of a human subject in need of treatment a recombinant viral vector comprising a nucleotide sequence encoding a therapeutic product, such that the therapeutic product is expressed and the ocular condition is treated.

9. The method of claim 8, wherein the administering step is by using a juxtascleral drug delivery device comprising a cannula with a tip that is insertable and held in direct apposition to the scleral surface.

10. The method of claim 9, wherein the administering step comprises inserting the tip of the cannula in direct apposition to the scleral surface.

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