Gene therapy for eye pathologies

Abstract

To provide methods for the delivery of therapeutic products to the retina / vitreal humour in the eyes of human subjects.SOLUTION: A method of subretinal administration without vitrectomy for treating a pathology of the eye, comprises 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, expressing the therapeutic product to result in treatment of the pathology of the eye, wherein the method does not comprise performing a vitrectomy on the eye of the human patient.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] 1. CROSS-REFERENCE TO RELATED APPLICATIONS This application is a continuation of U.S. Provisional Patent Application No. 62 / 828,949, filed April 3, 2019. , No. 62 / 856,533 filed June 3, 2019, and December 2019 This application claims priority from application No. 62 / 946,158 filed on the 10th. is incorporated herein by reference in its entirety.

[0002] Reference to electronically submitted sequence listing This application is filed under "12656-126-228_Sequence_Listing.tx It was named "t" and was made on March 24, 2020, measuring 2,025,574 By reference to the Sequence Listing submitted with this application as a text file, Incorporate.

[0003] 2. Introduction For example, recombinant viral vectors such as recombinant adeno-associated viral (rAAV) vectors into the retina / vitreous humor of the eye of a human subject to treat an ocular condition, including For example, therapeutic proteins (e.g., antibodies), therapeutic RNAs (e.g., shRNA, siR Described are compositions and methods for delivery of therapeutic aptamers (RNAs, miRNAs, and therapeutic aptamers). do. [Background technology]

[0004] 3.Background technology The human eye is a highly complex and highly developed sensory organ that is responsible for many diseases and disorders. Approximately 285 million people worldwide are visually impaired, of which 39 million are blind and 246 million people have moderate to severe visual impairment (World Health Organization,2012,“Global Data On Visual Impairments 2010,”Geneva:World H The main causes of blindness are cataracts (47%), glaucoma (48%), and glaucoma. Cataracts (12%), age-related macular degeneration (AMD) (9%), and diabetic retinopathy (5%) (World Health Organization,2007,“Global Initiative For The Elimination Of Avoida ble Blindness:Action Plan 2006-2011,”Gen eva:World Health Organization).

[0005] A vast number of eye diseases and conditions associated with ocular pathology are caused by genetic modifications or protein regulation. This may be due to a lack of proper control (Stone et al., 2017, Ophthalmolog y 124(9):1314-1331). Recent advances in genomics and proteomics These advances may contribute to the understanding of the underlying disease mechanisms and / or genetic basis of such ocular diseases or conditions. Gene therapy has had a major impact on the treatment of certain eye diseases. (See, for example, International Patent Application No. PCT / US2017 / 027650 (International Publication No. W See O2017 / 181021 A1).

[0006] Therapies that specifically address underlying genetic abnormalities to treat ocular conditions are well documented. There is a significant unmet medical need. Summary of the Invention

[0007] 4. Summary of the Invention For example, recombinant viral vectors such as recombinant adeno-associated viral (rAAV) vectors into the retina / vitreous humor of the eye of a human subject to treat an ocular condition, including For example, therapeutic proteins (e.g., antibodies), therapeutic RNAs (e.g., shRNA, siR Described are compositions and methods for delivery of therapeutic aptamers (RNAs, miRNAs, and therapeutic aptamers). Therapeutic products include, for example, therapeutic proteins (e.g., antibodies), therapeutic RNA (e.g., (e.g., shRNA, siRNA, and miRNA), or therapeutic aptamers. In certain embodiments, the therapeutic product is a human protein or a polypeptide that binds to a human protein. Antibodies include monoclonal antibodies, polyclonal antibodies, and recombinantly produced antibodies. , human antibodies, humanized antibodies, chimeric antibodies, synthetic antibodies, two heavy chain molecules and two light chain molecules tetrameric antibodies, including antibody light chain monomers, antibody heavy chain monomers, antibody light chain dimers, and antibody heavy chain dimers antibody, antibody light chain-heavy chain pair, intrabody, heteroconjugate antibody, monovalent antibody, whole antibody Antibody fragments include, but are not limited to, antigen-binding fragments of full-length antibodies, as well as fusion proteins of the above. Such antigen-binding fragments include single domain antibodies (heavy chain antibodies (VH H) or variable domains of nanobodies), Fab, F(ab')2, and scFv (single stranded Fv) In certain embodiments, the therapeutic agent may be a nucleotide or a nucleotide sequence. Therapeutic products (e.g., therapeutic proteins) are post-translationally modified. Post-translational modifications are those that allow a therapeutic product (e.g., a therapeutic protein) to progress through a particular pathway as described herein. Therapeutic products (e.g., post-translationally modified therapeutics) are specific to the cell type to which they are delivered. The delivery is performed in a manner similar to that described for gene therapy, creating a permanent depot that provides a continuous supply of the therapeutic product within the eye. For example, recombinant viral vectors or recombinant DNA vectors encoding therapeutic products can be used. A. Expression constructs (collectively, "recombinant vectors") are introduced into the eye(s) of a human patient. Suprachoroidal space, subretinal space (with or without vitrectomy (e.g., catheterization) through the suprachoroidal space or via a perichoroidal injection), the intraretinal space, and / or the sclera This can be achieved by administration to the outer surface (ie, juxtascleral administration).

[0008] In one aspect, a method of subretinal administration without vitrectomy for treating an ocular condition is disclosed herein. The method provides for administering a therapeutic product to the subretinal space of the eye of a human subject in need of treatment. A recombinant viral vector containing a nucleotide sequence encoding the therapeutic product is administered to express the therapeutic product. and subjecting the eye of the human patient to a vitrectomy to provide treatment for the ocular condition. In certain embodiments, the administering step does not include administering to the retina of the eye of said human subject. and administering a recombinant viral vector therapeutic product to the subchoroidal space via the suprachoroidal space of the human subject's eye. In certain embodiments, the administering step includes administering a drug to a patient. A catheter that can be passed through the epiretinal space toward the posterior pole and injects a fine needle into the subretinal space at the posterior pole. In certain embodiments, administration is by use of a subretinal drug delivery device comprising: The steps include inserting a catheter of a subretinal drug delivery device into the suprachoroidal space and This includes passing through a cavity.

[0009] In another aspect, provided herein is a method for treating an ocular condition, the method comprising: a nucleotide sequence encoding a therapeutic product into the subretinal space of the eye of a human subject in need thereof. Administering a recombinant viral vector to express a therapeutic product and provide treatment for an ocular condition and wherein the method does not include performing a vitrectomy on the eye of the human patient. In some embodiments, the administering step comprises administering a retinal or retinal composition to the subretinal space of the eye of the human subject, or to the choroid of the eye of the human subject. This involves administering a recombinant viral vector therapeutic product via the epithelial space. In some embodiments, the administration step involves inserting the catheter into the suprachoroidal space and passing it through the suprachoroidal space toward the posterior pole. and a catheter for injecting a fine needle into the subretinal space at the posterior pole. In certain embodiments, the administering step is by use of a subretinal drug delivery device. The method includes inserting a catheter into the suprachoroidal space and passing the catheter through the suprachoroidal space.

[0010] In one aspect, a method of subretinal administration in conjunction with vitrectomy to treat an ocular condition is described herein. The method includes delivering a therapeutic product to the subretinal space of the eye of a human subject in need of treatment. A recombinant viral vector containing a nucleotide sequence for expression of a therapeutic product is administered. and providing treatment for an ocular condition, the method comprising performing a vitrectomy on the eye of the human patient. In certain embodiments, the vitrectomy is a partial vitrectomy.

[0011] In another aspect, provided herein is a method for treating an ocular condition, the method comprising: a nucleotide sequence encoding a therapeutic product into the subretinal space of the eye of a human subject in need thereof. Administering a recombinant viral vector to express a therapeutic product and provide treatment for an ocular condition and the method includes performing a vitrectomy on the eye of the human patient. In an embodiment, the vitrectomy is a partial vitrectomy.

[0012] In one aspect, provided herein is a method of suprachoroidal administration for treating an ocular condition, the method comprising: The method comprises delivering a nucleoside encoding a therapeutic product into the suprachoroidal space of the eye of a human subject in need of treatment. and administering a recombinant viral vector containing the nucleotide sequence to express a therapeutic product to treat the ocular condition. In certain embodiments, the administering step comprises administering a recombinant viral vector to the host. by injecting the agent into the suprachoroidal space using a suprachoroidal drug delivery device. In certain embodiments, the suprachoroidal drug delivery device is a microinjector. is.

[0013] In another aspect, provided herein is a method for treating an ocular condition, the method comprising: a nucleotide sequence encoding a therapeutic product in the suprachoroidal space of the eye of a human subject in need thereof; and administering a recombinant viral vector containing the compound to express a therapeutic product to provide treatment for the ocular condition. In certain embodiments, the administering step comprises administering the recombinant viral vector to a mammalian cell in a mammalian cell line. by injection 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 or suprachoroidal space is achieved by methods described in International Publication No. WO20 16 / 042162, WO2017 / 046358, WO2017 / 158365, and WO2017 / 158366 (each of which is incorporated herein by reference in its entirety). This can be done using the methods and / or devices described and disclosed in

[0015] In one aspect, provided herein is a method of administration to the extrascleral space to treat an ocular condition. The method includes delivering a therapeutic product to the outer surface of the sclera of the eye of a human subject in need of treatment. A recombinant viral vector containing a nucleotide sequence for expression of a therapeutic product is administered. In certain embodiments, the administering step includes administering a cannula The tip of the cannula can be inserted into the scleral surface and placed directly in apposition to the scleral surface. In certain embodiments, the administration step involves the use of a juxtascleral drug delivery device. The procedure involves inserting the tip of the cannula into the scleral surface and placing it directly in apposition to the scleral surface. include.

[0016] In another aspect, provided herein is a method for treating an ocular condition, the method comprising: a nucleotide sequence encoding a therapeutic product on the outer surface of the sclera of the eye of a human subject in need thereof; and administering a recombinant viral vector containing the compound to express a therapeutic product to treat an ocular condition. In certain embodiments, the administering step includes applying the tip of the cannula to the scleral surface. a juxtascleral drug delivery device that includes a cannula that can be inserted into the sclera and placed directly in apposition to the scleral surface; In certain embodiments, the administering step is by use of a device. This includes inserting the end into the scleral surface and directly apposing it to the scleral surface.

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

[0018] In certain embodiments, the ocular condition is neovascular age-related macular degeneration (nAMD) ("weeping macular degeneration"). Also known as "exudative" and neovascular AMD ("WAMD" or "wet AMD") (not related to the

[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. It is the body.

[0022] In one aspect, a method of subretinal administration in conjunction with vitrectomy to treat an ocular condition is described herein. The method includes delivering a therapeutic product to the subretinal space of the eye of a human subject in need of treatment. A recombinant viral vector containing a nucleotide sequence for expression of a therapeutic product is administered. and providing treatment for an ocular condition, the method comprising performing a vitrectomy on the eye of the human patient. 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.

[0023] In another aspect, provided herein is a method for treating an ocular condition, the method comprising: a nucleotide sequence encoding a therapeutic product into the subretinal space of the eye of a human subject in need thereof. Administering a recombinant viral vector to express a therapeutic product and provide treatment for an ocular condition the method includes performing a vitrectomy on the eye of the human patient, and the therapeutic product is In certain embodiments, the antibody is an anti-human vascular endothelial growth factor (hVEGF) antibody. The condition is an ocular disease or a disease involving multiple organs including the eye. The vitrectomy is a partial vitrectomy.

[0024] In one aspect, provided herein is a method of subretinal administration for treating an ocular condition, the method comprising: The method comprises administering to a human subject in need of treatment a laser beam to the optic disc, fovea, and macula located in the posterior segment of the eye. A recombinant viral vector containing a nucleotide sequence encoding a therapeutic product is delivered to the subretinal space. and administering to the subject a therapeutic product to effect treatment of the ocular condition, the method comprising: In certain embodiments, the injection step does not include performing a vitrectomy on the eye of the human patient. is by intravitreal injection. In certain embodiments, the method of intravitreal administration comprises: Provide uniform expression of the therapeutic product throughout the eye (e.g., expression levels at the injection site) The variation in expression levels was 5%, 10%, 20%, 30%, and 40% compared to expression levels in other regions of the eye. %, or less than 50%). In certain embodiments, the transvitreal injection is performed on the superior or inferior side of the eye. The needle is inserted into the sclera through the inferior side of the eye, and the needle is passed completely through the vitreous body to inject the recombinant virus. In certain embodiments, the needle includes: In certain embodiments, the intravitreal injection is performed using a cannula. A needle is inserted into the sclera, a cannula is inserted into the trocar, and the recombinant virus is injected through the vitreous body. In certain embodiments, the therapeutic vector is injected into the subretinal space on the opposite side. In certain embodiments, the anti-hVEGF antibody is an anti-hVEGF antibody. In certain embodiments, the anti-hVEGF antigen-binding fragment is an EGF antigen-binding fragment. The fragments are Fab, F(ab')2, or single-chain variable fragments (scFv). In certain embodiments, the anti-hVEGF antibody is selected from the group consisting of the antibody of SEQ ID NO: 2 or SEQ ID NO: 4. a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 3, and a light chain comprising the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 3. In certain embodiments, the anti-hVEGF antibody comprises the light chain CDRs of SEQ ID NOs: 14-16. 1 to 3 and heavy chain CDR1 of SEQ ID NOs: 17 to 19 or SEQ ID NOs: 20, 18, and 21 In certain embodiments, the ocular condition is nAMD, dry age-related macular degeneration. (dry AMD), retinal vein occlusion (RVO), diabetic macular edema (DME), or diabetes In certain embodiments, the ocular condition is associated with diabetic retinopathy (DR). To connect.

[0025] In another aspect, provided herein is a method for treating an ocular condition, the method comprising: In the subretinal space around the optic disc, fovea, and macula located in the posterior segment of the eye of a human subject in need thereof. administering a recombinant viral vector containing a nucleotide sequence encoding a therapeutic product, and expressing a therapeutic product to provide treatment for the ocular condition, the method comprising administering to the human patient In certain embodiments, the injection step does not include performing a vitrectomy on the eye. In certain embodiments, the method of intravitreal administration is by intraocular injection. This results in uniform expression of the therapeutic product (e.g., variations in expression levels at the injection site, 5%, 10%, 20%, 30%, 40%, or In certain embodiments, the transvitreal injection is performed on the superior or inferior side of the eye. A sharp needle is inserted into the sclera through the vitreous body, and the sharp needle is passed completely through the vitreous body to deliver the recombinant viral vector. into the contralateral subretinal space. In certain embodiments, the needle is at 2 o'clock or In certain embodiments, the transvitreal injection is performed by inserting the trocar into the sclera. The cannula is inserted into the vitreous body, and the recombinant viral vector is delivered through the vitreous body. In certain embodiments, the therapeutic product comprises an anti-histamine. In certain embodiments, the anti-hVEGF antibody is an anti-hVEGF antibody. In certain embodiments, the anti-hVEGF antigen-binding fragment is an anti-hVEGF antigen-binding fragment. The fragment may be a Fab, F(ab')2, or a single chain variable fragment (scFv). In certain embodiments, the anti-hVEGF antibody has 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, the anti-hVEGF antibody comprises light chain CDRs 1-3 of SEQ ID NOs: 14-16. and heavy chain CDRs 1 to 3 of SEQ ID NOs: 17 to 19 or SEQ ID NOs: 20, 18, and 21. In certain embodiments, the ocular condition is nAMD, dry age-related macular degeneration (nAMD). MD), retinal vein occlusion (RVO), diabetic macular edema (DME), or diabetic retinal In certain embodiments, the ocular condition is associated with nAMD.

[0026] In certain embodiments of the methods described herein, (1) the ocular condition is a condition determined by the Batten-CL method. Related to N1, the therapeutic product is palmitoyl-protein thioesterase 1 (PPT1 (2) the ocular pathology is associated with Batten-CLN2 and the therapeutic product is a tripeptide (3) Ocular pathology is related to Batten-CLN3. The therapeutic product is Battenin (CLN3); (4) the eye condition is Batten-C Related to LN6, therapeutic products include the CLN6 transmembrane ER protein (CLN6); (5) ophthalmic The pathology is associated with Batten-CLN7, and therapeutic products target the key facilitator superfamily (6) The eye pathology is Usher syndrome. Associated with group 1, the therapeutic product is myosin VIIA (MYO7A); (7) eye disease The condition is associated with Usher syndrome type 1, and the therapeutic product is a cadherin-related 23 (CDH23 (8) The eye condition is associated with Usher syndrome type 2, and the therapeutic product is protocalcin. PCDH15 (Protein-Coated Hemoglobin Dependent Hormone 15); (9) Ocular pathology is associated with Usher syndrome type 2. A related therapeutic product is ascherin (USH2A); (10) eye conditions are Associated with Sher syndrome type 3, the therapeutic product is Clarrin 1 (CLRN1); (11 The eye condition is related to Stargardt's disease, and the therapeutic product is an ATP-binding cassette subunit. (12) Ocular pathology is related to Stargardt disease. In this connection, the therapeutic product is ELOVL fatty acid elongase 4 (ELOVL4); (13 The eye condition is related to uveitis, and the therapeutic product is an anti-interleukin 6 (IL6) molecule. (14) The ocular condition is associated with uveitis, and the therapeutic product is an anti- TNF alpha (TNF) monoclonal antibody; (15) eye pathology, diabetic jaundice, In relation to plaque edema (DME), 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 monochromatism, and the therapeutic product is a phosphodiesterase inhibitor (M opsin (O (19) The eye pathology is related to Leber congenital amaurosis-1 (LCA 1). The therapeutic product is guanylate cyclase 2D, retinal (GUCY2D); (20) The eye condition is associated with Leber congenital amaurosis-2 (LCA-2), and the therapeutic product is Retinoid isomerohydrolase RPE65 (RPE65); (21) Ocular pathology , LCA 3-related, and the therapeutic product is spermatogenesis-associated 7 (SPATA7); (22 The eye condition is associated with Leber congenital amaurosis-4 (LCA-4), and therapeutic products are alpha-hydrocarbon receptor-interacting protein-like 1 (AIPL1); (23) ocular pathology It is associated with Leber congenital amaurosis-5 (LCA 5) and the therapeutic product is Reversillin (LCA 5); (24) The eye condition is related to Leber congenital amaurosis-6 (LCA-6) and is treatable. The therapeutic product is RPGR-interacting protein 1 (RPGRIP1); (25) eye disease The condition is associated with Leber congenital amaurosis-7 (LCA 7), and the therapeutic product is a cone-rod (26) The eye condition is Leber congenital amaurosis-8 (LC A8), the therapeutic product is Crumbs cell polarity complex component 1 (CRB1). (27) The eye condition is Leber congenital amaurosis-9 (LCA-9). A 9) and the therapeutic product is a nicotinamide nucleotide adenylyltransferase. (28) The eye condition is Leber congenital amaurosis-10 (L CA 10) and the therapeutic product is centrosomal protein 290 (CEP290) (29) The eye condition is related to Leber congenital amaurosis-11 (LCA 11), and therapeutic products The substance is inosine monophosphate dehydrogenase 1 (IMPDH1); (30) Ocular pathology is associated with Leber congenital amaurosis-12 (LCA 12), and therapeutic products are used to treat retinal degeneration 3, GUCY2D regulator (RD3); (31) eye pathology Leber congenital amaurosis-1 3 (LCA 13), and the therapeutic product inhibits retinol dehydrogenase 12 (RDH 12); (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 therapeutic products is tabby-like protein 1 (TULP1); (34) the eye condition is Leber congenital anomaly Related to LCA-16 (LCA 16), the therapeutic product inhibits potassium voltage-gated channel subunits. Family J member 13 (KCNJ13); (35) eye pathology is Leber inherited The therapeutic product is a mitochondrially encoded NADPH receptor agonist (NAD) inhibitor associated with leukemia-related optic neuropathy (LHON). H dehydrogenase 1 (MT-ND1); (36) ocular pathology associated with LHON , the therapeutic product is mitochondrially encoded NADH dehydrogenase 4 (MT-N D4); (37) The ocular pathology is associated with LHON, and the therapeutic product is a mitochondrial NADH dehydrogenase 6 (MT-ND6) encoded by (38) ocular pathology is associated with neuromyelitis optica (NMO), and the therapeutic product is an anti-complement antibody or anti-complement aptamer. and the anti-complement monoclonal antibody or aptamer is an anti-complement C1 antibody or aptamer. aptamer, anti-complement C1q monoclonal antibody or aptamer, anti-complement C1s monoclonal monoclonal antibody or aptamer, anti-complement C2 monoclonal antibody or aptamer, anti-complement Anti-complement C2a monoclonal antibody or aptamer, anti-complement C2b monoclonal antibody or or aptamer, anti-complement C3 monoclonal antibody or aptamer, anti-complement C3a monoclonal antibody Clonal antibody or aptamer, anti-complement C3b monoclonal antibody or aptamer -, anti-complement C4 monoclonal antibody or aptamer, anti-complement C4a monoclonal antibody Anti-complement C4b monoclonal antibody or aptamer, anti-complement C 5 monoclonal antibody or aptamer, anti-complement C5a monoclonal antibody or aptamer aptamer, anti-complement C5b monoclonal antibody or aptamer, anti-complement C6 monoclonal antibody monoclonal antibody or aptamer, anti-complement C7 monoclonal antibody or aptamer, anti-complement Anti-complement C8 monoclonal antibody or aptamer, or anti-complement C9 monoclonal antibody or an aptamer, or preferably an anti-complement C5 antibody; (39) the ocular pathology is N In relation to MO, the therapeutic product is an anti-IL6 monoclonal antibody or aptamer; 40) The ocular condition is related to uveitis, and the therapeutic product is an anti-complement monoclonal antibody or is an aptamer, and the anti-complement monoclonal antibody or aptamer is an anti-complement C1 monoclonal antibody. monoclonal antibody or aptamer, anti-complement C1q monoclonal antibody or aptamer , anti-complement C1s monoclonal antibody or aptamer, anti-complement C2 monoclonal antibody or aptamer, anti-complement C2a monoclonal antibody or aptamer, anti-complement C2 b Monoclonal antibody or aptamer, anti-complement C3 monoclonal antibody or aptamer aptamer, anti-complement C3a monoclonal antibody or aptamer, anti-complement C3b monoclonal antibody monoclonal antibody or aptamer, anti-complement C4 monoclonal antibody or aptamer, anti-complement Anti-complement C4a monoclonal antibody or aptamer, anti-complement C4b monoclonal antibody or or aptamer, anti-complement C5 monoclonal antibody or aptamer, anti-complement C5a monoclonal antibody Clonal antibody or aptamer, anti-complement C5b monoclonal antibody or aptamer -, anti-complement C6 monoclonal antibody or aptamer, anti-complement C7 monoclonal antibody or aptamer, anti-complement C8 monoclonal antibody or aptamer, or anti-complement C9 monoclonal antibody or aptamer, or preferably an anti-complement C5 antibody (41) The eye condition is related to uveitis, and the therapeutic product is angiotensin I converting enzyme (AEC). (42) The eye condition is related to uveitis, and the therapeutic product is an interferon. IL-10 (IL-10); (43) eye conditions related to uveitis and therapeutic The product is an anti-TNF monoclonal antibody; (44) the ocular pathology is related to choroideremia. In this connection, the therapeutic product is Love Escort Protein 1 (CHM); (45) Ocular pathology is associated with X-linked retinoschisis (XLRS), and the therapeutic product is retinoschisin (RS1) (46) The eye condition is associated with Bardet-Biedl syndrome, and the therapeutic product is Bardet-Biedl syndrome 1 (BBS1); (47) the eye condition is Bardet-Biedl syndrome Related to group 2, the therapeutic product is Bardet-Biedl syndrome 2 (BBS2); (48) The ocular condition is associated with Bardet-Biedl syndrome 3 and the therapeutic product is an ADP-ribosylation factor -like GTPase 6 (ARL6) (also known as BBS3); (49) ocular pathology is associated with Bardet-Biedl syndrome 4, and the therapeutic product is intended to treat Bardet-Biedl syndrome 4 (B BS4); (50) eye pathology associated with Bardet-Biedl syndrome5, therapeutic product is Bardet-Biedl syndrome 5 (BBS5); (51) the ocular pathology is Bardet-Biedl syndrome Related to dollar syndrome 6, therapeutic products are McKusick-Kaufman syndrome (MKKS) (52) The eye condition is Bardet-Biedl syndrome. Related to group 7, the therapeutic product is Bardet-Biedl syndrome 7 (BBS7); (53) The ocular condition is associated with Bardet-Biedl syndrome, and the therapeutic product is tetratricopeptide. repeat domain 8 (TTC8), also known as BBS8; (54) The condition is associated with Bardet-Biedl syndrome, and the therapeutic product is 9 (BBS9); (55) the ocular condition is associated with Bardet-Biedl syndrome 10 and is treatable. The therapeutic product is Bardet-Biedl syndrome 10 (BBS10); (56) an ocular condition Associated with Bardet-Biedl syndrome,11 the therapeutic product is a tripartite motif-containing32 (TRI M32), also known as BBS11; (57) eye pathology, Related to Bardet-Biedl syndrome 12, the therapeutic product is Bardet-Biedl syndrome 12 (BBS12) (58) The eye condition is associated with Bardet-Biedl syndrome, and the therapeutic product is M KS transition zone complex subunit 1 (MKS1), which is a B Also known as BS13; (59) an ocular condition associated with Bardet-Biedl syndrome 14 The therapeutic product is centrosomal protein 290 (CEP290), which binds BBS14 and Also known as LCA10; (60) ocular pathology related to Bardet-Biedl syndrome15 In this context, the therapeutic product is a WD repeat-containing planar cell polarity effector (WDPCP). (61) The ocular condition is Bardet-Biedl syndrome. 16, the therapeutic product is serologically defined colon cancer antigen 8 (SDCCAG8). (62) The eye condition is Bardet-Biedl syndrome. Related to Group 17, the therapeutic product is leucine zipper transcription factor-like 1 (LZTFL1). , also known as BBS17; (63) the ocular condition Bardet-Biedl syndrome 1 8, wherein the therapeutic product is BBSome-interacting protein 1 (BBIP1); This is also known as BBS18; (64) the ocular condition is Bardet-Biedl syndrome19 A related therapeutic product is intraflagellar transport 27 (IFT27), which is expressed as BBS19. (65) The eye condition is associated with cone dystrophy, and the therapeutic product is guaiamine. guanosine cyclase activator 1A (GUCA1A); (66) ocular pathology, optic nerve Associated with atrophy, therapeutic products inhibit the activity of OPA1, a mitochondrial dynamin-like GTPase (O P A1); (67) The eye condition is associated with retinitis pigmentosa 1, and the therapeutic product is RP1 Axonemal microtubule-associated (RP1); (68) ocular pathology associated with retinitis pigmentosa 2 and treatment The therapeutic product is the RP2 activator of ARL3 GTPase (RP2); (69) The condition is associated with retinitis pigmentosa7 and the therapeutic product is peripherin 2 (PRPH2). (70) The eye condition is associated with retinitis pigmentosa, and the therapeutic product is a precursor mRNA. Protein processing factor 31 (PRPF31); (71) eye pathology, retinitis pigmentosa 12, wherein the therapeutic product is Crumbs cell polarity complex component 1 (CRB1); It is also known as LCA8; (72) an eye condition associated with retinitis pigmentosa 13, The therapeutic product is pre-mRNA processing factor 8 (PRPF8); (73) ocular The condition is associated with retinitis pigmentosa 25, and the therapeutic product is EyeShut homolog (EYS). (74) The eye condition is associated with retinitis pigmentosa 28, and the therapeutic product is FAM 16. 1 Centrosomal protein A (FAM161A); (75) Ocular pathology: Retinitis pigmentosa 37, the therapeutic product is a nuclear receptor subfamily 2 group E member 3 (NR2 E3); (76) The eye condition is associated with retinitis pigmentosa 38, and the therapeutic product is ME R proto-oncogene tyrosine kinase (MERTK); (77) Ocular pathology Retinitis pigmentosa 40 is associated with the therapeutic product phosphodiesterase 6B (PDE6B) (78) The eye condition is associated with retinitis pigmentosa, and the therapeutic product is prominence. 1 (PROM1); (79) an ocular condition associated with retinitis pigmentosa43, and therapeutic production The substance is phosphodiesterase 6A (PDE6A); (80) eye pathology is retinal pigment epithelium The therapeutic product is interphotoreceptor matrix proteoglycan 2 (IM) associated with degeneration56. PG2); (81) The eye condition is associated with retinitis pigmentosa62, and the therapeutic product is 82) Ocular pathology is associated with retinitis pigmentosa 80. A related therapeutic product is intraflagellar transporter 140 (IFT140); (83) ocular pathologies , associated with dry AMD, and the therapeutic product is an anti-complement monoclonal antibody or anti-complement aptamer. and the anti-complement monoclonal antibody or anti-complement aptamer is an anti-complement C1 monoclonal antibody. anti-complement C1q monoclonal antibody or aptamer; Anti-complement C1s monoclonal antibody or aptamer, anti-complement C2 monoclonal antibody or aptamer, anti-complement C2a monoclonal antibody or aptamer, anti-complement C2b Monoclonal antibody or aptamer, anti-complement C3 monoclonal antibody or aptamer Anti-complement C3a monoclonal antibody or aptamer, anti-complement C3b monoclonal antibody monoclonal antibody or aptamer, anti-complement C4 monoclonal antibody or aptamer, anti-complement C4a monoclonal antibody or aptamer, anti-complement C4b monoclonal antibody or aptamer, anti-complement C5 monoclonal antibody or aptamer, anti-complement C5a monoclonal antibody monoclonal antibody or aptamer, anti-complement C5b monoclonal antibody or aptamer , anti-complement C6 monoclonal antibody or aptamer, anti-complement C7 monoclonal antibody or aptamer, anti-complement C8 monoclonal antibody or aptamer, or anti-complement C 9 monoclonal antibody or aptamer, or preferably an anti-complement C5 antibody; (84) The ocular pathology is associated with dry AMD, and the therapeutic product is the anti-membrane attack complex (MAC). The therapeutic product, preferably an anti-MAC therapeutic product, is an anti-MAC monoclonal antibody. This is a monoclonal antibody against a human protein of the membrane attack complex, which The invasion complex is composed of four complement proteins: C5b (SEQ ID NOs: 314-316), C6 (SEQ ID NOs: 317-319), C7 (SEQ ID NO: 317), C7 (SEQ ID NO: 318), and C8 (SEQ ID NOs: 319-321) (85) The ocular pathology is associated with dry AMD, and the therapeutic product inhibits the HtrA serine peptide. (86) Ocular pathology associated with Best's disease, therapeutic product bestrophin 1 (BEST1); (87) an ocular pathology associated with dry AMD. The therapeutic product is a complement factor B antisense oligonucleotide; (88) eye disease The condition is associated with dry AMD, and the therapeutic product is an anti-beta-amyloid monoclonal antibody. (89) The ocular pathology is associated with dry AMD, and the therapeutic product inhibits the CD59 glycoprotein. (90) The ocular pathology is associated with dry AMD, and the therapeutic product is Channelrhodopsin-1 (ChR1), which contains the human homolog of ChR1; 91) The ocular pathology is associated with dry AMD, and the therapeutic product is channelrhodopsin-2 (C hR2), which contains the human homolog of ChR2; (92) the ocular pathology is dry type A In relation to MD, the therapeutic product is an anti-complement monoclonal antibody or an anti-complement aptamer. , complement monoclonal antibodies or anti-complement aptamers, also anti-complement C1 monoclonal antibodies or aptamer, anti-complement C1q monoclonal antibody or aptamer, anti-complement C1s Monoclonal antibody or aptamer, anti-complement C2 monoclonal antibody or aptamer Anti-complement C2a monoclonal antibody or aptamer, anti-complement C2b monoclonal antibody monoclonal antibody or aptamer, anti-complement C3 monoclonal antibody or aptamer, anti-complement C3a monoclonal antibody or aptamer, anti-complement C3b monoclonal antibody or aptamer, anti-complement C4 monoclonal antibody or aptamer, anti-complement C4a monoclonal antibody monoclonal antibody or aptamer, anti-complement C4b monoclonal antibody or aptamer , anti-complement C5 monoclonal antibody or aptamer, anti-complement C5a monoclonal antibody or aptamer, anti-complement C5b monoclonal antibody or aptamer, anti-complement C6 Monoclonal antibody or aptamer, anti-complement C7 monoclonal antibody or aptamer anti-complement C8 monoclonal antibody or aptamer, or anti-complement C9 monoclonal antibody (93) an ocular antibody or aptamer, or preferably an anti-complement C5 antibody; The condition is associated with dry AMD and the therapeutic product is an anti-complement factor D therapeutic product, These include anti-complement factor D monoclonal antibodies or anti-complement factor D aptamers, (94) Ocular pathologies are associated with age-related retinal ganglion cell (RGC) degeneration. The therapeutic product is a member of the DnaJ heat shock protein family (Hsp40). -C3 (DNAJC3), also known as p58IPK; (95) eye disease The condition is associated with blue-cone monochromatism (BCM), and the therapeutic product is a phosphodiesterase inhibitor of L-opsin (OPN1LW ) (96) The eye condition is related to glaucoma, and the therapeutic product is a beta-2 adrenergic (97) The eye condition is related to glaucoma, and the therapeutic product is a catabolic inhibitor of glaucoma. 98) eye pathology associated with glaucoma, and therapeutic products , insulin receptor substrate 1 (IRS1); (99) eye pathology associated with glaucoma, The therapeutic product is the HIF-1 responsive protein RTP801 (RTP801); 00) The eye condition is related to glaucoma, and the therapeutic product is a transforming growth factor-based 101) The eye condition is associated with glaucoma, and the therapeutic product is 102) Ocular pathology is associated with glaucoma and therapeutic The product is ciliary neurotrophic factor (CNTF); (103) an ocular condition associated with glaucoma The therapeutic product is a prostaglandin-endoperoxide synthase 2 (PTGS2 ) (104) The eye condition is related to glaucoma, and the therapeutic product is a prostaglandin F receptor (PTGFR) (in certain embodiments, when the ocular condition is related to glaucoma, A recombinant viral vector containing a nucleotide sequence encoding a PTGFR is administered to a human subject. and then combined with a recombinant viral vector containing a nucleotide sequence encoding PTGS2. In another specific embodiment, a nucleic acid encoding a PTGFR can be administered in combination with A recombinant viral vector containing a nucleotide sequence encoding the nucleotide sequence of PTGS2 is prepared. (105) The eye condition is related to glaucoma, and the therapeutic The product is a hyaluronidase, e.g., HYAL1, HYAL2, HYAL3, HYAL4 (106) The eye condition is related to glaucoma, and the therapeutic product is a pigment epithelial-derived factor (PEDF); (107) an ocular condition related to glaucoma, and therapeutic products The primary marker is vascular endothelial growth factor (VEGF); (108) an ocular condition associated with glaucoma and a treatment option. The therapeutic product is placental growth factor (PGF), which is used in combination with VEGF. (109) The ocular condition is glaucoma (e.g., congenital glaucoma or juvenile glaucoma) The therapeutic product is myocilin (MYOC); (110) eye conditions are In relation to NMO, the therapeutic product is an anti-complement C5 monoclonal antibody; (111) ocular The pathology is related to NMO, and the therapeutic product is a CC motif chemokine receptor 5 (CCR5 ) siRNA, CCR5 shRNA, siRNA or CCR5 miRNA (preferably (112) Ocular pathology is associated with NMO and therapeutic The product is an anti-CD19 monoclonal antibody; (113) Ocular pathology is caused by rhodopsin abruption. Therapeutic products are associated with retinitis pigmentosa with mutations in channelrhodopsin-1 (ChR1 ), which contains the human homolog of ChR1; (114) Ocular pathologies involve the rhodopsin receptor. The therapeutic product is a compound that inhibits the activity of channelrhodopsin-2 (ChR 2), which contains the human homolog of ChR2; (115) Ocular pathologies include retinal pigment epithelial degeneration (RPE) and retinal pigment epithelial degeneration (RPE). The therapeutic product involved in glaucoma is ciliary neurotrophic factor (CNTF); (116) ophthalmic The condition is associated with autosomal recessive retinitis pigmentosa, and the therapeutic product inhibits the Crumbs cell polarity complex. Coalescence Receptor B1 (CRB1); (117) Ocular pathology is associated with autosomal recessive retinitis pigmentosa. A related therapeutic product is Crumbs cell polarity complex component 2 (CRB2); 8) The eye condition is related to retinitis pigmentosa, and the therapeutic product inhibits histone deacetylase 4. (HDAC4); (119) The ocular condition is associated with retinitis pigmentosa, and the therapeutic product is rhodopsin (RHO); (120) an ocular condition related to retinitis pigmentosa, and treatment The product is nerve growth factor (NGF); (121) the ocular pathology is related to retinitis pigmentosa. The therapeutic product is nuclear factor erythroid 2-like 2 (NRF2); (122) ocular pathologies , associated with retinitis pigmentosa, and the therapeutic product is pigment epithelium-derived factor (PEDF); (1 23) The eye condition is related to retinitis pigmentosa, and the therapeutic product is glutathione S-transferase. ferase PI1 (GSTP1), also known as PI; (124) ocular The condition is related to retinitis pigmentosa, and the therapeutic product is rod-derived cone survival factor (RDCVF). (125) The eye condition is related to retinitis pigmentosa, and the therapeutic product is rhodopsin ( (126) The eye condition is related to retinitis pigmentosa, and the therapeutic product is aldehyde-binding protein 1 (RLBP1); (127) ocular pathology Related to Gardt's disease, the therapeutic product is an anti-complement C5 aptamer; (128) ocular pathology , related to uveitis, the therapeutic product is double homeobox 4 (DUX4); ( 129) The eye condition is related to uveitis, and the therapeutic product is an NLR family pyridindone. 130) eye pathology is associated with uveitis and therapeutic The product is spleen-associated tyrosine kinase (SYK); (131) Ocular pathology involves the uveal In relation to inflammation, the therapeutic product is adrenocorticotropic hormone (ACTH); (132) ophthalmic The pathology is associated with uveitis, and the therapeutic product is caspase 1 (CASP1); (1 3 3) the ocular condition is associated with uveitis and the therapeutic product is an anti-CD59 therapeutic product (e.g., an anti-CD59 therapeutic product). CD59 therapeutic proteins (e.g., anti-CD59 monoclonal antibodies), or anti-CD5 9. Therapeutic RNA (e.g., anti-CD59 shRNA, anti-CD59 siRNA, or anti-CD59 CD59 miRNA), preferably an anti-CD59 monoclonal antibody); (134 The ocular condition is associated with uveitis, and the therapeutic product is an anti-complement monoclonal antibody or anti- Complement aptamers, anti-complement monoclonal antibodies or aptamers include anti-complement C1 monoclonal antibodies. Clonal antibody or aptamer, anti-complement C1q monoclonal antibody or aptamer -, anti-complement C1s monoclonal antibody or aptamer, anti-complement C2 monoclonal antibody Anti-complement C2a monoclonal antibody or aptamer, anti-complement C 2b monoclonal antibody or aptamer, anti-complement C3 monoclonal antibody or aptamer Aptamer, anti-complement C3a monoclonal antibody or aptamer, anti-complement C3b monoclonal antibody monoclonal antibody or aptamer, anti-complement C4 monoclonal antibody or aptamer, anti Complement C4a monoclonal antibody or aptamer, anti-complement C4b monoclonal antibody or aptamer, anti-complement C5 monoclonal antibody or aptamer, anti-complement C5a monoclonal antibody monoclonal antibody or aptamer, anti-complement C5b monoclonal antibody or aptamer mer, anti-complement C6 monoclonal antibody or aptamer, anti-complement C7 monoclonal antibody anti-complement C8 monoclonal antibody or aptamer, or anti-complement C8 monoclonal antibody or aptamer Preferably, the antibody is an anti-complement C9 monoclonal antibody or aptamer, or preferably an anti-complement C5 antibody. (135) Ocular pathologies are associated with corneal neovascularization, and therapeutic products inhibit insulin receptor groups. 136) Ocular pathology associated with corneal neovascularization, therapeutic products , NOTCH-regulated ankyrin repeat protein (NRARP); (137) ocular The condition is associated with diabetic retinopathy, and the therapeutic product is a NOTCH-regulated ankyrin repeat protein. 138) Ocular pathology is associated with diabetic retinopathy and is a therapeutic target for The product is alpha-2-antiplasmin (A2AP); (139) ocular pathologies , associated with diabetic retinopathy, and the therapeutic product is plasminogen (PLG); (14 0) The eye condition is related to diabetic retinopathy and the therapeutic product can be growth hormone. (141) The eye condition is related to diabetic retinopathy, and the therapeutic product is an insulin-like compound. Growth factor 1 (IGF1) can be used in combination with growth hormone. (142) The eye condition is related to diabetic retinopathy, and the therapeutic product acts as an interleukin (IL) inhibitor. 143 Eye pathology is associated with diabetic retinopathy and is a treatment-resistant The product is angiotensin I-converting enzyme 2 (ACE2), which combines with IL1B. (144) Eye conditions are associated with and can be treated with diabetic retinopathy. The therapeutic product is IRS1; (145) the ocular condition is related to diabetic retinopathy, and the therapeutic The product is an anti-integrin oligopeptide; (146) ocular pathology is diabetic retinopathy In the context of the present invention, the therapeutic product is an anti-placental growth factor (PGF) monoclonal antibody; (14 7) Eye conditions associated with Graves' ophthalmopathy (also known as Graves' orbitopathy) and treatment The product is an anti-CD40 monoclonal antibody; (148) the eye condition is Graves' ophthalmopathy. 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-inflammatory drug. Insulin-like growth factor 2 receptor (IGF2R) monoclonal antibody; (150) Ophthalmic The condition is associated with DME and the therapeutic product is an anti-integrin oligopeptide; (15 1) The ocular condition is related to DME and the therapeutic product is an anti-placental growth factor (PGF) monoclonal antibody. (152) The ocular condition is associated with DME, and the therapeutic product is RTP801. (153) Ocular pathology is associated with multiple sclerosis (MS)-related visual loss. (154) The eye condition is related to myopia, and the therapeutic product is ND1; (154) The eye condition is related to myopia, and the therapeutic product is is a matrix metalloproteinase 2 (MMP2) RNAi; (155) ocular The condition is associated with X-linked recessive ocular albinism, and the therapeutic product inhibits the G protein-coupled receptor 143( GPR143); (156) The ocular condition is associated with oculocutaneous albinism type 1, and therapeutic products is tyrosinase (TYR); (157) eye pathology is associated with optic neuritis, and therapeutic The product is caspase 2 (CASP2); (158) ocular pathology is associated with optic neuritis. The therapeutic product is an anti-leucine-rich repeat and Ig domain-containing protein 1 (LIN GO1) Monoclonal antibody; or (159) The ocular condition is polypoid choroidal retinal edema. In relation to vasculopathy, the therapeutic product is an anti-complement monoclonal antibody or an anti-complement aptamer. The anti-complement monoclonal antibody or aptamer may be an anti-complement C1 monoclonal antibody or Aptamer, anti-complement C1q monoclonal antibody / aptamer, anti-complement C1s monoclonal antibody Anti-complement C2 monoclonal antibody / aptamer, anti-complement C2a monoclonal antibody / aptamer monoclonal antibody or aptamer, anti-complement C2b monoclonal antibody or aptamer mer, anti-complement C3 monoclonal antibody or aptamer, anti-complement C3a monoclonal Antibody or aptamer, anti-complement C3b monoclonal antibody or aptamer, anti-complement C4 monoclonal antibody or aptamer, anti-complement C4a monoclonal antibody or Aptamer, anti-complement C4b monoclonal antibody or aptamer, anti-complement C5 monoclonal antibody anti-complement C5a monoclonal antibody or aptamer; Anti-complement C5b monoclonal antibody or aptamer, anti-complement C6 monoclonal antibody or aptamer, anti-complement C7 monoclonal antibody or aptamer, anti-complement C8 monoclonal antibody clonal antibody or aptamer, or anti-complement C9 monoclonal antibody or aptamer tamers, or preferably anti-complement C5 antibodies.

[0027] In certain embodiments of the methods described herein, the ocular condition is X-linked retinitis pigmentosa. (XLRP), and the therapeutic product is retinitis pigmentosa GTPase regulator (R In certain embodiments of any of the foregoing methods, the ocular condition is color vision deficiency. The therapeutic product is a cyclic nucleotide-gated channel beta 3 (C In certain embodiments of any of the foregoing methods, the ocular condition is color vision impairment. associated with disorders (e.g., CNGA3-linked color blindness), and the therapeutic product is a cyclic nucleotide and CNGA3. Certain implementations of any of the foregoing methods In morphology, the ocular pathology is associated with biallelic RPE65 mutation-associated retinal dystrophy. The therapeutic product is retinoid isomerohydrolase RPE65 (RPE65).

[0028] In certain embodiments of the methods described herein, the ocular condition is: (1) Batten-CL Related to N1, the therapeutic product is palmitoyl-protein thioesterase 1 (PPT1 (2) Batten-CLN2-related, the therapeutic product is a tripeptidyl-peptide (3) Batten-related CLN3, and the therapeutic product is Batten-related CLN3. (4) associated with uveitis, and therapeutic products include anti-interleukin (ATI) (5) uveitis-related, therapeutic product is an interleukin-6 (IL6) monoclonal antibody; , an anti-TNF alpha (TNF) monoclonal antibody; (6) diabetic macular edema (D ME), the therapeutic product is an anti-IL6 monoclonal antibody; (7) Red-green color blindness A related therapeutic product is L opsin (OPN1LW); (8) related to red-green color blindness; The therapeutic product is M opsin (OPN1MW); (9) associated with blue-cone monochromatism; The therapeutic products are M opsin (OPN1MW); (10) Leber congenital amaurosis-1 ( LCA 1), and the therapeutic product is guanylate cyclase 2D, retinal (GUC (11) Leber congenital amaurosis-2 (LCA 2)-related therapeutic product is a retinoid isomerohydrolase RPE65 (RPE65); (12) Reba -Related to congenital amaurosis-7 (LCA 7), the therapeutic product is cone-rod homeoboc (13) Leber congenital amaurosis-11 (LCA 11) is related to and cured The therapeutic product is inosine monophosphate dehydrogenase 1 (IMPDH1); (14) Congenital amaurosis-12 (LCA 12) is associated with the therapeutic product, which is a retinal degeneration 3, GUC Y2D regulator (RD3); (15) Leber congenital amaurosis-13 (LCA 13) In relation to the therapeutic product, retinol dehydrogenase 12 (RDH12); (1 6) Leber congenital amaurosis-15 (LCA 15) is associated with the therapeutic product, which is a tabby-like tan. protein 1 (TULP1); (17) Leber congenital amaurosis-16 (LCA-16) Related therapeutic products include potassium voltage-gated channel subfamily J member 13 (K CNJ13); (18) Associated with Leber's hereditary optic neuropathy (LHON) and therapeutically produced The enzyme is mitochondrially encoded NADH dehydrogenase 1 (MT-ND1). (19) In relation to LHON, the therapeutic product is the mitochondrially encoded NADH dehydrogenase 4 (MT-ND4); (20) related to LHON, therapeutic products are , mitochondrially encoded NADH dehydrogenase 6 (MT-ND6); (21) Neuromyelitis optica (NMO) is a condition in which therapeutic products are either anti-complement monoclonal antibodies or or anti-complement aptamer, and the anti-complement monoclonal antibody or aptamer is an anti-complement C 1 Monoclonal antibody or aptamer, anti-complement C1q monoclonal antibody or aptamer Aptamer, anti-complement C1s monoclonal antibody or aptamer, anti-complement C2 monoclonal antibody monoclonal antibody or aptamer, anti-complement C2a monoclonal antibody or aptamer, anti Complement C2b monoclonal antibody or aptamer, anti-complement C3 monoclonal antibody, or or aptamer, anti-complement C3a monoclonal antibody or aptamer, anti-complement C3b monoclonal antibody monoclonal antibody or aptamer, anti-complement C4 monoclonal antibody or aptamer -, anti-complement C4a monoclonal antibody or aptamer, anti-complement C4b monoclonal Antibody or aptamer, anti-complement C5 monoclonal antibody or aptamer, anti-complement C 5a monoclonal antibody or aptamer, anti-complement C5b monoclonal antibody or Aptamer, anti-complement C6 monoclonal antibody or aptamer, anti-complement C7 monoclonal antibody anti-complement C8 monoclonal antibody or aptamer, or is 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) Associated with uveitis, the therapeutic product is an anti-complement C5 monoclonal antibody; (24) In relation to uveitis, the therapeutic product is angiotensin I-converting enzyme (ACE). (25) Uveitis-related therapeutic products include interleukin 10 (IL10) (26) Uveitis is associated with a therapeutic product, which is an anti-TNF monoclonal antibody. (27) X-linked retinoschisis (XLRS) is associated with a therapeutic product called retinoschisin ( (28) Bardet-Biedl syndrome 1, and the therapeutic product is Bardet-Biedl syndrome 2. Biedl syndrome 1 (BBS1); (29) related to Bardet-Biedl syndrome 3, curable The therapeutic product is ADP-ribosylation factor-like GTPase 6 (ARL6); (30) Bal Related to Bardet-Biedl syndrome 5, therapeutic products include Bardet-Biedl syndrome 5 (BBS5) (31) Bardet-Biedl syndrome 6, and the therapeutic product is McKusick- Kaufman syndrome (MKKS); (32) related to Bardet-Biedl syndrome 10; The therapeutic product is Bardet-Biedl syndrome 10 (BBS10); (33) Bardet-Biedl associated with Paddle syndrome11, and the therapeutic product is tripartite motif-containing 32 (TRIM32). (34) Bardet-Biedl syndrome13, and therapeutic products are MKS1 (Modification Zone Complex Subunit 1); (35) Bardet-Bid associated with Lewy syndrome18, and the therapeutic product is BBSome-interacting protein 1 (BBIP1 ) associated with Bardet-Biedl syndrome19, and therapeutic products are intraflagellar transporters2 7 (IFT27); (37) Cone dystrophy-related, therapeutic product is guanidinium. Glucocorticoid cyclase activator 1A (GUCA1A); (38) Retinitis pigmentosa 13 A related therapeutic product is pre-mRNA processing factor 8 (PRPF8); (3 9) Retinitis pigmentosa 37 is associated with the therapeutic product, which is a nuclear receptor subfamily 2 group E member 3 (NR2E3); or (40) associated with Best disease, and the therapeutic product is Bestrophin 1 (BEST1).

[0029] In certain embodiments of the methods described herein, the ocular condition is characterized by biallelic RPE6 5 mutation-associated retinal dystrophies, and therapeutic products include retinoid isomerohydrochlorides. The enzyme is RPE65 (RPE65).

[0030] In certain embodiments of the methods described herein, the ocular condition is: (1) Batten-CL Related to N2, the therapeutic product is tripeptidyl-peptidase 1 (TPP1); 2) Associated with Usher syndrome type 1, the therapeutic product is myosin VIIA (MYO7A) (3) Usher syndrome type 1, and the therapeutic product is cadherin-related 23 (CD H23); (4) Associated with Usher syndrome type 2, the therapeutic product is protocadherin (5) Usher syndrome type 2-related, therapeutic product is Usherin (USH2A); (6) Associated with Usher syndrome type 3 and treatment The product is Clarrin 1 (CLRN1); (7) associated with Stargardt disease and therapeutic The product is ATP-binding cassette subfamily A member 4 (ABCA4); (8) Associated with Stargardt disease, therapeutic products include ELOVL fatty acid elongase 4 (ELOVL) (9) associated with red-green color blindness, the therapeutic product is L opsin (OPN1LW); (10) Associated with red-green color blindness, the therapeutic product is M opsin (OPN1MW); (11) Associated with blue-cone monochromatism, the therapeutic product is M opsin (OPN1MW) (12) Leber congenital amaurosis-1 (LCA 1) is associated with the therapeutic product guanylic acid. Cyclase 2D, retinal (GUCY2D); (13) Leber congenital amaurosis-2 (LCA 2), and the therapeutic product inhibits the retinoid isomerohydrolase RPE65 ( (14) Leber congenital amaurosis-4 (LCA 4)-related and therapeutic The product is aryl hydrocarbon receptor-interacting protein-like 1 (AIPL1); (15 ) Leber congenital amaurosis-7 (LCA 7) is associated with the therapeutic product, which is a cone-rod homeostasis. (16) Leber congenital amaurosis-8 (LCA-8)-related The therapeutic product is Crumbs cell polarity complex component 1 (CRB1); (17) Related to Barr congenital amaurosis-9 (LCA 9), the therapeutic product is a nicotinamide nucleotide NNMNAT1 (Neuromuscular Necrosis Factor 1) The therapeutic product is related to Centrosomal Protein 290 (CEP2 90); (19) Leber congenital amaurosis-11 (LCA 11) is associated with therapeutic The enzyme is inosine monophosphate dehydrogenase 1 (IMPDH1); (20) Leber Congenital amaurosis-15 (LCA 15) is associated with the therapeutic product, which is a protein that binds to tabby-like protein 1 (T (21) LHON-related, therapeutic product encoded by mitochondria. NADH dehydrogenase 4 (MT-ND4) is a methyltransferase (MT-ND4) that is associated with LHON. , the therapeutic product is mitochondrially encoded NADH dehydrogenase 6 (MT-N D6); (23) Associated with choroideremia, therapeutic products are Love Escort Tampa (24) X-linked retinoschisis (XLRS)-related therapeutic product (25) Retinoschisin (RS1) is a protein associated with Bardet-Biedl syndrome 1 and is a therapeutic agent. The therapeutic product is Bardet-Biedl syndrome 1 (BBS1); (26) Bardet-Biedl Related to syndrome 6, the therapeutic product is McKusick-Kaufman syndrome (MKKS). (27) Bardet-Biedl syndrome 10, and the therapeutic product is (28) Cone dystrophy, and the therapeutic product is Guanylate cyclase activator 1A (GUCA1A); (29) related to optic nerve atrophy In this context, the therapeutic product inhibits the activity of OPA1, a mitochondrial dynamin-like GTPase (OPA1). (30) Retinitis pigmentosa 1, and the therapeutic product is RP1 axonemal microtubule-associated (R P1); (31) Retinitis pigmentosa 2 is associated with, and the therapeutic product is ARL3 GTPa RP2 activator of se (RP2); (32) associated with retinitis pigmentosa 7 and therapeutic The product is peripherin 2 (PRPH2); (33) associated with retinitis pigmentosa 11; The therapeutic product is pre-mRNA processing factor 31 (PRPF31); (34) Retinitis pigmentosa 13 is associated with a therapeutic product that inhibits pre-mRNA processing factor 8 (PR PF8); (35) Retinitis pigmentosa37, which is associated with the nuclear receptor subfamily Family 2 group E member 3 (NR2E3); (36) Retinitis pigmentosa 38 A related therapeutic product is the MER proto-oncogene tyrosine kinase (MERTK). (37) Retinitis pigmentosa 40 is associated with the therapeutic product phosphodiesterase 6B (38) associated with retinitis pigmentosa41, and the therapeutic product is prominis (39) Retinitis pigmentosa56 is associated with a therapeutic product that inhibits photoreceptor activity. Intercellular matrix proteoglycan 2 (IMPG2); (40) Retinitis pigmentosa 62, and the therapeutic product is male germ cell-associated kinase (MAK); (41) Associated with membrane pigmentary degeneration 80, the therapeutic product is intraflagellar transport 140 (IFT140); or (42) Best disease, wherein the therapeutic product is bestrophin 1 (BEST1). do.

[0031] In certain embodiments of the methods described herein, the ocular condition is X-linked retinitis pigmentosa. (XLRP), and the therapeutic product is retinitis pigmentosa GTPase regulator (R In certain embodiments of any of the foregoing methods, the ocular condition is color vision deficiency. Therapeutic products are always related to cyclic nucleotide-gated channel beta 3 (CNGB3) or associated with color vision deficiency (e.g., CNGA3-linked color blindness), and the therapeutic product The nucleotide-gated channel alpha 3 (CNGA3) is a cytoplasmic nucleotide-gated channel.

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

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

[0034] In certain embodiments of the methods described herein, the recombinant viral vector is a cone-specific a cone-specific promoter, further comprising a nucleotide sequence encoding a heterologous promoter; The nucleotide sequence encoding the therapeutic product is operable to encode a nucleotide sequence encoding the therapeutic product. (1) the ocular condition is associated with red-green color blindness, and the therapeutic product is linked to L opsin (OPN1 (2) the ocular condition is associated with red-green color blindness, and the therapeutic product is M-opsin (OP (3) the ocular condition is associated with blue-cone monochromatism and the therapeutic product is M-ochromatism; (4) Ocular pathology associated with cone dystrophy and treatment or (5) the product is guanylate cyclase activator 1A (GUCA1A); The ocular condition is associated with blue-cone monochromatism (BCM), and the therapeutic product is L-opsin (OPN 1LW).

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

[0036] In certain embodiments of the methods described herein, a therapeutically effective amount of a therapeutic product is administered to said human It is produced by human retinal cells in the target subject.

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

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

[0039] In certain embodiments of the methods described herein, the retinal ganglion cells are midget cells, Parasol cells, bistratified cells, giant retinal ganglion cells, photosensitive ganglion cells, and / or murine retinal ganglion cells It's Laglia.

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

[0041] In certain embodiments of the methods described herein, the recombinant viral vector is It is a V8 vector.

[0042] In certain embodiments of the methods described herein, the method further comprises, after the administering step, applying infrared radiation. Further comprising monitoring the temperature of the surface of the eye using a thermal camera. In a specific embodiment, the infrared thermal camera is a FLIR T530 infrared thermal camera. In a particular embodiment, the infrared thermal camera is a FLIR T420 infrared thermal camera. The infrared thermal camera is a FLIR T440 infrared thermal camera. The infrared thermal camera is a Fluke Ti400 infrared thermal camera. The infrared thermal camera is a FLIRE60 infrared thermal camera. The infrared resolution of the thermal camera is 75,000 pixels or greater. The thermal sensitivity of the infrared thermal camera is 0.05°C or less at 30°C. The field of view (FOV) of the linear thermal camera is 25° x 25° or less.

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

[0044] In certain embodiments, the recombinant vector used to deliver the therapeutic product comprises: It should have tropism for ocular cells, e.g., human retinal cells (e.g., photoreceptor cells). Such vectors include non-replicating recombinant adeno-associated viral vectors ("rAAV"). It is particularly preferred that the recombinant vector contains an AAV8 capsid. Lentiviral vectors, vaccinia virus vectors, or "naked DNA" Other recombinant vectors, including but not limited to non-viral expression vectors, are referred to as constructs. Viral vectors may be used. Preferably, expression of the therapeutic product is controlled by appropriate expression regulators. Elements, for example, (1) CAG promoter; (2) CBA promoter; (3) C MV promoter; (4) PR1.7 promoter; (5) rhodopsin kinase (GRK 1) photoreceptor-specific enhancer-promoter (6) hCARp promoter; (7 ) hRKp; (8) cone photoreceptor-specific human arrestin 3 (ARR3) promoter; ( 9) Rhodopsin promoter; or (10) U6 promoter. and other expression control elements that enhance expression of the therapeutic product driven by the vector. introns (e.g., chicken β-actin introns, mouse minute virus human factor IX intron (e.g., FIX truncated intron 1); ), β-globin splice donor / immunoglobulin heavy chain splice acceptor Ron, Adenovirus Splice Donor / Immunoglobulin Splice Acceptor Int Ron, SV40 late splice donor / splice acceptor (19S / 16S) in Tron, and hybrid adenovirus splice donor / IgG splice acceptor Introns and poly(A) signals, e.g., rabbit β-globin poly(A) signal, human Human growth hormone (hGH) poly(A) signal, SV40 late poly(A) signal, synthetic poly(A) The polyA signal can include the bovine growth hormone (bGH) polyA signal. For example, Powell and Rivera-Soto, 2015, Discov See .Med.,19(102):49-57.

[0045] In certain embodiments of the methods described herein, the therapeutically effective dose of the recombinant vector comprises: (1) Injection into the subretinal space (e.g., via the suprachoroidal space or via a periphery injection) without vitrectomy (2) administered into the suprachoroidal space; (3) administered into the space outside the sclera. (i.e., juxtascleral administration), (4) administered into the subretinal space via vitrectomy, or (5) It is administered into the vitreous cavity, and the volume is 50 to 100 μl or 100 μl depending on the administration method. ~500 μl, preferably in the range of 100 to 300 μl, most preferably 250 μl. In certain embodiments, a therapeutically effective dose of the recombinant vector is administered in a volume of 100 μl or less. In certain embodiments, the solution is administered suprachoroidally in a volume of, for example, 50 to 100 μl. A therapeutically effective dose of the recombinant vector is delivered to the outer surface of the sclera (e.g., a posterior juxtascleral depot procedure). (depending on the volume) 500 μl or less, for example, 10-20 μl, 20-50 μl, 50- 100μl, 100-200μl, 200-300μl, 300-400μl, or 4 In certain embodiments, a therapeutically effective dose of recombinant human leukocyte antigen (VEGA) is administered in a volume of 00 to 500 μl. The vector is delivered into the subretinal space via pericardial injection in 50-100 μl or 100-500 μl Preferably, the volume is in the range of 100-300 μl, most preferably 250 μl. do.

[0046] In certain embodiments, optokinetic nystagmus (OKN) is assessed to measure the patient's visual acuity. In certain embodiments, OKN is prepared using the method described, for example, in Cetinkaya et al., 2 008,Eye,22:77-81;Hyon et al.,2010,IOVS,5 1(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.,Obje ctive Assessment of Visual Performance U sing Optokinetic Nystagmus in Young Chil dren,October 2016, <anzctr.org.au / AnzctrA attachments / 371914-OKN%20protocol.pdf>; and Objective Acuity and Aier Eye Hospital G roup Announce Strategic Cooperation Agre ement,Cision PR Newswire,July 25,2019,In Obtained from the Internet <prnewswire.com / news-releases / o bjective-acuity-and-aier-eye-hospital-gr oup-announce-a-strategic-cooperation-agr eement-300891165.html (each of which is incorporated herein by reference in its entirety). The present invention is performed using the methods and / or devices described and disclosed in the It is possible to do so.

[0047] Without being bound by theory, this visual acuity screening uses the principle of the OKN involuntary reflex. Using the OKN, objectively assess whether the patient's eyes can track a moving target. Therefore, no verbal communication is required between the examiner and the patient. , using OKN to measure visual acuity in pre-verbal and / or non-verbal patients. In certain embodiments, OKN can be used to treat 1-month-old, 2-month-old, 3-month-old, and , 4 months old, 5 months old, 6 months old, 7 months old, 8 months old, 9 months old, 10 months old, 11 months old Age in months, 1 year old, 1.5 years old, 2 years old, 2.5 years old, 3 years old, 3.5 years old, 4 years old, 4.5 years old In one particular embodiment, an iPad is used to measure the visual acuity of a patient who is 18 years old or 5 years old. used to measure visual acuity through detection of the OKN reflex while patients watch movements on an iPad do.

[0048] Without being bound by theory, this visual acuity screening uses the principle of the OKN involuntary reflex. Using the OKN, objectively assess whether the patient's eyes can track a moving target. Therefore, no verbal communication is required between the examiner and the patient. , using OKN to measure visual acuity in pre-verbal and / or non-verbal patients. In one particular embodiment, OKN can be used to treat 1.5-month-old, 2-month-old, 3-month-old, and month age, 4 months age, 5 months age, 6 months age, 7 months age, 8 months age, 9 months age, 10 months age, 1 month old, 1 year old, 1.5 years old, 2 years old, 2.5 years old, 3 years old, 3.5 years old, 4 years old, 4 In another specific embodiment, the visual acuity of a patient is measured at or under the age of 5. Using KN, 1-2 month olds, 2-3 month olds, 3-4 month olds, 4-5 month olds, 5-6 month olds Age: 6-7 months, 7-8 months, 8-9 months, 9-10 months, 10-11 months , 11 months to 1 year old, 1 to 1.5 years old, 1.5 to 2 years old, 2 to 2.5 years old, 2.5 to 3 years old, 3-3.5 years old, 3.5-4 years old, 4-4.5 years old, or 4.5-5 years old In another specific embodiment, OKN is used to measure the visual acuity of patients between the ages of 6 months and 5 months. In one particular embodiment, an iPad is used to measure the visual acuity of a patient aged 18+. We measure visual acuity through the detection of the OKN reflex while a subject watches movements on an iPad.

[0049] In certain embodiments, visual acuity is improved in patients exhibiting Batten-CLN2-associated visual loss. In this case, the patient is administered an AAV encoding tripeptidyl-peptidase 1 (TPP1), preferably or by measuring OKN before treatment with AAV8 or AAV9. Specifically, patients presenting with Batten-CLN2-related visual loss are at the ages listed above. and / or within the age ranges set forth above. In certain embodiments, the visual acuity is measured by a - Patients up to 5 years of age with CLN2-related visual loss will be screened for tripeptide Using an AAV encoding dipeptidase 1, preferably AAV8 or AAV9 In certain embodiments, OKN is assessed by measuring OKN after treatment. N-based visual acuity assessment determined that visual acuity was not reduced after treatment with AAV gene therapy In certain embodiments, OKN-based visual acuity assessment is performed using AAV gene therapy. Post-treatment patients had visual acuity of 5%, 10%, 15%, 20%, 25%, 30%, and 35% , 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85% , 90%, 95%, or 100% improvement. OKN-based visual acuity assessment may improve visual acuity in patients after treatment with AAV gene therapy. Determined not to worsen.

[0050] In certain embodiments, visual acuity is improved in patients exhibiting Batten-CLN2-associated visual loss. The patient is then transfected with an AAV encoding TPP1, preferably AAV8 or AAV9. This is assessed by measuring OKN before treatment. Patients presenting with N2-related visual loss are of the ages and / or within the age ranges listed above. In certain embodiments, the visual acuity is measured at a maximum of 1000 subjects exhibiting Batten-CLN2-associated visual loss. In patients up to 5 years of age, patients were assigned to a gene encoding tripeptidyl-peptidase 1 (A1). We measured OKN after treatment with AV, preferably AAV8 or AAV9. In certain embodiments, visual acuity assessment based on OKN is performed using AAV gene In certain embodiments, the OK therapy is administered to a subject in need thereof. N-based visual acuity assessment showed that visual acuity was improved in patients treated with AAV gene therapy, at least Both are 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50% , 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or In a particular embodiment, the OKN-based Visual acuity assessment will confirm that visual acuity does not further deteriorate in patients after treatment with AAV gene therapy. It is decided that:

[0051] In certain embodiments, visual acuity is improved in patients presenting with Batten-CLN1-associated visual loss. Patients were identified as having a gene encoding palmitoyl-protein thioesterase 1 (PPT1). Measuring OKN before treatment with AAV, preferably AAV8 or AAV9 Specifically, patients up to 5 years of age with Batten-CLN1-related visual loss are evaluated by Patients up to age 15 are of the ages and / or within the age ranges set forth above. In embodiments, visual acuity is assessed in a patient presenting with Batten-CLN1-associated visual loss. , after treatment with an AAV encoding PPT1, preferably AAV8 or AAV9 In certain embodiments, the OKN-based Visual acuity assessment will determine that visual acuity is not reduced following treatment with AAV gene therapy. In certain embodiments, OKN-based visual acuity assessment is performed on patients following treatment with AAV gene therapy. In patients with visual acuity loss, the following were reported: 5%, 10%, 15%, 20%, 25%, 30%, 35%, and 40% 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, In certain embodiments, the OKN-based Visual acuity assessment based on AAV gene therapy is expected to prevent further deterioration of visual acuity in patients after treatment. Decide to do so.

[0052] In certain embodiments, visual acuity is improved in patients presenting with Batten-CLN1-associated visual loss. The patient is then transfected with an AAV encoding PPT1, preferably AAV8 or AAV9. This is assessed by measuring OKN before treatment. Patients presenting with N1-related visual loss are of the ages and / or within the age ranges listed above. In certain embodiments, the visual acuity is measured at a maximum of 100 mg / kg of a subject exhibiting Batten-CLN1-associated visual loss. In patients up to 5 years of age, the patient is administered an AAV encoding PPT1, preferably an AAV The effect of AAV9 on the immune system is assessed by measuring OKN after treatment with AAV9 or AAV1. In certain embodiments, OKN-based visual acuity assessment is performed to assess visual acuity following treatment with AAV gene therapy. In certain embodiments, the OKN-based visual acuity assessment determines whether the force is reduced. Visual acuity improved by at least 5%, 10%, or 15% in patients treated with AAV gene therapy. %, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65 %, 70%, 75%, 80%, 85%, 90%, 95%, or at least 100% improvement In certain embodiments, OKN-based visual acuity assessment is performed based on the AAV gene. To determine whether there is further deterioration of vision in patients following treatment with fluoroscopy.

[0053] In certain embodiments, visual acuity is improved in patients exhibiting Batten-CLN3-associated visual loss. In this case, the patient is administered an AAV encoding battenin (CLN3), preferably AAV8 or This is assessed by measuring OKN before treatment with AAV9. Patients presenting with Batten-CLN3-associated visual loss are of the ages listed above and / or have the following characteristics: In certain embodiments, the visual acuity is determined to be in the range of 0.01 to 0.01%. Patients up to 5 years of age presenting with ataxia were randomly assigned to a gene encoding battenin (CLN3). Measure OKN after treatment with an AAV, preferably AAV8 or AAV9 In certain embodiments, visual acuity assessment based on OKN is performed by AAV It is determined that vision does not decrease after treatment with gene therapy. In certain embodiments, , OKN-based visual acuity assessment showed that visual acuity improved in patients after treatment with AAV gene therapy. 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 5 5%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 10 In certain embodiments, the visual acuity assessment based on OKN is determined to be 0% improved. Determine that there is no further deterioration of vision in patients following treatment with AV gene therapy.

[0054] In certain embodiments, visual acuity is improved in patients exhibiting Batten-CLN3-associated visual loss. In this case, the patient is administered an AAV encoding battenin (CLN3), preferably AAV8 or This is assessed by measuring OKN before treatment with AAV9. Patients presenting with Batten-CLN3-associated visual loss are of the ages listed above and / or have the following characteristics: In certain embodiments, the visual acuity is determined to be in the range of 0.01 to 0.01%. Patients up to 5 years of age presenting with ataxia were randomly assigned to a gene encoding battenin (CLN3). Measure OKN after treatment with an AAV, preferably AAV8 or AAV9 In certain embodiments, visual acuity assessment based on OKN is performed by AAV It is determined that vision does not decrease after treatment with gene therapy. In certain embodiments, , OKN-based visual acuity assessment showed that visual acuity improved in patients after treatment with AAV gene therapy. 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% improvement. In certain embodiments, the OKN Visual acuity assessment based on AAV gene therapy showed that visual acuity worsened in patients after treatment with AAV gene therapy. Decide not to.

[0055] In certain embodiments, visual acuity is improved in patients exhibiting Batten-CLN6-associated visual loss. In this case, the patient is administered an AAV encoding the CLN6 transmembrane ER protein (CLN6), preferably This was assessed by measuring OKN before treatment with AAV8 or AAV9. Specifically, patients up to 5 years of age who present with Batten-CLN6-related visual loss , are of the ages and / or are within the age ranges set forth above. Visual acuity was assessed in patients with Batten-CLN6-associated visual loss by identifying patients with CLN6 transmembrane AAV encoding the ER protein (CLN6), preferably AAV8 or AAV9 In certain embodiments, the OKN is assessed by measuring the OKN after treatment with Therefore, OKN-based visual acuity assessment demonstrated that visual acuity was not reduced after treatment with AAV gene therapy. In certain embodiments, OKN-based visual acuity assessment is performed to determine whether or not the patient is a candidate for AAV gene therapy. Visual acuity improved by 5%, 10%, 15%, 20%, 25%, and 30% in patients after treatment with , 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80% , 85%, 90%, 95%, or 100% improvement. In this study, OKN-based visual acuity assessment was performed in patients treated with AAV gene therapy. The power decides not to make things worse.

[0056] In certain embodiments, visual acuity is improved in patients exhibiting Batten-CLN6-associated visual loss. In this case, the patient is administered an AAV encoding the CLN6 transmembrane ER protein (CLN6), preferably This was assessed by measuring OKN before treatment with AAV8 or AAV9. Specifically, patients up to 5 years of age who present with Batten-CLN6-related visual loss , are of the ages and / or are within the age ranges set forth above. Visual acuity was assessed in patients with Batten-CLN6-associated visual loss by identifying patients with CLN6 transmembrane AAV encoding the ER protein (CLN6), preferably AAV8 or AAV9 In certain embodiments, the OKN is assessed by measuring the OKN after treatment with Therefore, OKN-based visual acuity assessment demonstrated that visual acuity was not reduced after treatment with AAV gene therapy. In certain embodiments, OKN-based visual acuity assessment is performed to determine whether or not the patient is a candidate for AAV gene therapy. Visual acuity improved by at least 5%, 10%, 15%, 20%, 25% in patients after treatment with %, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75 %, 80%, 85%, 90%, 95%, or at least 100% improvement. In certain embodiments, OKN-based visual acuity assessment is performed following treatment with AAV gene therapy. Determine whether there is further deterioration of vision in patients after placement.

[0057] In certain embodiments, visual acuity is improved in patients presenting with Batten-CLN7-associated visual loss. Patients were randomly assigned to major facilitator superfamily domain-containing 8 (MFSD8) ), preferably AAV8 or AAV9, before treatment with OKN Specifically, patients with Batten-CLN7-related visual loss are assessed by measuring Patients up to 5 years of age who are of the ages and / or within the age ranges listed above In certain embodiments, visual acuity is improved in patients exhibiting Batten-CLN7-associated visual loss. In the method, the patient is treated with an AAV encoding MFSD8, preferably AAV8 or AAV9. In certain embodiments, the OKN is assessed by measuring the OKN after treatment with , and visual acuity assessment based on OKN showed no loss of visual acuity after treatment with AAV gene therapy. In certain embodiments, OKN-based visual acuity assessment is performed after AAV gene therapy. The visual acuity of patients after treatment using 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, The determination is made to improve by 85%, 90%, 95%, or 100%. In this study, OKN-based visual acuity assessment was performed to assess visual acuity in patients treated with AAV gene therapy. Determined not to make things worse.

[0058] In certain embodiments, visual acuity is improved in patients presenting with Batten-CLN7-associated visual loss. The patient is then transfected with an AAV encoding MFSD8, preferably AAV8 or AAV9. This is assessed by measuring OKN before treatment. Patients presenting with LN7-related visual loss are of the age and / or within the age ranges listed above. In certain embodiments, the visual acuity is measured in a patient with Batten-CLN7-associated visual loss. In patients up to 5 years of age, the patient is administered an AAV encoding MFSD8, preferably A It is assessed by measuring OKN after treatment with AV8 or AAV9. In certain embodiments, OKN-based visual acuity assessment is performed after treatment with AAV gene therapy. In certain embodiments, the OKN-based visual acuity assessment determines that the visual acuity is not reduced. reported that vision improved by at least 5%, 10%, or 20% in patients after treatment with AAV gene therapy. 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or at least 100% In certain embodiments, the visual acuity assessment based on the OKN is determined to improve the AAV It is determined that there is no further deterioration of vision in patients following treatment with gene therapy.

[0059] Subretinal administration via vitrectomy is a surgical procedure performed by a trained retinal surgeon. The procedure involves vitrectomy in subjects under local anesthesia and subretinal injection of gene therapy into the retina. (e.g., Campochiaro et al., 2017, Hum Gen Th See J. Chem. Soc. 28(1):99-111, which is incorporated herein by reference in its entirety. Alternatively, subretinal administration can be performed without vitrectomy. In embodiments, subretinal administration without vitrectomy can be inserted into the suprachoroidal space, and the suprachoroidal A catheter that can be passed through the cavity toward the posterior pole and injects a fine needle into the subretinal space at the posterior pole. Subretinal drug delivery devices, such as those using suprachoroidal catheters to inject drugs into the subretinal space via the suprachoroidal space (e.g., Baldassarre et al., 201 7, Subretinal Delivery of Cells via the S uprachoroidal Space:Janssen Trial.In:Sch wartz et al.(eds)Cellular Therapies for Retinal Disease, Springer, Cham; International Patent Application Publication No. See WO2016 / 040635A1; each of which is incorporated herein by reference in its entirety. In another particular embodiment, subretinal administration without vitrectomy is In other words, the recombinant vector is delivered to the vitreous body via perivitreous injection without vitrectomy. Peri-retinal injections (i.e., around the optic disc, fovea, and macula in the posterior segment of the eye) This can be achieved by intravitreal injection. Suprachoroidal administration procedures involve administering a drug to the suprachoroidal space of the eye, usually via microinjection. This is performed using a suprachoroidal drug delivery device such as a needle-equipped microinjector. (e.g., Hariprasad, 2016, Retinal Physicia n 13:20-23;Goldstein,2014,Retina Today 9 (5):82-87; each of which is incorporated herein by reference in its entirety. (It is included).

[0060] The method for depositing recombinant vectors in the suprachoroidal space according to the invention described herein is A suprachoroidal drug delivery device that can suprachoroidal drug delivery devices manufactured by Hari Edical, Inc. Prasad, 2016, Retinal Physician 13:20-23 (See reference) and MedOne suprachoroidal catheter. In order to deposit a recombinant vector into the subretinal space via the suprachoroidal space according to the present invention, A subretinal drug delivery device that can be used for this purpose is available from Janssen Pharmac Subretinal drug delivery devices manufactured by Neurologicals, Inc. (e.g., International Patent See Patent Application Publication No. WO2016 / 040635 A1), including, but not limited to: The transfection into the subretinal space via the peri-injection approach according to the invention described herein is not limited to the above. A subretinal drug delivery device that can be used to deposit the vector is or inserted into the sclera via the inferior side of the eye (e.g., at the 2 or 10 o'clock position) and completely into the vitreous. A sharp needle that can be passed through the sclera and injected into the opposite retina, as well as inserted into the sclera. The subretinal cannula can be inserted into the eye and threaded through the vitreous to the area of ​​the desired injection. In certain embodiments, the outer sclera may be inserted into the sclera. For surface administration, the tip of the cannula is inserted into the scleral surface and placed directly in apposition to the scleral surface. This is accomplished by a juxtascleral drug delivery device that includes a cannula that allows

[0061] Suprachoroidal, subretinal, juxtascleral, intravitreal, subconjunctival, and / or intraretinal administration may be performed using soluble It should result in delivery of the therapeutic product to the retina, vitreous humor, and / or aqueous humor. Membrane cells, e.g., rods, cones, retinal pigment epithelium, horizontal, bipolar, amacrine, ganglion, and / or or expression of a therapeutic product by Muller cells in the retina, vitreous humor, and / or aqueous humor. In certain embodiments, the therapeutic product is delivered and maintained continuously. Therapeutic product concentrations may be maintained at low levels due to the increased production of the therapeutic product. It can be measured in patient samples of vitreous and / or aqueous humor from the anterior chamber of the eye. Alternatively, the vitreous humor concentration can be estimated and measured by measuring the patient's serum concentration of the therapeutic product. and / or can be monitored - the ratio of systemic exposure to the therapeutic product to the vitreous exposure is about 1:90,000. (For example, Xu L, et al., 2013, Invest .Opthal.Vis.Sci.54:1616-1624, p.1621 and p.1 Ranibizumab reported in Table 5 of 623 (incorporated herein by reference in its entirety). (See vitreous and serum concentrations of riboflavin.)

[0062] Pharmaceutical compositions suitable for suprachoroidal, subretinal, juxtascleral, intravitreal, subconjunctival, and / or intraretinal administration The pharmaceutical composition comprises a physiologically compatible aqueous buffer, a surfactant, and optional excipients. , a suspension of the recombinant vector in a formulation buffer.

[0063] The present invention provides a high dose bottle of a therapeutic product that dissipates over time to produce peak and trough levels. This product has several advantages over standard of care treatments, which involve repeated ocular injections of steroids. Sustained expression of a therapeutic product, as opposed to repeated injections, allows for more consistent levels of Allows antibodies to be present at the site of action, resulting in fewer injections being required It also means fewer doctor visits, which is less risky and more convenient for patients. Consistent protein production is better because it reduces the chance of edema rebound. Furthermore, in certain embodiments, the polypeptides expressed from recombinant vectors may be useful in clinical trials. Therapeutic products used in this study may differ from those directly injected due to the different microenvironments they exist in during and after translation. Without being bound by any particular theory, This allows the therapeutic product delivered to the site of action to be " Diffusion, bioactivity, distribution, affinity, pharmacokinetics, and immunogenicity to make it "bio-better" The resulting therapeutic products have different characteristics.

[0064] In addition, when the therapeutic product is an antibody, it is expressed from a recombinant vector in vivo. The antibodies produced by recombinant technology are susceptible to protein aggregation and protein oxidation. Aggregation is likely to be caused by high protein concentrations, manufacturing equipment, and Surface interactions with the container and the protein due to purification using certain buffer systems. These conditions that promote aggregation are problems associated with protein production and storage. It is not present in antibody expression in the present study. Oxidation is also associated with protein production and storage and is caused by stressful cell culture conditions, metals, and air. contact with the environment and impurities in buffers and excipients. Proteins expressed from recombinant vectors in vitro can also be oxidized under stressful conditions. However, humans, and many other organisms, not only mitigate oxidative stress but also sometimes The body has an antioxidant defense system that repairs and / or reverses oxidation. Proteins produced in vivo are unlikely to be in an oxidized form. Both can affect efficacy, pharmacokinetics (clearance), and immunogenicity.

[0065] Unlike small molecule drugs, biologics typically have different efficacy, pharmacokinetic, and safety profiles. It contains a mixture of many variants with different modifications or forms that have the same file. For therapeutic products that are post-translationally modified during expression in the It is essential that all molecules produced by either approach are fully post-translationally modified. Rather, the population of such therapeutic products produced is sufficient to demonstrate efficacy. Post-translational modifications (e.g., from about 1% to about 10% of the population, from about 1% to about 20% of the population, from about It should comprise 1% to about 50%, or about 10% to about 50% of the population. The goal of the gene therapy treatment provided to the patient is to slow or stop the progression of the ocular condition, and The goal is to slow or prevent vision loss with minimal intervention / invasive procedures. CVA (best corrected visual acuity), intraocular pressure, slit lamp biomicroscopy, indirect ophthalmoscopy, SD-OCT (SD-optical coherence tomography), electroretinography (ERG) The risk of vision loss, infection, inflammation, and other safety events, such as retinal detachment, may be monitored. Symptoms may also be monitored. In certain embodiments, retinal thickness is monitored to determine the severity of the disease as described herein. Without being bound by any particular theory, certain In embodiments of the present invention, retinal thickness may be used as a clinical readout, and a decrease in retinal thickness may be The larger the retinal thickness or the longer the time to retinal thickening, the more effective the treatment. , can be determined, for example, by SD-OCT, which is a low-coherence interferometry to determine the echo time delay and amplitude of backscattered light reflected from the object of interest. OCT is a three-dimensional imaging technique used to visualize tissue samples with an axial resolution of 3 to 15 μm. SD-OCT is able to scan layers of the brain (e.g., the retina) more efficiently than previous techniques. also improves axial resolution and scan speed (Schuman, 2008, Trans. Am. Opthamol. Soc. 106:426-458). Retinal function can be assessed by, for example, E ERG can be determined by ERG, a retinal imaging technique approved by the FDA for use in humans. It is a non-invasive electrophysiological test of the function of the light-sensitive cells (rods and cones) of the eye, The ganglion cells to which it is connected, and in particular its response to light stimuli, are examined. 4.1 Exemplary Embodiments 4.1.1 Set 1 1. A method of subretinal administration without vitrectomy for treating ocular conditions, comprising administering the treatment a nucleotide sequence encoding a therapeutic product into the subretinal space of the eye of a human subject in need thereof. Administering a recombinant viral vector to express the therapeutic product and treat the ocular condition. the method comprising: providing a vitrectomy to the eye of the human patient; and the method does not comprise performing a vitrectomy on the eye of the human patient. 2. The administering step comprises administering to the subretinal space of the eye of the human subject and to the suprachoroidal space of the eye of the human subject. 2. The method of paragraph 1, comprising administering the recombinant viral vector therapeutic product via Law. 3. The administration step can be inserted into the suprachoroidal space and passed through the suprachoroidal space toward the posterior pole. and the use of a subretinal drug delivery device comprising a catheter with a fine needle for injection into the subretinal space at the posterior pole. 3. The method of claim 2, wherein the method is 4. The administering step includes inserting the catheter of the subretinal drug delivery device into the suprachoroidal space. 4. The method of paragraph 3, comprising: 5. A method of suprachoroidal administration for treating an ocular condition, comprising administering to a human subject in need thereof a recombinant viral vector containing a nucleotide sequence encoding a therapeutic product into the suprachoroidal space of the eye; administering a therapeutic agent to the eye to express said therapeutic product and effect treatment of said condition of the eye. Hmm, the above method. 6. The administration step delivers the recombinant viral vector to the suprachoroidal space for suprachoroidal drug delivery. 6. The method of paragraph 5, wherein the method is by injection using a device. 7. Paragraphs 5 or 6, wherein the suprachoroidal drug delivery device is a microinjector. The method described below. 8. A method of administration to the extrascleral space for treating an ocular condition, comprising administering to a subject in need of treatment A recombinant human subject's eye comprising a nucleotide sequence encoding a therapeutic product is attached to the outer surface of the sclera of the eye. and administering the viral vector to express the therapeutic product to treat the condition of the eye. The method further comprises: 9. The administration step involves inserting the tip of the cannula into the scleral surface and bringing it into direct apposition with the scleral surface. by use of a juxtascleral drug delivery device including a cannula capable of 8. The method according to claim 8. 10. The administration step includes inserting the tip of the cannula onto the scleral surface and applying the cannula onto the scleral surface. 10. The method of paragraph 9, comprising direct juxtaposition. 11. Paragraph 1, wherein the therapeutic product is not an anti-human vascular endothelial growth factor (hVEGF) antibody. The method according to any one of claims 1 to 10. 12. The eye condition is not related to neovascular age-related macular degeneration (nAMD), 12. The method according to any one of claims 11 to 11. 13. A method of subretinal administration with vitrectomy for treating an ocular condition, comprising administering to a subject requiring treatment and administering to the subretinal space of the eye of a human subject a composition comprising a nucleotide sequence encoding a therapeutic product. and administering a recombinant viral vector to express the therapeutic product and treat the condition of the eye. and performing a vitrectomy on the eye of said human patient, wherein said therapeutic product , wherein the antibody is not an anti-human vascular endothelial growth factor (hVEGF) antibody. 14. The method of paragraph 13, wherein the vitrectomy is a partial vitrectomy. 15. A method of subretinal administration for treating an ocular condition, comprising administering to a human subject in need thereof The therapeutic product is applied to the subretinal space around the optic disc, fovea, and macula, located in the posterior segment of the eye. and administering a recombinant viral vector containing a nucleotide sequence encoding the therapeutic product to produce the therapeutic product. and performing a vitrectomy on the eye of the human patient, causing the eye to develop a vitreous stimulating agent, resulting in treatment of the condition of the eye. The method does not include: 16. The method of paragraph 15, wherein the administering step is by intravitreal injection. 17. The transvitreal injection is performed by inserting a sharp needle into the sclera via the upper or lower eye side, The virus is then allowed to completely pass through the vitreous body, and the recombinant viral vector is injected into the subretinal space on the opposite side. 17. The method of paragraph 16, comprising: 18. The transvitreal injection is performed by inserting a trocar into the sclera, inserting a cannula into the trocar, and and injecting the recombinant viral vector into the contralateral subretinal space via the retina. 17. The method according to paragraph 16. 19. The method of any one of paragraphs 15 to 18, wherein the therapeutic product is an anti-hVEGF antibody. How to post. 20. The method of paragraph 19, wherein the anti-hVEGF antibody is an anti-hVEGF antigen-binding fragment. The method described. 21. The anti-hVEGF antigen-binding fragment is Fab, F(ab')2, or a single antibody. 21. The method of paragraph 20, wherein the antibody is a fragment chain variable (scFv). 22. The anti-hVEGF antibody has 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. 10. The method according to any one of claims 1 to 9. 23. The anti-hVEGF antibody comprises light chain CDRs 1 to 3 of SEQ ID NOs: 14 to 16 and CDRs 1 to 3 of SEQ ID NOs: 15 to 17. Paragraph 19, which contains heavy chain CDRs 1-3 of SEQ ID NOs. 17-19 or SEQ ID NOs. 20, 18, and 21. The method according to any one of claims 1 to 21. 24. The eye condition is nAMD, dry age-related macular degeneration (dry AMD), retinal vein associated with recurrent retinal occlusion (RVO), diabetic macular edema (DME), or diabetic retinopathy (DR) The method according to any one of paragraphs 19 to 23, 25. The method according to any one of paragraphs 19 to 23, wherein the eye condition is associated with nAMD. Law. 26. (1) The eye condition is associated with Batten-CLN1, and the therapeutic product is a palmitoyltransferase. toil-protein thioesterase 1 (PPT1); (2) the ocular condition is associated with Batten-CLN2 and the therapeutic product is a tripeptide le-peptidase 1 (TPP1); (3) The pathology of the eye is associated with Batten-CLN3, and the therapeutic product is a battenin ( CLN3); (4) the ocular condition is associated with Batten-CLN6, and the therapeutic product is a CLN6 transmembrane a common ER protein (CLN6); (5) The eye condition is associated with Batten-CLN7, and the therapeutic product is a major fasciculation. is tator superfamily domain containing 8 (MFSD8); (6) The eye condition is associated with Usher syndrome type 1, and the therapeutic product is myosin V IIA (MYO7A); (7) The eye condition is associated with Usher syndrome type 1, and the therapeutic product is a cadherin Related 23 (CDH23); (8) The eye condition is associated with Usher syndrome type 2, and the therapeutic product is a protococcid. Helin-related 15 (PCDH15); (9) The eye condition is associated with Usher syndrome type 2, and the therapeutic product is phosphorus (USH2A); (10) The eye condition is associated with Usher syndrome type 3 and the therapeutic product is clarinet. 1 (CLRN1); (11) The eye condition is associated with Stargardt's disease, and the therapeutic product is an ATP-binding protein. Set subfamily A member 4 (ABCA4); (12) The eye condition is associated with Stargardt's disease and the therapeutic product is ELOVL lipid. fatty acid elongase 4 (ELOVL4); (13) The ocular condition is associated with uveitis and the therapeutic product is an anti-interleukin (AIL)-1 inhibitor. 6 (IL6) monoclonal antibody; (14) The eye condition is associated with uveitis and the therapeutic product is an anti-TNF alpha ( TNF) monoclonal antibodies; (15) The eye condition is associated with diabetic macular edema (DME), and the therapeutic product is an anti- It is an IL6 monoclonal antibody; (16) The eye condition is associated with red-green color blindness, and the therapeutic product is a compound that inhibits L-opsin (OPN1 LW); (17) The eye condition is associated with red-green color blindness, and the therapeutic product is a compound that inhibits M opsin (OPN1 MW); (18) The eye condition is associated with blue-cone monochromatism, and the therapeutic product is a compound that inhibits M opsin ( OPN1MW); (19) The eye condition is associated with Leber congenital amaurosis-1 (LCA 1), and the therapeutic The product is guanylate cyclase 2D, retinal (GUCY2D); (20) The eye condition is associated with Leber congenital amaurosis type 2 (LCA type 2), and the therapeutic The product is retinoid isomerohydrolase RPE65 (RPE65); (21) The eye condition is associated with LCA 3 and the therapeutic product is associated with spermatogenesis-related 7 (S PATA7); (22) The eye condition is associated with Leber congenital amaurosis-4 (LCA 4), and the therapeutic The 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 The product is reversillin (LCA5); (24) The eye condition is associated with Leber congenital amaurosis-6 (LCA 6), and the therapeutic The product is RPGR-interacting protein 1 (RPGRIP1); (25) The eye condition is associated with Leber congenital amaurosis-7 (LCA 7), and the therapeutic The product is the cone-rod homeobox (CRX); (26) The eye condition is associated with Leber congenital amaurosis-8 (LCA 8), and the therapeutic The product is Crumbs cell polarity complex component 1 (CRB1); (27) The eye condition is associated with Leber congenital amaurosis-9 (LCA 9), and the therapeutic The product is nicotinamide nucleotide adenylyltransferase 1 (NMNAT1) is; (28) The eye condition is associated with Leber congenital amaurosis-10 (LCA 10), and the treatment The therapeutic product is centrosomal protein 290 (CEP290); (29) The eye condition is associated with Leber congenital amaurosis-11 (LCA 11), and the treatment The therapeutic product is inosine monophosphate dehydrogenase 1 (IMPDH1); (30) The eye condition is associated with Leber congenital amaurosis-12 (LCA 12), and the treatment 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 treatment The therapeutic product is retinol dehydrogenase 12 (RDH12); (32) The eye condition is associated with Leber congenital amaurosis-14 (LCA 14), and the treatment The therapeutic product is lecithin retinol acyltransferase (LRAT); (33) The eye condition is associated with Leber congenital amaurosis-15 (LCA 15), and the treatment The therapeutic product is tubby-like protein 1 (TULP1); (34) The eye condition is associated with Leber congenital amaurosis-16 (LCA 16), and the treatment The therapeutic product is a potassium voltage-gated channel subfamily J member 13 (KCNJ13 ) is; (35) The eye condition is associated with Leber's hereditary optic neuropathy (LHON), and the therapeutic product The enzyme is mitochondrially encoded NADH dehydrogenase 1 (MT-ND1). ru; (36) The eye condition is associated with LHON, and the therapeutic product acts on mitochondria. oxidized NADH dehydrogenase 4 (MT-ND4); (37) The eye condition is associated with LHON, and the therapeutic product acts on mitochondria. oxidized NADH dehydrogenase 6 (MT-ND6); (38) The eye condition is associated with neuromyelitis optica (NMO) and the therapeutic product is an anti-complement C5 monoclonal antibody; (39) The eye condition is associated with NMO and the therapeutic product is an anti-IL6 monoclonal antibody. It is an antibody; (40) The eye condition is associated with uveitis, and the therapeutic product is an anti-complement C5 monoclonal antibody. It is a monoclonal 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-1 0 (IL10); (43) The eye condition is associated with uveitis and the therapeutic product is an anti-TNF monoclonal antibody. is a clonal antibody; (44) The eye condition is associated with choroideremia, and the therapeutic product is Love Escort Protein 1 (CHM); (45) The eye condition is associated with X-linked retinoschisis (XLRS) and the therapeutic product comprises: is retinoschisin (RS1); (46) The eye condition is associated with Bardet-Biedl syndrome 1 and the therapeutic product is De-Biedl syndrome 1 (BBS1); (47) The eye condition is associated with Bardet-Biedl syndrome2 and the therapeutic product is De-Biedl syndrome 2 (BBS2); (48) The eye condition is associated with Bardet-Biedl syndrome 3, and the therapeutic product is for treating AD P ribosylation factor-like GTPase6 (ARL6); (49) The eye condition is associated with Bardet-Biedl syndrome4 and the therapeutic product is De-Biedl syndrome 4 (BBS4); (50) The eye condition is associated with Bardet-Biedl syndrome5 and the therapeutic product is De-Biedl syndrome 5 (BBS5); (51) The eye condition is associated with Bardet-Biedl syndrome 6 and the therapeutic product is Muzik-Kaufman syndrome (MKKS); (52) The eye condition is associated with Bardet-Biedl syndrome, and the therapeutic product is De-Biedl syndrome 7 (BBS7); (53) The eye condition is associated with Bardet-Biedl syndrome, and the therapeutic product is tetracycline. is latricopeptide repeat domain 8 (TTC8); (54) The eye condition is associated with Bardet-Biedl syndrome, and the therapeutic product is De-Biedl syndrome 9 (BBS9); (55) The eye condition is associated with Bardet-Biedl syndrome and the therapeutic product is Ruedet-Biedl syndrome 10 (BBS10); (56) The eye condition is associated with Bardet-Biedl syndrome and the therapeutic product is partial motif containing 32 (TRIM32); (57) The eye condition is associated with Bardet-Biedl syndrome12 and the therapeutic product is Ruedet-Biedl syndrome 12 (BBS12); (58) The eye condition is associated with Bardet-Biedl syndrome13 and the therapeutic product is KS transition zone complex subunit 1 (MKS1); (59) The eye condition is associated with Bardet-Biedl syndrome14 and the therapeutic product is is corpus cardiac protein 290 (CEP290); (60) The eye condition is associated with Bardet-Biedl syndrome15 and the therapeutic product is is a D-repeat-containing planar cell polarity effector (WDPCP); (61) The eye condition is associated with Bardet-Biedl syndrome16 and the therapeutic product is serologically defined colon cancer antigen 8 (SDCCAG8); (62) The eye condition is associated with Bardet-Biedl syndrome17 and the therapeutic product is isin zipper transcription factor-like 1 (LZTFL1); (63) The eye condition is associated with Bardet-Biedl syndrome18 and the therapeutic product is is BSome-interacting protein 1 (BBIP1); (64) The eye condition is associated with Bardet-Biedl syndrome and the therapeutic product is Intra-Finger Transport 27 (IFT27); (65) The eye condition is associated with cone dystrophy and the therapeutic product is a guanylic acid cyclase activating factor 1A (GUCA1A); (66) The eye condition is associated with optic nerve atrophy, and the therapeutic product is a mitochondrial protein encoding OPA1 mitochondrion. rear dynamin-like GTPase (OPA1); (67) The eye condition is associated with retinitis pigmentosa 1, and the therapeutic product is an RP1 axoneme microenvironment. are canaliculus-related (RP1); (68) The eye condition is associated with retinitis pigmentosa 2, and the therapeutic product is ARL3 G is the RP2 activator of TPase (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 a pre-mRNA precursor processing factor 31 (PRPF31); (71) The eye condition is associated with retinitis pigmentosa 12 and the therapeutic product is Crumb s cell polarity complex component 1 (CRB1); (72) The eye condition is associated with retinitis pigmentosa 13, and the therapeutic product is a pre-mRNA precursor processing factor 8 (PRPF8); (73) The eye condition is associated with retinitis pigmentosa25 and the therapeutic product is an eye drop. It is a homologue (EYS); (74) The eye condition is associated with retinitis pigmentosa 28 and the therapeutic product is FAM16 1 centrosomal protein A (FAM161A); (75) The eye condition is associated with retinitis pigmentosa37, and the therapeutic product is a nuclear receptor stimulator. N-family 2 group E member 3 (NR2E3); (76) The eye condition is associated with retinitis pigmentosa 38, and the therapeutic product is a MER protein. a tocogene, tyrosine kinase (MERTK); (77) The eye condition is associated with retinitis pigmentosa 40 and the therapeutic product is a phosphodiesterase inhibitor. protease 6B (PDE6B); (78) The eye condition is associated with retinitis pigmentosa 41 and the therapeutic product is prominence 1(PROM1); (79) The eye condition is associated with retinitis pigmentosa 43 and the therapeutic product is a phosphodiesterase inhibitor. protease 6A (PDE6A); (80) The eye condition is associated with retinitis pigmentosa 56, and the therapeutic product is an interphotoreceptor matrix proteoglycan 2 (IMPG2); (81) The eye condition is associated with retinitis pigmentosa 62 and the therapeutic product is administered to male germ cells. is a cytoplasmic associ- ated kinase (MAK); (82) The eye condition is associated with retinitis pigmentosa 80, and the therapeutic product is delivered via intraflagellar transport. 140 (IFT140); (83) The eye condition is associated with dry AMD, and the therapeutic product is an anti-complement C5 monoclonal antibody. It is a monoclonal antibody; (84) The eye condition is associated with dry AMD, and the therapeutic product is an anti-membrane attack complex ( MAC) monoclonal antibodies; (85) The eye condition is associated with dry AMD, and the therapeutic product is a therapeutic agent for treating HtrA serine peptides. putidase 1 (HTRA1); (86) The eye condition is associated with Best's disease and the therapeutic product is bestrophin 1 (B EST1); (87) The eye condition is associated with dry AMD, and the therapeutic product is a complement factor B anti-inflammatory drug. is a sense oligonucleotide; (88) The eye condition is associated with dry AMD and the therapeutic product is an anti-beta-amylo It is an id monoclonal antibody; (89) The eye condition is associated with dry AMD, and the therapeutic product is a compound that inhibits the CD59 glycoprotein. protein (CD59); (90) The eye condition is associated with dry AMD, and the therapeutic product is a channelrhodopsin inhibitor. ChR1; (91) The eye condition is associated with dry AMD, and the therapeutic product is a channelrhodopsin inhibitor. Chlamydomonas reinhardti It is a light-sensitive protein discovered in i; (92) The eye condition is associated with dry AMD, and the therapeutic product is an anti-complement factor C5a It is an aptamer; (93) The eye condition is associated with dry AMD, and the therapeutic product is an anti-complement factor D monoclonal antibody. It is a clonal antibody; (94) The eye pathology is associated with age-related retinal ganglion cell (RGC) degeneration, and the treatment The product is the DnaJ heat shock protein family (Hsp40) member C3( DNAJC3); (95) The eye condition is associated with blue-cone monochromatism (BCM) and the therapeutic product is is opsin (OPN1LW); (96) The eye condition is associated with glaucoma, and the therapeutic product is beta-2 adrenaline. receptor siRNA; (97) The eye condition is associated with glaucoma, and the therapeutic product is a compound that inhibits caspase-2 (CAS P2); (98) The eye condition is associated with glaucoma, and the therapeutic product is an insulin receptor substrate 1. (IRS1); (99) The eye condition is associated with glaucoma, and the therapeutic product is a compound that inhibits HIF-1 responsive proteins. Protein RTP801 (RTP801); (100) The eye condition is associated with glaucoma, and the therapeutic product is a transforming Growth factor beta 2 (TGFB2); (101) The eye condition is associated with glaucoma, and the therapeutic product is a brain-derived neurotrophic factor ( BDNF); (102) The eye condition is associated with glaucoma, and the therapeutic product is a ciliary neurotrophic factor ( CNTF); (103) The eye condition is associated with glaucoma, and the therapeutic product is a prostaglandin- endoperoxide synthase 2 (PTGS2); (104) The eye condition is associated with glaucoma, and the therapeutic product is prostaglandin F receptor (PTGFR); (105) The eye condition is associated with glaucoma, and the therapeutic product is hyaluronidase. ru; (106) The eye condition is associated with glaucoma, and the therapeutic product is a pigment epithelium-derived factor (P EDF); (107) The eye condition is associated with glaucoma, and the therapeutic product is a vascular endothelial growth factor (VGF). EGF); (108) The eye condition is associated with glaucoma, and the therapeutic product is placental growth factor (PGF ) is; (109) The eye condition is associated with glaucoma, and the therapeutic product is a compound selected from the group consisting of myocilin (MYOC) and erythrocyte serine monophosphate (ECN). ) is; (110) The eye condition is associated with NMO and the therapeutic product is an anti-complement C5 monoclonal antibody. is a clonal antibody; (111) The eye condition is associated with NMO, and the therapeutic product is a CC motif chemokine. CCR5 siRNA; (112) The eye condition is associated with NMO and the therapeutic product is an anti-CD19 monoclonal antibody. is a clonal antibody; (113) The eye condition is associated with retinitis pigmentosa associated with a rhodopsin mutation, and the treatment The therapeutic product is channelrhodopsin-1 (ChR1); (114) The eye condition is associated with retinitis pigmentosa associated with a rhodopsin mutation, and the treatment The therapeutic product is channelrhodopsin-2 (ChR2); (115) The eye condition is associated with retinitis pigmentosa, and the therapeutic product is a ciliary nerve growth inhibitor. nutrient factor (CNTF); (116) The eye condition is associated with autosomal recessive retinitis pigmentosa, and the therapeutic product comprises: Crumbs cell polarity complex component 1 (CRB1); (117) The eye condition is associated with autosomal recessive retinitis pigmentosa, and the therapeutic product comprises: Crumbs cell polarity complex component 2 (CRB2); (118) The eye condition is associated with retinitis pigmentosa, and the therapeutic product is a histone deacetylase inhibitor. is acetyltransferase 4 (HDAC4); (119) The eye condition is associated with retinitis pigmentosa and the therapeutic product is rhodopsin ( RHO); (120) The eye condition is associated with retinitis pigmentosa, and the therapeutic product is a nerve growth factor (NGF)- (NGF); (121) The eye condition is associated with retinitis pigmentosa, and the therapeutic product is a nuclear factor, red blood cell is globule 2-like 2 (NRF2); (122) The eye condition is associated with retinitis pigmentosa, and the therapeutic product is a pigment epithelium-derived factor (PEDF); (123) The eye condition is associated with retinitis pigmentosa, and the therapeutic product is glutathione is S-transferase PI1 (GSTP1); (124) The eye condition is associated with retinitis pigmentosa, and the therapeutic product is a rod-cone derivative. is a survival 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 retinaldehyde. hydrid-binding protein 1 (RLBP1); (127) The eye condition is associated with Stargardt's disease, and the therapeutic product is an anti-complement C5 It is an aptamer; (128) The eye condition is associated with uveitis and the therapeutic product is a double homeobox. DUX4; (129) The eye condition is associated with uveitis, and the therapeutic product is a compound selected from the group consisting of NLR family members. 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 a corticotropin-releasing hormone (ACH). Mon (ACTH); (132) The eye condition is associated with uveitis, and the therapeutic product is a compound that inhibits caspase 1(C ASP1); (133) The eye condition is associated with uveitis, and the therapeutic product is an anti-CD59 monoclonal antibody. It is a monoclonal antibody; (134) The eye condition is associated with uveitis, and the therapeutic product is an anti-complement C5 aptamer. Being Ma; (135) The eye condition is associated with corneal neovascularization, and the therapeutic product is an insulin receptor inhibitor. isotopic matrix 1 (IRS1); (136) The eye condition is associated with corneal neovascularization, and the therapeutic product is a NOTCH-regulated ankyrin repeat protein (NRARP); (137) The eye condition is associated with diabetic retinopathy, and the therapeutic product is a product of the NOTCH system. Regulatory ankyrin repeat proteins (NRARPs); (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 activator. Gen (PLG); (140) The eye condition is associated with diabetic retinopathy and the therapeutic product is a growth hormone is; (141) The eye condition is associated with diabetic retinopathy and the therapeutic product is an insulin-like Growth factor 1 (IGF1); (142) The eye condition is associated with diabetic retinopathy and the therapeutic product is an interleukin (IL)-1. It is IL1B. (143) The eye condition is associated with diabetic retinopathy and the therapeutic product is angiotensin II. Syn I converting enzyme 2 (ACE2); (144) The eye condition is associated with diabetic retinopathy and the therapeutic product is IRS1. ru; (145) The eye condition is associated with diabetic retinopathy and the therapeutic product is an anti-integrin It is an 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, and the therapeutic product is an anti-CD40 monoclonal antibody. monoclonal antibodies; (148) The eye condition is associated with Graves' ophthalmopathy, and the therapeutic product is an anti-insulin It is an IGF-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 It is an IGF-like growth factor 2 receptor (IGF2R) monoclonal antibody; (150) The eye condition is associated with DME and the therapeutic product is an anti-integrin oligonucleotide. It is a peptide; (151) The eye condition is associated with DME and the therapeutic product is an anti-placental growth factor (PG F) is a monoclonal antibody; (152) The eye condition is associated with DME, and the therapeutic product is RTP801 siR Being NA; (153) The eye condition is associated with multiple sclerosis (MS)-related vision loss, and the therapeutic The product is ND1; (154) The eye condition is associated with myopia, and the therapeutic product is a matrix metalloproteinase. Methamylase 2 (MMP2) RNAi; (155) The eye condition is associated with X-linked recessive ocular albinism, and the therapeutic product is a G protein Protein-coupled receptor 143 (GPR143); (156) The eye condition is associated with oculocutaneous albinism type 1 and the therapeutic product is tyrosine Ze (TYR); (157) The eye condition is associated with optic neuritis and the therapeutic product inhibits caspase 2 (CA SP2); (158) The eye condition is associated with optic neuritis, and the therapeutic product is an anti-leucine-rich Peat and Ig domain-containing protein 1 (LINGO1) monoclonal antibody; or (159) The ocular condition is associated with polypoidal choroidal vasculopathy, and the therapeutic product is an anti-coagulant. 19. The method of any one of paragraphs 1 to 11 and 13 to 18, wherein the antibody is a C5 aptamer. 27. (1) The eye condition is associated with X-linked retinitis pigmentosa (XLRP), and the therapeutic The product is retinitis pigmentosa GTPase regulator (RPGR); (2) The eye condition is associated with color vision deficiency (ACHM) and the therapeutic product is a circular nucleic acid. is the octide-gated channel beta 3 (CNGB3); (3) The eye condition is associated with color vision deficiency, and the therapeutic product is a cyclic nucleotide gate. Channel Alpha 3 (CNGA3); or (4) The eye condition is associated with biallelic RPE65 mutation-associated retinal dystrophy. and wherein the therapeutic product is retinoid isomerohydrolase RPE65 (RPE65). The method according to any one of paragraphs 1 to 11 and 15 to 18. 28. (1) The eye condition is associated with Batten-CLN1, and the therapeutic product is a palmitoyltransferase. toil-protein thioesterase 1 (PPT1); (2) the ocular condition is associated with Batten-CLN2 and the therapeutic product is a tripeptide le-peptidase 1 (TPP1); (3) The pathology of the eye is associated with Batten-CLN3, and the therapeutic product is a battenin ( CLN3); (4) The ocular condition is associated with uveitis, and the therapeutic product is an anti-interleukin-6 (IL6) monoclonal antibody; (5) The ocular condition is associated with uveitis and the therapeutic product is an anti-TNF alpha (T NF) is a monoclonal antibody; (6) The ocular condition is associated with diabetic macular edema (DME) and the therapeutic product is an anti-I L6 is a monoclonal antibody; (7) The eye condition is associated with red-green color blindness, and the therapeutic product is a compound selected from the group consisting of L opsin (OPN1L) and L opsin (OPN1L). W); (8) The eye condition is associated with red-green color blindness, and the therapeutic product is a compound selected from the group consisting of M opsin (OPN1M W); (9) The ocular condition is associated with blue-cone monochromatism, and the therapeutic product is a compound that inhibits M opsin (O PN1MW); (10) The eye condition is associated with Leber congenital amaurosis-1 (LCA-1), and the therapeutic The product is guanylate cyclase 2D, retinal (GUCY2D); (11) The eye condition is associated with Leber congenital amaurosis type 2 (LCA type 2), and the therapeutic The product is retinoid isomerohydrolase RPE65 (RPE65); (12) The eye condition is associated with Leber congenital amaurosis-7 (LCA 7), and the therapeutic The product is the cone-rod homeobox (CRX); (13) The eye condition is associated with Leber congenital amaurosis-11 (LCA 11), and the treatment The therapeutic product is inosine monophosphate dehydrogenase 1 (IMPDH1); (14) The eye condition is associated with Leber congenital amaurosis-12 (LCA 12), and the treatment The therapeutic product is retinal degeneration 3, GUCY2D regulator (RD3); (15) The eye condition is associated with Leber congenital amaurosis-13 (LCA 13), and the treatment The therapeutic product is retinol dehydrogenase 12 (RDH12); (16) The eye condition is associated with Leber congenital amaurosis-15 (LCA 15), and the treatment The therapeutic product is tubby-like protein 1 (TULP1); (17) The eye condition is associated with Leber congenital amaurosis-16 (LCA 16), and the treatment The therapeutic product is a potassium voltage-gated channel subfamily J member 13 (KCNJ13 ) is; (18) The eye condition is associated with Leber's hereditary optic neuropathy (LHON), and the therapeutic product The enzyme is mitochondrially encoded NADH dehydrogenase 1 (MT-ND1). ru; (19) The eye condition is associated with LHON, and the therapeutic product acts on mitochondria. oxidized NADH dehydrogenase 4 (MT-ND4); (20) The eye condition is associated with LHON, and the therapeutic product acts on mitochondria. oxidized NADH dehydrogenase 6 (MT-ND6); (21) The eye condition is associated with neuromyelitis optica (NMO) and the therapeutic product is an anti-complement C5 monoclonal antibody; (22) The eye condition is associated with NMO and the therapeutic product is an anti-IL6 monoclonal antibody. It is an antibody; (23) The eye condition is associated with uveitis, and the therapeutic product is an anti-complement C5 monoclonal antibody. It is a monoclonal antibody; (24) The eye condition is associated with uveitis and the therapeutic product is angiotensin I converting enzyme (ACE); (25) The eye condition is associated with uveitis, and the therapeutic product is interleukin-1 0 (IL10); (26) The eye condition is associated with uveitis and the therapeutic product is an anti-TNF monoclonal antibody. is a clonal antibody; (27) The eye condition is associated with X-linked retinoschisis (XLRS) and the therapeutic product comprises: is retinoschisin (RS1); (28) The eye condition is associated with Bardet-Biedl syndrome 1 and the therapeutic product is De-Biedl syndrome 1 (BBS1); (29) The eye condition is associated with Bardet-Biedl syndrome 3, and the therapeutic product is for treating AD P ribosylation factor-like GTPase6 (ARL6); (30) The eye condition is associated with Bardet-Biedl syndrome 5 and the therapeutic product is De-Biedl syndrome 5 (BBS5); (31) The eye condition is associated with Bardet-Biedl syndrome 6 and the therapeutic product is Muzik-Kaufman syndrome (MKKS); (32) The eye condition is associated with Bardet-Biedl syndrome and the therapeutic product is Ruedet-Biedl syndrome 10 (BBS10); (33) The eye condition is associated with Bardet-Biedl syndrome and the therapeutic product is partial motif containing 32 (TRIM32); (34) The eye condition is associated with Bardet-Biedl syndrome 13 and the therapeutic product is KS transition zone complex subunit 1 (MKS1); (35) The eye condition is associated with Bardet-Biedl syndrome 18 and the therapeutic product is B is BSome-interacting protein 1 (BBIP1); (36) The eye condition is associated with Bardet-Biedl syndrome and the therapeutic product is Intra-Finger Transport 27 (IFT27); (37) The eye condition is associated with cone dystrophy and the therapeutic product is a guanylic acid cyclase activating factor 1A (GUCA1A); (38) The eye condition is associated with retinitis pigmentosa 13, and the therapeutic product is a pre-mRNA precursor processing factor 8 (PRPF8); (39) The eye condition is associated with retinitis pigmentosa37, and the therapeutic product is a nuclear receptor stimulator. is a member of the N-terminal family 2 group E (NR2E3); or (40) The eye condition is associated with Best's disease and the therapeutic product is bestrophin 1 (B EST1). 29. (1) The eye condition is biallelic RPE65 mutation-associated retinal dystrophy The present invention relates to a method for treating retinoid isomerohydrolase RPE65 (RPE65), 19. The method of any one of paragraphs 1 to 11 and 15 to 18, wherein 30. (1) The eye condition is associated with Batten-CLN2, and the therapeutic product is a tripe putidyl-peptidase 1 (TPP1); (2) the eye condition is associated with Usher syndrome type 1 and the therapeutic product is myosin V IIA (MYO7A); (3) The eye condition is associated with Usher syndrome type 1, and the therapeutic product is a cadherin Related 23 (CDH23); (4) The eye condition is associated with Usher syndrome type 2, and the therapeutic product is a protococcid. Helin-related 15 (PCDH15); (5) The eye condition is associated with Usher syndrome type 2, and the therapeutic product is phosphorus (USH2A); (6) The eye condition is associated with Usher syndrome type 3, and the therapeutic product is Curaline 1. (CLRN1); (7) The eye condition is associated with Stargardt's disease, and the therapeutic product is an ATP-binding cascade. ABCA4; (8) The eye condition is associated with Stargardt's disease and the therapeutic product is ELOVL fat acid elongase 4 (ELOVL4); (9) The eye condition is associated with red-green color blindness, and the therapeutic product is a compound selected from the group consisting of L opsin (OPN1L) and L opsin (OPN1L). W); (10) The eye condition is associated with red-green color blindness, and the therapeutic product is a compound that inhibits M opsin (OPN1 MW); (11) The eye condition is associated with blue-cone monochromatism, and the therapeutic product is a compound that inhibits M opsin ( OPN1MW); (12) The eye condition is associated with Leber congenital amaurosis-1 (LCA 1), and the therapeutic The product is guanylate cyclase 2D, retinal (GUCY2D); (13) The eye condition is associated with Leber congenital amaurosis type 2 (LCA type 2), and the therapeutic The product is retinoid isomerohydrolase RPE65 (RPE65); (14) The eye condition is associated with Leber congenital amaurosis-4 (LCA 4), and the therapeutic The product is aryl hydrocarbon receptor-interacting protein-like 1 (AIPL1); (15) The eye condition is associated with Leber congenital amaurosis-7 (LCA 7), and the therapeutic The product is the cone-rod homeobox (CRX); (16) The eye condition is associated with Leber congenital amaurosis-8 (LCA 8), and the therapeutic The product is Crumbs cell polarity complex component 1 (CRB1); (17) The eye condition is associated with Leber congenital amaurosis-9 (LCA 9), and the therapeutic The product is nicotinamide nucleotide adenylyltransferase 1 (NMNAT1) is; (18) The eye condition is associated with Leber congenital amaurosis-10 (LCA 10), and the treatment The therapeutic product is centrosomal protein 290 (CEP290); (19) The eye condition is associated with Leber congenital amaurosis-11 (LCA 11), and the treatment The therapeutic product is inosine monophosphate dehydrogenase 1 (IMPDH1); (20) The eye condition is associated with Leber congenital amaurosis-15 (LCA 15), and the treatment The therapeutic product is tubby-like protein 1 (TULP1); (21) The eye condition is associated with LHON, and the therapeutic product acts on mitochondria. oxidized NADH dehydrogenase 4 (MT-ND4); (22) The eye condition is associated with LHON, and the therapeutic product acts on mitochondria. oxidized NADH dehydrogenase 6 (MT-ND6); (23) The eye condition is associated with choroideremia, and the therapeutic product is Love Escort Protein 1 (CHM); (24) The eye condition is associated with X-linked retinoschisis (XLRS) and the therapeutic product is is retinoschisin (RS1); (25) The eye condition is associated with Bardet-Biedl syndrome 1 and the therapeutic product is De-Biedl syndrome 1 (BBS1); (26) The eye condition is associated with Bardet-Biedl syndrome 6 and the therapeutic product is Muzik-Kaufman syndrome (MKKS); (27) The eye condition is associated with Bardet-Biedl syndrome and the therapeutic product is Ruedet-Biedl syndrome 10 (BBS10); (28) The eye condition is associated with cone dystrophy and the therapeutic product is a guanylic acid cyclase activating factor 1A (GUCA1A); (29) The eye condition is associated with optic nerve atrophy, and the therapeutic product is a mitochondrial protein encoding OPA1 mitochondrion. rear dynamin-like GTPase (OPA1); (30) The eye condition is associated with retinitis pigmentosa 1, and the therapeutic product is an RP1 axoneme microenvironment. are canaliculus-related (RP1); (31) The eye condition is associated with retinitis pigmentosa 2, and the therapeutic product is ARL3 G is the RP2 activator of TPase (RP2); (32) The eye condition is associated with retinitis pigmentosa 7 and the therapeutic product is peripherin 2 (PRPH2); (33) The eye condition is associated with retinitis pigmentosa 11, and the therapeutic product is a pre-mRNA precursor processing factor 31 (PRPF31); (34) The eye condition is associated with retinitis pigmentosa 13, and the therapeutic product is a pre-mRNA precursor processing factor 8 (PRPF8); (35) The eye condition is associated with retinitis pigmentosa37, and the therapeutic product is a nuclear receptor stimulator. N-family 2 group E member 3 (NR2E3); (36) The eye condition is associated with retinitis pigmentosa 38, and the therapeutic product is a MER protein. a tocogene, tyrosine kinase (MERTK); (37) The eye condition is associated with retinitis pigmentosa 40 and the therapeutic product is a phosphodiesterase inhibitor. protease 6B (PDE6B); (38) The eye condition is associated with retinitis pigmentosa 41 and the therapeutic product is prominence 1(PROM1); (39) The eye condition is associated with retinitis pigmentosa 56, and the therapeutic product is an interphotoreceptor matrix proteoglycan 2 (IMPG2); (40) The eye condition is associated with retinitis pigmentosa 62 and the therapeutic product is administered to male germ cells. is a cytoplasmic associ- ated kinase (MAK); (41) The eye condition is associated with retinitis pigmentosa 80, and the therapeutic product is delivered via intraflagellar transport. 140 (IFT140); or (42) The eye condition is associated with Best's disease, and the therapeutic product is bestrophin 1 (B EST1). 31. (1) The eye condition is associated with X-linked retinitis pigmentosa (XLRP), and the therapeutic The product is retinitis pigmentosa GTPase regulator (RPGR); (2) the eye condition is associated with color vision deficiency, and the therapeutic product is a cyclic nucleotide gate Channel beta 3 (CNGB3); or (3) The eye condition is associated with color vision deficiency, and the therapeutic product is a cyclic nucleotide gate. Any one of paragraphs 1 to 11 and 15 to 18, which is Channel Alpha 3 (CNGA3) The method described below. 32. The recombinant viral vector comprises a promoter or an enhancer-promoter and further comprising a nucleotide sequence encoding said promoter or enhancer-protein. The nucleotide sequence encoding the promoter is a promoter or enhancer-promoter operably linked to a nucleotide sequence, (1) CAG promoter; (2) CBA promoter; (3) CMV promoter; (4) PR1.7 promoter; (5) rhodopsin kinase (GRK1) photoreceptor-specific enhancer-promoter; (6) hCARp promoter; (7)hRKp; (8) cone photoreceptor-specific human arrestin 3 (ARR3) promoter; (9) rhodopsin promoter; or (10) The method according to any one of paragraphs 1 to 31, wherein the promoter is a U6 promoter. 33. The recombinant viral vector comprises a nucleotide sequence encoding a cone-specific promoter. and the nucleotide sequence encoding the cone-specific promoter is operably linked to said nucleotide sequence encoding the therapeutic product, (1) The eye condition is associated with red-green color blindness, and the therapeutic product is a compound that inhibits L opsin (OPN1L W); (2) the eye condition is associated with red-green color blindness, and the therapeutic product is a compound that inhibits M opsin (OPN1M W); (3) The ocular condition is associated with blue-cone monochromatism, and the therapeutic product is a phosphodiesterase (MOP)-dependent ... PN1MW); (4) The eye condition is associated with cone dystrophy and the therapeutic product is a guanylate synthase. is a glucose-activating factor 1A (GUCA1A); or (5) The eye condition is associated with blue-cone monochromatism (BCM), and the therapeutic product is The method according to any one of paragraphs 1 to 11 and 13 to 15, wherein the antibody is pSin (OPN1LW). Law. 34. The administering step delivers a therapeutically effective amount of the therapeutic product to the retina of the human subject. , The method according to any one of paragraphs 1 to 33. 35. The therapeutically effective amount of the therapeutic product is produced by human retinal cells of the human subject. 35. The method of paragraph 34, wherein 36. The therapeutically effective amount of the therapeutic product is administered to the human subject in the form of human photoreceptor cells, horizontal cells, or the like. , bipolar cells, amacrine cells, retinal ganglion cells, and / or retinal pigment epithelial cells of the outer limiting membrane 35. The method of paragraph 34, wherein the antibody is produced by a cell. 37. The method of paragraph 36, wherein the human photoreceptor cells are cone cells and / or rod cells. How to do it. 38. The retinal ganglion cells are midget cells, parasol cells, bilayered cells, giant retinal ganglion cells. 37. The method of paragraph 36, wherein the cells are ganglion cells, photosensitive ganglion cells, and / or Müller glia. . 39. Any of paragraphs 1 to 38, wherein the recombinant viral vector is an rAAV vector. 1. The method according to claim 1. 40. The method of paragraph 39, wherein the recombinant viral vector is an rAAV8 vector. Law. 41. After the administration step, an infrared thermal camera is used to monitor the post-ocular injection of the substance injected into the eye. 41. The method of claim 1, further comprising monitoring the thermal profile of How to do it. 42. The method described in paragraph 41, wherein the infrared thermal camera is a FLIR T530 infrared thermal camera. How to post. 43. The recombinant nucleotide expression vector is about 6.0 x 10 10 Genome copies / eye 44. The method of any one of paragraphs 1 to 43, wherein the dose is administered in a single dose. 44. The recombinant nucleotide expression vector is about 1.6 x 10 11 Genome copies / eye 44. The method of any one of paragraphs 1 to 43, wherein the dose is administered in a single dose. 45. The recombinant nucleotide expression vector is about 2.5 x 10 11 Genome copies / eye 44. The method of any one of paragraphs 1 to 43, wherein the dose is administered in a single dose. 46. ​​The recombinant nucleotide expression vector is about 5.0 x 10 11 Genome copies / eye 44. The method of any one of paragraphs 1 to 43, wherein the dose is administered in a single dose. 47. The recombinant nucleotide expression vector is about 3.0 x 10 12 Genome copies / eye 44. The method of any one of paragraphs 1 to 43, wherein the dose is administered in a single dose. 4.1.2 Set 2 1. A method for treating an ocular condition, comprising: by administering to the animal a recombinant viral vector containing a nucleotide sequence encoding a therapeutic product. expressing said therapeutic product to provide treatment for said ocular condition, The method does not include performing a vitrectomy on the eye. 2. The administering step comprises administering to the subretinal space of the eye of the human subject and to the suprachoroidal space of the eye of the human subject. 2. The method of paragraph 1, comprising administering the recombinant viral vector therapeutic product via Law. 3. The administration step can be inserted into the suprachoroidal space and passed through the suprachoroidal space toward the posterior pole. and the use of a subretinal drug delivery device comprising a catheter with a fine needle for injection into the subretinal space at the posterior pole. 3. The method of claim 2, wherein the method is 4. The administering step includes inserting the catheter of the subretinal drug delivery device into the suprachoroidal space. 4. The method of paragraph 3, comprising: 5. A method for treating an ocular condition, comprising: depositing a suprachoroidal layer on the eye of a human subject in need of treatment. and administering to the cavity a recombinant viral vector containing a nucleotide sequence encoding a therapeutic product. to express said therapeutic product to provide treatment for said ocular condition. 6. The administration step delivers the recombinant viral vector to the suprachoroidal space for suprachoroidal drug delivery. 6. The method of paragraph 5, wherein the method is by injection using a device. 7. Paragraphs 5 or 6, wherein the suprachoroidal drug delivery device is a microinjector. The method described below. 8. A method for treating an ocular condition, comprising: applying a vitreous substance to the outer sclera of the eye of a human subject in need of treatment. The recombinant viral vector containing a nucleotide sequence encoding a therapeutic product is administered to the lateral surface of the administering the therapeutic product to the eye to effect treatment of the eye condition. Law. 9. The administration step involves inserting the tip of the cannula into the scleral surface and bringing it into direct apposition with the scleral surface. by use of a juxtascleral drug delivery device including a cannula capable of 8. The method according to claim 8. 10. The administration step includes inserting the tip of the cannula onto the scleral surface and applying the cannula onto the scleral surface. 10. The method of paragraph 9, comprising direct juxtaposition. 11. Paragraph 1, wherein the therapeutic product is not an anti-human vascular endothelial growth factor (hVEGF) antibody. The method according to any one of claims 1 to 10. 12. The eye condition is not related to neovascular age-related macular degeneration (nAMD), 12. The method according to any one of claims 11 to 11. 13. A method for treating an ocular condition, comprising: depositing a subretinal patch on the eye of a human subject in need of treatment. and administering to the cavity a recombinant viral vector containing a nucleotide sequence encoding a therapeutic product. and expressing said therapeutic product to provide treatment for said condition of the eye, performing a vitrectomy on the subject's eye, wherein the therapeutic product is an anti-human vascular endothelial growth factor (hVEGF) The method, wherein the antibody is not a VEGF antibody. 14. The method of paragraph 13, wherein the vitrectomy is a partial vitrectomy. 15. A method for treating an ocular condition, comprising: positioning a retinal patch in the posterior segment of the eye of a human subject in need of treatment; The nucleic acid encoding the therapeutic product is delivered to the subretinal space around the optic disc, fovea, and macula. a recombinant viral vector containing a nucleotide sequence to express the therapeutic product and induce providing treatment for said condition, comprising performing a vitrectomy on the eye of said human patient. Not the above method. 16. The method of paragraph 15, wherein the administering step is by intravitreal injection. 17. The transvitreal injection is performed by inserting a sharp needle into the sclera via the upper or lower eye side, The virus is then allowed to completely pass through the vitreous body, and the recombinant viral vector is injected into the subretinal space on the opposite side. 17. The method of paragraph 16, comprising: 18. The transvitreal injection is performed by inserting a trocar into the sclera, inserting a cannula into the trocar, and and injecting the recombinant viral vector into the contralateral subretinal space via the retina. 17. The method according to paragraph 16. 19. The method of any one of paragraphs 15 to 18, wherein the therapeutic product is an anti-hVEGF antibody. How to post. 20. The method of paragraph 19, wherein the anti-hVEGF antibody is an anti-hVEGF antigen-binding fragment. The method described. 21. The anti-hVEGF antigen-binding fragment is Fab, F(ab')2, or a single antibody. 21. The method of paragraph 20, wherein the antibody is a fragment chain variable (scFv). 22. The anti-hVEGF antibody has 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. 10. The method according to any one of claims 1 to 9. 23. The anti-hVEGF antibody comprises light chain CDRs 1 to 3 of SEQ ID NOs: 14 to 16 and CDRs 1 to 3 of SEQ ID NOs: 15 to 17. Paragraph 19, which contains heavy chain CDRs 1-3 of SEQ ID NOs. 17-19 or SEQ ID NOs. 20, 18, and 21. The method according to any one of claims 1 to 21. 24. The eye condition is nAMD, dry age-related macular degeneration (dry AMD), retinal vein associated with recurrent retinal occlusion (RVO), diabetic macular edema (DME), or diabetic retinopathy (DR) The method according to any one of paragraphs 19 to 23, 25. The method according to any one of paragraphs 19 to 23, wherein the eye condition is associated with nAMD. Law. 26. (1) The eye condition is associated with Batten-CLN1, and the therapeutic product is a palmitoyltransferase. toil-protein thioesterase 1 (PPT1); (2) the ocular condition is associated with Batten-CLN2 and the therapeutic product is a tripeptide le-peptidase 1 (TPP1); (3) The pathology of the eye is associated with Batten-CLN3, and the therapeutic product is a battenin ( CLN3); (4) the ocular condition is associated with Batten-CLN6, and the therapeutic product is a CLN6 transmembrane a common ER protein (CLN6); (5) The eye condition is associated with Batten-CLN7, and the therapeutic product is a major fasciculation. is tator superfamily domain containing 8 (MFSD8); (6) The eye condition is associated with Usher syndrome type 1, and the therapeutic product is myosin V IIA (MYO7A); (7) The eye condition is associated with Usher syndrome type 1, and the therapeutic product is a cadherin Related 23 (CDH23); (8) The eye condition is associated with Usher syndrome type 2, and the therapeutic product is a protococcid. Helin-related 15 (PCDH15); (9) The eye condition is associated with Usher syndrome type 2, and the therapeutic product is phosphorus (USH2A); (10) The eye condition is associated with Usher syndrome type 3 and the therapeutic product is clarinet. 1 (CLRN1); (11) The eye condition is associated with Stargardt's disease, and the therapeutic product is an ATP-binding protein. Set subfamily A member 4 (ABCA4); (12) The eye condition is associated with Stargardt's disease and the therapeutic product is ELOVL lipid. fatty acid elongase 4 (ELOVL4); (13) The ocular condition is associated with uveitis and the therapeutic product is an anti-interleukin (AIL)-1 inhibitor. 6 (IL6) monoclonal antibody; (14) The eye condition is associated with uveitis and the therapeutic product is an anti-TNF alpha ( TNF) monoclonal antibodies; (15) The eye condition is associated with diabetic macular edema (DME), and the therapeutic product is an anti- It is an IL6 monoclonal antibody; (16) The eye condition is associated with red-green color blindness, and the therapeutic product is a compound that inhibits L-opsin (OPN1 LW); (17) The eye condition is associated with red-green color blindness, and the therapeutic product is a compound that inhibits M opsin (OPN1 MW); (18) The eye condition is associated with blue-cone monochromatism, and the therapeutic product is a compound that inhibits M opsin ( OPN1MW); (19) The eye condition is associated with Leber congenital amaurosis-1 (LCA 1), and the therapeutic The product is guanylate cyclase 2D, retinal (GUCY2D); (20) The eye condition is associated with Leber congenital amaurosis type 2 (LCA type 2), and the therapeutic The product is retinoid isomerohydrolase RPE65 (RPE65); (21) The eye condition is associated with LCA 3 and the therapeutic product is associated with spermatogenesis-related 7 (S PATA7); (22) The eye condition is associated with Leber congenital amaurosis-4 (LCA 4), and the therapeutic The 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 The product is reversillin (LCA5); (24) The eye condition is associated with Leber congenital amaurosis-6 (LCA 6), and the therapeutic The product is RPGR-interacting protein 1 (RPGRIP1); (25) The eye condition is associated with Leber congenital amaurosis-7 (LCA 7), and the therapeutic The product is the cone-rod homeobox (CRX); (26) The eye condition is associated with Leber congenital amaurosis-8 (LCA 8), and the therapeutic The product is Crumbs cell polarity complex component 1 (CRB1); (27) The eye condition is associated with Leber congenital amaurosis-9 (LCA 9), and the therapeutic The product is nicotinamide nucleotide adenylyltransferase 1 (NMNAT1) is; (28) The eye condition is associated with Leber congenital amaurosis-10 (LCA 10), and the treatment The therapeutic product is centrosomal protein 290 (CEP290); (29) The eye condition is associated with Leber congenital amaurosis-11 (LCA 11), and the treatment The therapeutic product is inosine monophosphate dehydrogenase 1 (IMPDH1); (30) The eye condition is associated with Leber congenital amaurosis-12 (LCA 12), and the treatment 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 treatment The therapeutic product is retinol dehydrogenase 12 (RDH12); (32) The eye condition is associated with Leber congenital amaurosis-14 (LCA 14), and the treatment The therapeutic product is lecithin retinol acyltransferase (LRAT); (33) The eye condition is associated with Leber congenital amaurosis-15 (LCA 15), and the treatment The therapeutic product is tubby-like protein 1 (TULP1); (34) The eye condition is associated with Leber congenital amaurosis-16 (LCA 16), and the treatment The therapeutic product is a potassium voltage-gated channel subfamily J member 13 (KCNJ13 ) is; (35) The eye condition is associated with Leber's hereditary optic neuropathy (LHON), and the therapeutic product The enzyme is mitochondrially encoded NADH dehydrogenase 1 (MT-ND1). ru; (36) The eye condition is associated with LHON, and the therapeutic product acts on mitochondria. oxidized NADH dehydrogenase 4 (MT-ND4); (37) The eye condition is associated with LHON, and the therapeutic product acts on mitochondria. oxidized NADH dehydrogenase 6 (MT-ND6); (38) The eye condition is associated with neuromyelitis optica (NMO) and the therapeutic product is an anti-complement C5 monoclonal antibody; (39) The eye condition is associated with NMO and the therapeutic product is an anti-IL6 monoclonal antibody. It is an antibody; (40) The eye condition is associated with uveitis, and the therapeutic product is an anti-complement C5 monoclonal antibody. It is a monoclonal 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-1 0 (IL10); (43) The eye condition is associated with uveitis and the therapeutic product is an anti-TNF monoclonal antibody. is a clonal antibody; (44) The eye condition is associated with choroideremia, and the therapeutic product is Love Escort Protein 1 (CHM); (45) The eye condition is associated with X-linked retinoschisis (XLRS) and the therapeutic product comprises: is retinoschisin (RS1); (46) The eye condition is associated with Bardet-Biedl syndrome 1 and the therapeutic product is De-Biedl syndrome 1 (BBS1); (47) The eye condition is associated with Bardet-Biedl syndrome2 and the therapeutic product is De-Biedl syndrome 2 (BBS2); (48) The eye condition is associated with Bardet-Biedl syndrome 3, and the therapeutic product is for treating AD P ribosylation factor-like GTPase6 (ARL6); (49) The eye condition is associated with Bardet-Biedl syndrome4 and the therapeutic product is De-Biedl syndrome 4 (BBS4); (50) The eye condition is associated with Bardet-Biedl syndrome5 and the therapeutic product is De-Biedl syndrome 5 (BBS5); (51) The eye condition is associated with Bardet-Biedl syndrome 6 and the therapeutic product is Muzik-Kaufman syndrome (MKKS); (52) The eye condition is associated with Bardet-Biedl syndrome, and the therapeutic product is De-Biedl syndrome 7 (BBS7); (53) The eye condition is associated with Bardet-Biedl syndrome, and the therapeutic product is tetracycline. is latricopeptide repeat domain 8 (TTC8); (54) The eye condition is associated with Bardet-Biedl syndrome, and the therapeutic product is De-Biedl syndrome 9 (BBS9); (55) The eye condition is associated with Bardet-Biedl syndrome and the therapeutic product is Ruedet-Biedl syndrome 10 (BBS10); (56) The eye condition is associated with Bardet-Biedl syndrome and the therapeutic product is partial motif containing 32 (TRIM32); (57) The eye condition is associated with Bardet-Biedl syndrome12 and the therapeutic product is Ruedet-Biedl syndrome 12 (BBS12); (58) The eye condition is associated with Bardet-Biedl syndrome13 and the therapeutic product is KS transition zone complex subunit 1 (MKS1); (59) The eye condition is associated with Bardet-Biedl syndrome14 and the therapeutic product is is corpus cardiac protein 290 (CEP290); (60) The eye condition is associated with Bardet-Biedl syndrome15 and the therapeutic product is is a D-repeat-containing planar cell polarity effector (WDPCP); (61) The eye condition is associated with Bardet-Biedl syndrome16 and the therapeutic product is serologically defined colon cancer antigen 8 (SDCCAG8); (62) The eye condition is associated with Bardet-Biedl syndrome17 and the therapeutic product is isin zipper transcription factor-like 1 (LZTFL1); (63) The eye condition is associated with Bardet-Biedl syndrome18 and the therapeutic product is is BSome-interacting protein 1 (BBIP1); (64) The eye condition is associated with Bardet-Biedl syndrome and the therapeutic product is Intra-Finger Transport 27 (IFT27); (65) The eye condition is associated with cone dystrophy and the therapeutic product is a guanylic acid cyclase activating factor 1A (GUCA1A); (66) The eye condition is associated with optic nerve atrophy, and the therapeutic product is a mitochondrial protein encoding OPA1 mitochondrion. rear dynamin-like GTPase (OPA1); (67) The eye condition is associated with retinitis pigmentosa 1, and the therapeutic product is an RP1 axoneme microenvironment. are canaliculus-related (RP1); (68) The eye condition is associated with retinitis pigmentosa 2, and the therapeutic product is ARL3 G is the RP2 activator of TPase (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 a pre-mRNA precursor processing factor 31 (PRPF31); (71) The eye condition is associated with retinitis pigmentosa 12 and the therapeutic product is Crumb s cell polarity complex component 1 (CRB1); (72) The eye condition is associated with retinitis pigmentosa 13, and the therapeutic product is a pre-mRNA precursor processing factor 8 (PRPF8); (73) The eye condition is associated with retinitis pigmentosa25 and the therapeutic product is an eye drop. It is a homologue (EYS); (74) The eye condition is associated with retinitis pigmentosa 28 and the therapeutic product is FAM16 1 centrosomal protein A (FAM161A); (75) The eye condition is associated with retinitis pigmentosa37, and the therapeutic product is a nuclear receptor stimulator. N-family 2 group E member 3 (NR2E3); (76) The eye condition is associated with retinitis pigmentosa 38, and the therapeutic product is a MER protein. a tocogene, tyrosine kinase (MERTK); (77) The eye condition is associated with retinitis pigmentosa 40 and the therapeutic product is a phosphodiesterase inhibitor. protease 6B (PDE6B); (78) The eye condition is associated with retinitis pigmentosa 41 and the therapeutic product is prominence 1(PROM1); (79) The eye condition is associated with retinitis pigmentosa 43 and the therapeutic product is a phosphodiesterase inhibitor. protease 6A (PDE6A); (80) The eye condition is associated with retinitis pigmentosa 56, and the therapeutic product is an interphotoreceptor matrix proteoglycan 2 (IMPG2); (81) The eye condition is associated with retinitis pigmentosa 62 and the therapeutic product is administered to male germ cells. is a cytoplasmic associ- ated kinase (MAK); (82) The eye condition is associated with retinitis pigmentosa 80, and the therapeutic product is delivered via intraflagellar transport. 140 (IFT140); (83) The eye condition is associated with dry AMD, and the therapeutic product is an anti-complement C5 monoclonal antibody. It is a monoclonal antibody; (84) The eye condition is associated with dry AMD, and the therapeutic product is an anti-membrane attack complex ( MAC) monoclonal antibodies; (85) The eye condition is associated with dry AMD, and the therapeutic product is a therapeutic agent for treating HtrA serine peptides. putidase 1 (HTRA1); (86) The eye condition is associated with Best's disease and the therapeutic product is bestrophin 1 (B EST1); (87) The eye condition is associated with dry AMD, and the therapeutic product is a complement factor B anti-inflammatory drug. is a sense oligonucleotide; (88) The eye condition is associated with dry AMD and the therapeutic product is an anti-beta-amylo It is an id monoclonal antibody; (89) The eye condition is associated with dry AMD, and the therapeutic product is a compound that inhibits the CD59 glycoprotein. protein (CD59); (90) The eye condition is associated with dry AMD, and the therapeutic product is a channelrhodopsin inhibitor. ChR1; (91) The eye condition is associated with dry AMD, and the therapeutic product is a channelrhodopsin inhibitor. Chlamydomonas reinhardti It is a light-sensitive protein discovered in i; (92) The eye condition is associated with dry AMD, and the therapeutic product is an anti-complement factor C5a It is an aptamer; (93) The eye condition is associated with dry AMD, and the therapeutic product is an anti-complement factor D monoclonal antibody. It is a clonal antibody; (94) The eye pathology is associated with age-related retinal ganglion cell (RGC) degeneration, and the treatment The product is the DnaJ heat shock protein family (Hsp40) member C3( DNAJC3); (95) The eye condition is associated with blue-cone monochromatism (BCM) and the therapeutic product is is opsin (OPN1LW); (96) The eye condition is associated with glaucoma, and the therapeutic product is beta-2 adrenaline. receptor siRNA; (97) The eye condition is associated with glaucoma, and the therapeutic product is a compound that inhibits caspase-2 (CAS P2); (98) The eye condition is associated with glaucoma, and the therapeutic product is an insulin receptor substrate 1. (IRS1); (99) The eye condition is associated with glaucoma, and the therapeutic product is a compound that inhibits HIF-1 responsive proteins. Protein RTP801 (RTP801); (100) The eye condition is associated with glaucoma, and the therapeutic product is a transforming Growth factor beta 2 (TGFB2); (101) The eye condition is associated with glaucoma, and the therapeutic product is a brain-derived neurotrophic factor ( BDNF); (102) The eye condition is associated with glaucoma, and the therapeutic product is a ciliary neurotrophic factor ( CNTF); (103) The eye condition is associated with glaucoma, and the therapeutic product is a prostaglandin- endoperoxide synthase 2 (PTGS2); (104) The eye condition is associated with glaucoma, and the therapeutic product is prostaglandin F receptor (PTGFR); (105) The eye condition is associated with glaucoma, and the therapeutic product is hyaluronidase. ru; (106) The eye condition is associated with glaucoma, and the therapeutic product is a pigment epithelium-derived factor (P EDF); (107) The eye condition is associated with glaucoma, and the therapeutic product is a vascular endothelial growth factor (VGF). EGF); (108) The eye condition is associated with glaucoma, and the therapeutic product is placental growth factor (PGF ) is; (109) The eye condition is associated with glaucoma, and the therapeutic product is a compound selected from the group consisting of myocilin (MYOC) and erythrocyte serine monophosphate (ECN). ) is; (110) The eye condition is associated with NMO and the therapeutic product is an anti-complement C5 monoclonal antibody. is a clonal antibody; (111) The eye condition is associated with NMO, and the therapeutic product is a CC motif chemokine. CCR5 siRNA; (112) The eye condition is associated with NMO and the therapeutic product is an anti-CD19 monoclonal antibody. is a clonal antibody; (113) The eye condition is associated with retinitis pigmentosa associated with a rhodopsin mutation, and the treatment The therapeutic product is channelrhodopsin-1 (ChR1); (114) The eye condition is associated with retinitis pigmentosa associated with a rhodopsin mutation, and the treatment The therapeutic product is channelrhodopsin-2 (ChR2); (115) The eye condition is associated with retinitis pigmentosa, and the therapeutic product is a ciliary nerve growth inhibitor. nutrient factor (CNTF); (116) The eye condition is associated with autosomal recessive retinitis pigmentosa, and the therapeutic product comprises: Crumbs cell polarity complex component 1 (CRB1); (117) The eye condition is associated with autosomal recessive retinitis pigmentosa, and the therapeutic product comprises: Crumbs cell polarity complex component 2 (CRB2); (118) The eye condition is associated with retinitis pigmentosa, and the therapeutic product is a histone deacetylase inhibitor. is acetyltransferase 4 (HDAC4); (119) The eye condition is associated with retinitis pigmentosa and the therapeutic product is rhodopsin ( RHO); (120) The eye condition is associated with retinitis pigmentosa, and the therapeutic product is a nerve growth factor (NGF)- (NGF); (121) The eye condition is associated with retinitis pigmentosa, and the therapeutic product is a nuclear factor, red blood cell is globule 2-like 2 (NRF2); (122) The eye condition is associated with retinitis pigmentosa, and the therapeutic product is a pigment epithelium-derived factor (PEDF); (123) The eye condition is associated with retinitis pigmentosa, and the therapeutic product is glutathione is S-transferase PI1 (GSTP1); (124) The eye condition is associated with retinitis pigmentosa, and the therapeutic product is a rod-cone derivative. is a survival 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 retinaldehyde. hydrid-binding protein 1 (RLBP1); (127) The eye condition is associated with Stargardt's disease, and the therapeutic product is an anti-complement C5 It is an aptamer; (128) The eye condition is associated with uveitis and the therapeutic product is a double homeobox. DUX4; (129) The eye condition is associated with uveitis, and the therapeutic product is a compound selected from the group consisting of NLR family members. 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 a corticotropin-releasing hormone (ACH). Mon (ACTH); (132) The eye condition is associated with uveitis, and the therapeutic product is a compound that inhibits caspase 1(C ASP1); (133) The eye condition is associated with uveitis, and the therapeutic product is an anti-CD59 monoclonal antibody. It is a monoclonal antibody; (134) The eye condition is associated with uveitis, and the therapeutic product is an anti-complement C5 aptamer. Being Ma; (135) The eye condition is associated with corneal neovascularization, and the therapeutic product is an insulin receptor inhibitor. isotopic matrix 1 (IRS1); (136) The eye condition is associated with corneal neovascularization, and the therapeutic product is a NOTCH-regulated ankyrin repeat protein (NRARP); (137) The eye condition is associated with diabetic retinopathy, and the therapeutic product is a product of the NOTCH system. Regulatory ankyrin repeat proteins (NRARPs); (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 activator. Gen (PLG); (140) The eye condition is associated with diabetic retinopathy and the therapeutic product is a growth hormone is; (141) The eye condition is associated with diabetic retinopathy and the therapeutic product is an insulin-like Growth factor 1 (IGF1); (142) The eye condition is associated with diabetic retinopathy and the therapeutic product is an interleukin (IL)-1. It is IL1B. (143) The eye condition is associated with diabetic retinopathy and the therapeutic product is angiotensin II. Syn I converting enzyme 2 (ACE2); (144) The eye condition is associated with diabetic retinopathy and the therapeutic product is IRS1. ru; (145) The eye condition is associated with diabetic retinopathy and the therapeutic product is an anti-integrin It is an 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, and the therapeutic product is an anti-CD40 monoclonal antibody. monoclonal antibodies; (148) The eye condition is associated with Graves' ophthalmopathy, and the therapeutic product is an anti-insulin It is an IGF-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 It is an IGF-like growth factor 2 receptor (IGF2R) monoclonal antibody; (150) The eye condition is associated with DME and the therapeutic product is an anti-integrin oligonucleotide. It is a peptide; (151) The eye condition is associated with DME and the therapeutic product is an anti-placental growth factor (PG F) is a monoclonal antibody; (152) The eye condition is associated with DME, and the therapeutic product is RTP801 siR Being NA; (153) The eye condition is associated with multiple sclerosis (MS)-related vision loss, and the therapeutic The product is ND1; (154) The eye condition is associated with myopia, and the therapeutic product is a matrix metalloproteinase. Methamylase 2 (MMP2) RNAi; (155) The eye condition is associated with X-linked recessive ocular albinism, and the therapeutic product is a G protein Protein-coupled receptor 143 (GPR143); (156) The eye condition is associated with oculocutaneous albinism type 1 and the therapeutic product is tyrosine Ze (TYR); (157) The eye condition is associated with optic neuritis and the therapeutic product inhibits caspase 2 (CA SP2); (158) The eye condition is associated with optic neuritis, and the therapeutic product is an anti-leucine-rich Peat and Ig domain-containing protein 1 (LINGO1) monoclonal antibody; or (159) The ocular condition is associated with polypoidal choroidal vasculopathy, and the therapeutic product is an anti-coagulant. 19. The method of any one of paragraphs 1 to 11 and 13 to 18, wherein the antibody is a C5 aptamer. 27. (1) The eye condition is associated with X-linked retinitis pigmentosa (XLRP), and the therapeutic The product is retinitis pigmentosa GTPase regulator (RPGR); (2) The eye condition is associated with color vision deficiency (ACHM) and the therapeutic product is a circular nucleic acid. is the octide-gated channel beta 3 (CNGB3); (3) The eye condition is associated with color vision deficiency, and the therapeutic product is a cyclic nucleotide gate. Channel Alpha 3 (CNGA3); or (4) The eye condition is associated with biallelic RPE65 mutation-associated retinal dystrophy. and wherein the therapeutic product is retinoid isomerohydrolase RPE65 (RPE65). The method according to any one of paragraphs 1 to 11 and 15 to 18. 28. (1) The eye condition is associated with Batten-CLN1, and the therapeutic product is a palmitoyltransferase. toil-protein thioesterase 1 (PPT1); (2) the ocular condition is associated with Batten-CLN2 and the therapeutic product is a tripeptide le-peptidase 1 (TPP1); (3) The pathology of the eye is associated with Batten-CLN3, and the therapeutic product is a battenin ( CLN3); (4) The ocular condition is associated with uveitis, and the therapeutic product is an anti-interleukin-6 (IL6) monoclonal antibody; (5) The ocular condition is associated with uveitis and the therapeutic product is an anti-TNF alpha (T NF) is a monoclonal antibody; (6) The ocular condition is associated with diabetic macular edema (DME) and the therapeutic product is an anti-I L6 is a monoclonal antibody; (7) The eye condition is associated with red-green color blindness, and the therapeutic product is a compound selected from the group consisting of L opsin (OPN1L) and L opsin (OPN1L). W); (8) The eye condition is associated with red-green color blindness, and the therapeutic product is a compound selected from the group consisting of M opsin (OPN1M W); (9) The ocular condition is associated with blue-cone monochromatism, and the therapeutic product is a compound that inhibits M opsin (O PN1MW); (10) The eye condition is associated with Leber congenital amaurosis-1 (LCA-1), and the therapeutic The product is guanylate cyclase 2D, retinal (GUCY2D); (11) The eye condition is associated with Leber congenital amaurosis type 2 (LCA type 2), and the therapeutic The product is retinoid isomerohydrolase RPE65 (RPE65); (12) The eye condition is associated with Leber congenital amaurosis-7 (LCA 7), and the therapeutic The product is the cone-rod homeobox (CRX); (13) The eye condition is associated with Leber congenital amaurosis-11 (LCA 11), and the treatment The therapeutic product is inosine monophosphate dehydrogenase 1 (IMPDH1); (14) The eye condition is associated with Leber congenital amaurosis-12 (LCA 12), and the treatment The therapeutic product is retinal degeneration 3, GUCY2D regulator (RD3); (15) The eye condition is associated with Leber congenital amaurosis-13 (LCA 13), and the treatment The therapeutic product is retinol dehydrogenase 12 (RDH12); (16) The eye condition is associated with Leber congenital amaurosis-15 (LCA 15), and the treatment The therapeutic product is tubby-like protein 1 (TULP1); (17) The eye condition is associated with Leber congenital amaurosis-16 (LCA 16), and the treatment The therapeutic product is a potassium voltage-gated channel subfamily J member 13 (KCNJ13 ) is; (18) The eye condition is associated with Leber's hereditary optic neuropathy (LHON), and the therapeutic product The enzyme is mitochondrially encoded NADH dehydrogenase 1 (MT-ND1). ru; (19) The eye condition is associated with LHON, and the therapeutic product acts on mitochondria. oxidized NADH dehydrogenase 4 (MT-ND4); (20) The eye condition is associated with LHON, and the therapeutic product acts on mitochondria. oxidized NADH dehydrogenase 6 (MT-ND6); (21) The eye condition is associated with neuromyelitis optica (NMO) and the therapeutic product is an anti-complement C5 monoclonal antibody; (22) The eye condition is associated with NMO and the therapeutic product is an anti-IL6 monoclonal antibody. It is an antibody; (23) The eye condition is associated with uveitis, and the therapeutic product is an anti-complement C5 monoclonal antibody. It is a monoclonal antibody; (24) The eye condition is associated with uveitis and the therapeutic product is angiotensin I converting enzyme (ACE); (25) The eye condition is associated with uveitis, and the therapeutic product is interleukin-1 0 (IL10); (26) The eye condition is associated with uveitis and the therapeutic product is an anti-TNF monoclonal antibody. is a clonal antibody; (27) The eye condition is associated with X-linked retinoschisis (XLRS) and the therapeutic product comprises: is retinoschisin (RS1); (28) The eye condition is associated with Bardet-Biedl syndrome 1 and the therapeutic product is De-Biedl syndrome 1 (BBS1); (29) The eye condition is associated with Bardet-Biedl syndrome 3, and the therapeutic product is for treating AD P ribosylation factor-like GTPase6 (ARL6); (30) The eye condition is associated with Bardet-Biedl syndrome 5 and the therapeutic product is De-Biedl syndrome 5 (BBS5); (31) The eye condition is associated with Bardet-Biedl syndrome 6 and the therapeutic product is Muzik-Kaufman syndrome (MKKS); (32) The eye condition is associated with Bardet-Biedl syndrome and the therapeutic product is Ruedet-Biedl syndrome 10 (BBS10); (33) The eye condition is associated with Bardet-Biedl syndrome and the therapeutic product is partial motif containing 32 (TRIM32); (34) The eye condition is associated with Bardet-Biedl syndrome 13 and the therapeutic product is KS transition zone complex subunit 1 (MKS1); (35) The eye condition is associated with Bardet-Biedl syndrome 18 and the therapeutic product is B is BSome-interacting protein 1 (BBIP1); (36) The eye condition is associated with Bardet-Biedl syndrome and the therapeutic product is Intra-Finger Transport 27 (IFT27); (37) The eye condition is associated with cone dystrophy and the therapeutic product is a guanylic acid cyclase activating factor 1A (GUCA1A); (38) The eye condition is associated with retinitis pigmentosa 13, and the therapeutic product is a pre-mRNA precursor processing factor 8 (PRPF8); (39) The eye condition is associated with retinitis pigmentosa37, and the therapeutic product is a nuclear receptor stimulator. is a member of the N-terminal family 2 group E (NR2E3); or (40) The eye condition is associated with Best's disease and the therapeutic product is bestrophin 1 (B EST1). 29. (1) The eye condition is biallelic RPE65 mutation-associated retinal dystrophy The present invention relates to a method for treating retinoid isomerohydrolase RPE65 (RPE65), 19. The method of any one of paragraphs 1 to 11 and 15 to 18, wherein 30. (1) The eye condition is associated with Batten-CLN2, and the therapeutic product is a tripe putidyl-peptidase 1 (TPP1); (2) the eye condition is associated with Usher syndrome type 1 and the therapeutic product is myosin V IIA (MYO7A); (3) The eye condition is associated with Usher syndrome type 1, and the therapeutic product is a cadherin Related 23 (CDH23); (4) The eye condition is associated with Usher syndrome type 2, and the therapeutic product is a protococcid. Helin-related 15 (PCDH15); (5) The eye condition is associated with Usher syndrome type 2, and the therapeutic product is phosphorus (USH2A); (6) The eye condition is associated with Usher syndrome type 3, and the therapeutic product is Curaline 1. (CLRN1); (7) The eye condition is associated with Stargardt's disease, and the therapeutic product is an ATP-binding cascade. ABCA4; (8) The eye condition is associated with Stargardt's disease and the therapeutic product is ELOVL fat acid elongase 4 (ELOVL4); (9) The eye condition is associated with red-green color blindness, and the therapeutic product is a compound selected from the group consisting of L opsin (OPN1L) and L opsin (OPN1L). W); (10) The eye condition is associated with red-green color blindness, and the therapeutic product is a compound that inhibits M opsin (OPN1 MW); (11) The eye condition is associated with blue-cone monochromatism, and the therapeutic product is a compound that inhibits M opsin ( OPN1MW); (12) The eye condition is associated with Leber congenital amaurosis-1 (LCA 1), and the therapeutic The product is guanylate cyclase 2D, retinal (GUCY2D); (13) The eye condition is associated with Leber congenital amaurosis type 2 (LCA type 2), and the therapeutic The product is retinoid isomerohydrolase RPE65 (RPE65); (14) The eye condition is associated with Leber congenital amaurosis-4 (LCA 4), and the therapeutic The product is aryl hydrocarbon receptor-interacting protein-like 1 (AIPL1); (15) The eye condition is associated with Leber congenital amaurosis-7 (LCA 7), and the therapeutic The product is the cone-rod homeobox (CRX); (16) The eye condition is associated with Leber congenital amaurosis-8 (LCA 8), and the therapeutic The product is Crumbs cell polarity complex component 1 (CRB1); (17) The eye condition is associated with Leber congenital amaurosis-9 (LCA 9), and the therapeutic The product is nicotinamide nucleotide adenylyltransferase 1 (NMNAT1) is; (18) The eye condition is associated with Leber congenital amaurosis-10 (LCA 10), and the treatment The therapeutic product is centrosomal protein 290 (CEP290); (19) The eye condition is associated with Leber congenital amaurosis-11 (LCA 11), and the treatment The therapeutic product is inosine monophosphate dehydrogenase 1 (IMPDH1); (20) The eye condition is associated with Leber congenital amaurosis-15 (LCA 15), and the treatment The therapeutic product is tubby-like protein 1 (TULP1); (21) The eye condition is associated with LHON, and the therapeutic product acts on mitochondria. oxidized NADH dehydrogenase 4 (MT-ND4); (22) The eye condition is associated with LHON, and the therapeutic product acts on mitochondria. oxidized NADH dehydrogenase 6 (MT-ND6); (23) The eye condition is associated with choroideremia, and the therapeutic product is Love Escort Protein 1 (CHM); (24) The eye condition is associated with X-linked retinoschisis (XLRS) and the therapeutic product is is retinoschisin (RS1); (25) The eye condition is associated with Bardet-Biedl syndrome 1 and the therapeutic product is De-Biedl syndrome 1 (BBS1); (26) The eye condition is associated with Bardet-Biedl syndrome 6 and the therapeutic product is Muzik-Kaufman syndrome (MKKS); (27) The eye condition is associated with Bardet-Biedl syndrome and the therapeutic product is Ruedet-Biedl syndrome 10 (BBS10); (28) The eye condition is associated with cone dystrophy and the therapeutic product is a guanylic acid cyclase activating factor 1A (GUCA1A); (29) The eye condition is associated with optic nerve atrophy, and the therapeutic product is a mitochondrial protein encoding OPA1 mitochondrion. rear dynamin-like GTPase (OPA1); (30) The eye condition is associated with retinitis pigmentosa 1, and the therapeutic product is an RP1 axoneme microenvironment. are canaliculus-related (RP1); (31) The eye condition is associated with retinitis pigmentosa 2, and the therapeutic product is ARL3 G is the RP2 activator of TPase (RP2); (32) The eye condition is associated with retinitis pigmentosa 7 and the therapeutic product is peripherin 2 (PRPH2); (33) The eye condition is associated with retinitis pigmentosa 11, and the therapeutic product is a pre-mRNA precursor processing factor 31 (PRPF31); (34) The eye condition is associated with retinitis pigmentosa 13, and the therapeutic product is a pre-mRNA precursor processing factor 8 (PRPF8); (35) The eye condition is associated with retinitis pigmentosa37, and the therapeutic product is a nuclear receptor stimulator. N-family 2 group E member 3 (NR2E3); (36) The eye condition is associated with retinitis pigmentosa 38, and the therapeutic product is a MER protein. a tocogene, tyrosine kinase (MERTK); (37) The eye condition is associated with retinitis pigmentosa 40 and the therapeutic product is a phosphodiesterase inhibitor. protease 6B (PDE6B); (38) The eye condition is associated with retinitis pigmentosa 41 and the therapeutic product is prominence 1(PROM1); (39) The eye condition is associated with retinitis pigmentosa 56, and the therapeutic product is an interphotoreceptor matrix proteoglycan 2 (IMPG2); (40) The eye condition is associated with retinitis pigmentosa 62 and the therapeutic product is administered to male germ cells. is a cytoplasmic associ- ated kinase (MAK); (41) The eye condition is associated with retinitis pigmentosa 80, and the therapeutic product is delivered via intraflagellar transport. 140 (IFT140); or (42) The eye condition is associated with Best's disease, and the therapeutic product is bestrophin 1 (B EST1). 31. (1) The eye condition is associated with X-linked retinitis pigmentosa (XLRP), and the therapeutic The product is retinitis pigmentosa GTPase regulator (RPGR); (2) the eye condition is associated with color vision deficiency, and the therapeutic product is a cyclic nucleotide gate Channel beta 3 (CNGB3); or (3) The eye condition is associated with color vision deficiency, and the therapeutic product is a cyclic nucleotide gate. Any one of paragraphs 1 to 11 and 15 to 18, which is Channel Alpha 3 (CNGA3) The method described below. 32. The recombinant viral vector comprises a promoter or an enhancer-promoter and further comprising a nucleotide sequence encoding said promoter or enhancer-protein. The nucleotide sequence encoding the promoter is a promoter or enhancer-promoter operably linked to a nucleotide sequence, (1) CAG promoter; (2) CBA promoter; (3) CMV promoter; (4) PR1.7 promoter; (5) rhodopsin kinase (GRK1) photoreceptor-specific enhancer-promoter; (6) hCARp promoter; (7)hRKp; (8) cone photoreceptor-specific human arrestin 3 (ARR3) promoter; (9) rhodopsin promoter; or (10) The method according to any one of paragraphs 1 to 31, wherein the promoter is a U6 promoter. 33. The recombinant viral vector comprises a nucleotide sequence encoding a cone-specific promoter. and the nucleotide sequence encoding the cone-specific promoter is operably linked to said nucleotide sequence encoding the therapeutic product, (1) The eye condition is associated with red-green color blindness, and the therapeutic product is a compound that inhibits L opsin (OPN1L W); (2) the eye condition is associated with red-green color blindness, and the therapeutic product is a compound that inhibits M opsin (OPN1M W); (3) The ocular condition is associated with blue-cone monochromatism, and the therapeutic product is a phosphodiesterase (MOP)-dependent ... PN1MW); (4) The eye condition is associated with cone dystrophy and the therapeutic product is a guanylate synthase. is a glucose-activating factor 1A (GUCA1A); or (5) The eye condition is associated with blue-cone monochromatism (BCM), and the therapeutic product is The method according to any one of paragraphs 1 to 11 and 13 to 15, wherein the antibody is pSin (OPN1LW). Law. 34. The administering step delivers a therapeutically effective amount of the therapeutic product to the retina of the human subject. , The method according to any one of paragraphs 1 to 33. 35. The therapeutically effective amount of the therapeutic product is produced by human retinal cells of the human subject. 35. The method of paragraph 34, wherein 36. The therapeutically effective amount of the therapeutic product is administered to the human subject in the form of human photoreceptor cells, horizontal cells, or the like. , bipolar cells, amacrine cells, retinal ganglion cells, and / or retinal pigment epithelial cells of the outer limiting membrane 35. The method of paragraph 34, wherein the antibody is produced by a cell. 37. The method of paragraph 36, wherein the human photoreceptor cells are cone cells and / or rod cells. How to do it. 38. The retinal ganglion cells are midget cells, parasol cells, bilayered cells, giant retinal ganglion cells. 37. The method of paragraph 36, wherein the cells are ganglion cells, photosensitive ganglion cells, and / or Müller glia. . 39. Any of paragraphs 1 to 38, wherein the recombinant viral vector is an rAAV vector. 1. The method according to claim 1. 40. The method of paragraph 39, wherein the recombinant viral vector is an rAAV8 vector. Law. 41. After the administration step, an infrared thermal camera is used to monitor the post-ocular injection of the substance injected into the eye. 41. The method of claim 1, further comprising monitoring the thermal profile of How to do it. 42. The method described in paragraph 41, wherein the infrared thermal camera is a FLIR T530 infrared thermal camera. How to post. 43. The recombinant nucleotide expression vector is about 6.0 x 10 10 Genome copies / eye 44. The method of any one of paragraphs 1 to 43, wherein the dose is administered in a single dose. 44. The recombinant nucleotide expression vector is about 1.6 x 10 11 Genome copies / eye 44. The method of any one of paragraphs 1 to 43, wherein the dose is administered in a single dose. 45. The recombinant nucleotide expression vector is about 2.5 x 10 11 Genome copies / eye 44. The method of any one of paragraphs 1 to 43, wherein the dose is administered in a single dose. 46. ​​The recombinant nucleotide expression vector is about 5.0 x 10 11 Genome copies / eye 44. The method of any one of paragraphs 1 to 43, wherein the dose is administered in a single dose. 47. The recombinant nucleotide expression vector is about 3.0 x 10 12 Genome copies / eye 44. The method of any one of paragraphs 1 to 43, wherein the dose is administered in a single dose. [Brief explanation of the drawings]

[0066] 5. Brief description of the drawings [Figure 1] 1 shows a suprachoroidal drug delivery device manufactured by Clearside® Biomedical, Inc.

[0067] [Figure 2] 1 shows a subretinal drug delivery device manufactured by Janssen Pharmaceuticals, Inc., which includes a catheter that can be inserted into the suprachoroidal space and passed through the suprachoroidal space toward the posterior pole, where a fine needle is used to inject into the subretinal space.

[0068] [Figure 3] 1 shows a cross section of the human eye.

[0069] [Figure 4] A-D show illustrative diagrams of the posterior juxtascleral depot procedure.

[0070] [Figure 5] A schematic diagram of the AAV8-anti-VEGF Fab genome is shown.

[0071] [Figure 6] 1 shows the use of an infrared thermal camera to monitor the thermal profile after suprachoroidal injection.

[0072] [Figure 7] A and B show a microvolume injector drug delivery device manufactured by Altaviz.

[0073] [Figure 8] This figure shows a drug delivery device manufactured by Visionisti OY. Specifically, Figure 8A illustrates an injection adapter that can convert a short 30g hypodermic needle into a suprachoroidal / subretinal needle. The device allows control of the length of the needle tip exposed at the distal end of the adapter. Adjustments can be made in 10 μL increments. The device has the ability to be adjusted for suprachoroidal and / or extraocular subretinal delivery. Figure 8B illustrates a needle adapter guide that holds the lid open and holds the needle at the optimal angle and depth for delivery. The needle adapter is secured to a stable device. The needle adapter is a standardized and optimized all-in-one tool for in-office suprachoroidal and / or subretinal injections. DETAILED DESCRIPTION OF THE INVENTION

[0074] 6. MODE FOR CARRYING OUT THE INVENTION For example, recombinant viral vectors such as recombinant adeno-associated viral (rAAV) vectors into the retina / vitreous humor of the eye of a human subject to treat an ocular condition, including For example, therapeutic proteins (e.g., antibodies), therapeutic RNAs (e.g., shRNA, siR The present invention provides compositions and methods for the delivery of therapeutic aptamers (e.g., therapeutic RNAs, miRNAs, and miRNAs). Provided in the details.

[0075] Therapeutic products include, for example, therapeutic proteins (e.g., antibodies), therapeutic RNAs (e.g., shRNA, siRNA, and miRNA), or therapeutic aptamers. do.

[0076] In certain embodiments, the therapeutic product is a human protein or an antibody against a human protein. Antibodies include monoclonal antibodies, polyclonal antibodies, recombinantly produced antibodies, and human antibodies. Antibodies, humanized antibodies, chimeric antibodies, synthetic antibodies, tetramers containing two heavy chain molecules and two light chain molecules Monomeric antibody, antibody light chain monomer, antibody heavy chain monomer, antibody light chain dimer, antibody heavy chain dimer , antibody light chain-heavy chain pair, intrabody, heteroconjugate antibody, monovalent antibody, full-length antibody and antigen-binding fragments of the above, as well as fusion proteins thereof. Such antigen-binding fragments include single domain antibodies (heavy chain antibodies (VHH) or or nanobody variable domains), Fab, F(ab')2, and scFv (single chain variable Fvs) In certain embodiments, therapeutic products include, but are not limited to, In certain embodiments, the product (e.g., a therapeutic protein) is post-translationally modified. The decoration is intended to provide a therapeutic product (e.g., a therapeutic protein) using a particular pathway as described herein. Therapeutic products (e.g., post-translationally modified therapeutic products) are specific to the cell type to which they are delivered. Delivery is via gene therapy to create a permanent depot that provides a continuous supply of For example, recombinant viral vectors or recombinant DNA expression vectors encoding therapeutic products. The constructs (collectively, "recombinant vectors") are injected into the choroid of the eye(s) of a human patient. superior space, subretinal space (with or without vitrectomy (e.g., catheter through the suprachoroidal space or via perichoroidal injection), the intraretinal space, the vitreous cavity, and / or the retinal space. This can be achieved by administration to the outer surface of the membrane (ie, juxtascleral administration).

[0077] 6.1 Methods for Delivery of Therapeutic Products In one aspect, a method of subretinal administration without vitrectomy for treating an ocular condition is disclosed herein. The method provides for administering a therapeutic product to the subretinal space of the eye of a human subject in need of treatment. A recombinant viral vector containing a nucleotide sequence encoding the therapeutic product is administered to express the therapeutic product. and subjecting the eye of the human patient to a vitrectomy to provide treatment for the ocular condition. In certain embodiments, the administering step does not include administering to the retina of the eye of said human subject. and administering a recombinant viral vector therapeutic product to the subchoroidal space via the suprachoroidal space of the human subject's eye. In certain embodiments, the administering step includes administering a drug to a patient. A catheter that can be passed through the epiretinal space toward the posterior pole and injects a fine needle into the subretinal space at the posterior pole. In certain embodiments, administration is by use of a subretinal drug delivery device comprising: The steps include inserting a catheter of a subretinal drug delivery device into the suprachoroidal space and This includes passing through a cavity.

[0078] In another aspect, provided herein is a method for treating an ocular condition, the method comprising: a nucleotide sequence encoding a therapeutic product into the subretinal space of the eye of a human subject in need thereof. Administering a recombinant viral vector to express a therapeutic product and provide treatment for an ocular condition and wherein the method does not include performing a vitrectomy on the eye of the human patient. In some embodiments, the administering step comprises administering a retinal or retinal composition to the subretinal space of the eye of the human subject, or to the choroid of the eye of the human subject. This involves administering a recombinant viral vector therapeutic product via the epithelial space. In some embodiments, the administration step involves inserting the catheter into the suprachoroidal space and passing it through the suprachoroidal space toward the posterior pole. and a catheter for injecting a fine needle into the subretinal space at the posterior pole. In certain embodiments, the administering step is by use of a subretinal drug delivery device. The method includes inserting a catheter into the suprachoroidal space and passing the catheter through the suprachoroidal space.

[0079] In one aspect, a method of subretinal administration in conjunction with vitrectomy to treat an ocular condition is described herein. The method includes delivering a therapeutic product to the subretinal space of the eye of a human subject in need of treatment. A recombinant viral vector containing a nucleotide sequence for expression of a therapeutic product is administered. and providing treatment for an ocular condition, the method comprising performing a vitrectomy on the eye of the human patient. In certain embodiments, the vitrectomy is a partial vitrectomy.

[0080] In another aspect, provided herein is a method for treating an ocular condition, the method comprising: a nucleotide sequence encoding a therapeutic product into the subretinal space of the eye of a human subject in need thereof. Administering a recombinant viral vector to express a therapeutic product and provide treatment for an ocular condition and the method includes performing a vitrectomy on the eye of the human patient. In an embodiment, the vitrectomy is a partial vitrectomy.

[0081] In one aspect, provided herein is a method of suprachoroidal administration for treating an ocular condition, the method comprising: The method comprises delivering a nucleoside encoding a therapeutic product into the suprachoroidal space of the eye of a human subject in need of treatment. and administering a recombinant viral vector containing the nucleotide sequence to express a therapeutic product to treat the ocular condition. In certain embodiments, the administering step comprises administering a recombinant viral vector to the host. by injecting the agent into the suprachoroidal space using a suprachoroidal drug delivery device. In certain embodiments, the suprachoroidal drug delivery device is a microinjector. is.

[0082] In another aspect, provided herein is a method for treating an ocular condition, the method comprising: a nucleotide sequence encoding a therapeutic product in the suprachoroidal space of the eye of a human subject in need thereof; and administering a recombinant viral vector containing the compound to express a therapeutic product to provide treatment for the ocular condition. In certain embodiments, the administering step comprises administering the recombinant viral vector to a mammalian cell in a mammalian cell line. by injection into the suprachoroidal space using a suprachoroidal drug delivery device. In certain embodiments, the suprachoroidal drug delivery device is a microinjector.

[0083] In certain embodiments, delivery to the subretinal or suprachoroidal space is achieved by methods described in International Publication No. WO20 16 / 042162, WO2017 / 046358, WO2017 / 158365, and WO2017 / 158366 (each of which is incorporated herein by reference in its entirety). This can be done using the methods and / or devices described and disclosed in

[0084] In one aspect, provided herein is a method of administration to the extrascleral space to treat an ocular condition. The method includes delivering a therapeutic product to the outer surface of the sclera of the eye of a human subject in need of treatment. A recombinant viral vector containing a nucleotide sequence for expression of a therapeutic product is administered. In certain embodiments, the administering step includes administering a cannula The tip of the cannula can be inserted into the scleral surface and placed directly in apposition to the scleral surface. In certain embodiments, the administration step involves the use of a juxtascleral drug delivery device. The procedure involves inserting the tip of the cannula into the scleral surface and placing it directly in apposition to the scleral surface. include.

[0085] In another aspect, provided herein is a method for treating an ocular condition, the method comprising: a nucleotide sequence encoding a therapeutic product on the outer surface of the sclera of the eye of a human subject in need thereof; and administering a recombinant viral vector containing the compound to express a therapeutic product to treat an ocular condition. In certain embodiments, the administering step includes applying the tip of the cannula to the scleral surface. a juxtascleral drug delivery device that includes a cannula that can be inserted into the sclera and placed directly in apposition to the scleral surface; In certain embodiments, the administering step is by use of a device. This includes inserting the end into the scleral surface and directly apposing it to the scleral surface.

[0086] In one aspect, provided herein is a method of intravitreal administration for treating an ocular condition, the method comprising: The method comprises administering a nucleotide sequence encoding a therapeutic product into the vitreous cavity of the eye of a human subject in need of treatment. A recombinant viral vector containing the gene sequence is administered to express a therapeutic product to treat the ocular condition. In certain embodiments, the administering step includes administering a recombinant viral vector. by injecting the drug 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, the method comprising: and administering to a human subject in need thereof a nucleotide sequence encoding a therapeutic product into the vitreous cavity of the eye of the subject. and administering a recombinant viral vector containing the compound to express a therapeutic product to treat the ocular condition. In certain embodiments, the administering step comprises administering the recombinant viral vector to a mammalian cell. By injection into the vitreous cavity using an intravitreal drug delivery device. In certain embodiments, the intravitreal drug delivery device is a microinjector.

[0087] In certain embodiments, the therapeutic product is an anti-human vascular endothelial growth factor (hVEGF) antibody. isn't it.

[0088] In certain embodiments, the ocular condition is neovascular age-related macular degeneration (nAMD) ("weeping macular degeneration"). Also known as "exudative" and neovascular AMD ("WAMD" or "wet AMD") (not related to the

[0089] In certain embodiments, the therapeutic product is an anti-hVEGF antibody.

[0090] In certain embodiments, the ocular condition is associated with nAMD.

[0091] In certain embodiments, the ocular condition is associated with nAMD and the therapeutic product is an anti-hVEGF antibody. It is the body.

[0092] In one aspect, a method of subretinal administration in conjunction with vitrectomy to treat an ocular condition is described herein. The method includes delivering a therapeutic product to the subretinal space of the eye of a human subject in need of treatment. A recombinant viral vector containing a nucleotide sequence for expression of a therapeutic product is administered. and providing treatment for an ocular condition, the method comprising performing a vitrectomy on the eye of the human patient. 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.

[0093] In another aspect, provided herein is a method for treating an ocular condition, the method comprising: a nucleotide sequence encoding a therapeutic product into the subretinal space of the eye of a human subject in need thereof. Administering a recombinant viral vector to express a therapeutic product and provide treatment for an ocular condition the method includes performing a vitrectomy on the eye of the human patient, and the therapeutic product is In certain embodiments, the antibody is an anti-human vascular endothelial growth factor (hVEGF) antibody. The condition is an ocular disease or a disease involving multiple organs including the eye. The vitrectomy is a partial vitrectomy.

[0094] In one aspect, provided herein is a method of subretinal administration for treating an ocular condition, the method comprising: The method comprises administering to a human subject in need of treatment a laser beam to the optic disc, fovea, and macula located in the posterior segment of the eye. A recombinant viral vector containing a nucleotide sequence encoding a therapeutic product is delivered to the subretinal space. and administering to the subject a therapeutic product to effect treatment of the ocular condition, the method comprising: In certain embodiments, the injection step does not include performing a vitrectomy on the eye of the human patient. is by intravitreal injection. In certain embodiments, the method of intravitreal administration comprises: Provide uniform expression of the therapeutic product throughout the eye (e.g., expression levels at the injection site) The variation in expression levels was 5%, 10%, 20%, 30%, and 40% compared to expression levels in other regions of the eye. %, or less than 50%). In certain embodiments, the transvitreal injection is performed on the superior or inferior side of the eye. The needle is inserted into the sclera through the inferior side of the eye, and the needle is passed completely through the vitreous body to inject the recombinant virus. In certain embodiments, the needle includes: In certain embodiments, the intravitreal injection is performed using a cannula. A needle is inserted into the sclera, a cannula is inserted into the trocar, and the recombinant virus is injected through the vitreous body. In certain embodiments, the therapeutic vector is injected into the subretinal space on the opposite side. In certain embodiments, the anti-hVEGF antibody is an anti-hVEGF antibody. In certain embodiments, the anti-hVEGF antigen-binding fragment is an EGF antigen-binding fragment. The fragments are Fab, F(ab')2, or single-chain variable fragments (scFv). In certain embodiments, the anti-hVEGF antibody is selected from the group consisting of the antibody of SEQ ID NO: 2 or SEQ ID NO: 4. a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 3, and a light chain comprising the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 3. In certain embodiments, the anti-hVEGF antibody comprises the light chain CDRs of SEQ ID NOs: 14-16. 1 to 3 and heavy chain CDR1 of SEQ ID NOs: 17 to 19 or SEQ ID NOs: 20, 18, and 21 In certain embodiments, the ocular condition is nAMD, dry age-related macular degeneration. (dry AMD), retinal vein occlusion (RVO), diabetic macular edema (DME), or diabetes In certain embodiments, the ocular condition is associated with diabetic retinopathy (DR). To connect.

[0095] In another aspect, provided herein is a method for treating an ocular condition, the method comprising: In the subretinal space around the optic disc, fovea, and macula located in the posterior segment of the eye of a human subject in need thereof. administering a recombinant viral vector containing a nucleotide sequence encoding a therapeutic product, and expressing a therapeutic product to provide treatment for the ocular condition, the method comprising administering to the human patient In certain embodiments, the injection step does not include performing a vitrectomy on the eye. In certain embodiments, the method of intravitreal administration is by intraocular injection. This results in uniform expression of the therapeutic product (e.g., variations in expression levels at the injection site, 5%, 10%, 20%, 30%, 40%, or In certain embodiments, the transvitreal injection is performed on the superior or inferior side of the eye. A sharp needle is inserted into the sclera through the vitreous body, and the sharp needle is passed completely through the vitreous body to deliver the recombinant viral vector. into the contralateral subretinal space. In certain embodiments, the needle is at 2 o'clock or In certain embodiments, the transvitreal injection is performed by inserting the trocar into the sclera. The cannula is inserted into the vitreous body, and the recombinant viral vector is delivered through the vitreous body. In certain embodiments, the therapeutic product comprises an anti-histamine. In certain embodiments, the anti-hVEGF antibody is an anti-hVEGF antibody. In certain embodiments, the anti-hVEGF antigen-binding fragment is an anti-hVEGF antigen-binding fragment. The fragment may be a Fab, F(ab')2, or a single chain variable fragment (scFv). In certain embodiments, the anti-hVEGF antibody has 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, the anti-hVEGF antibody comprises light chain CDRs 1-3 of SEQ ID NOs: 14-16. and heavy chain CDRs 1 to 3 of SEQ ID NOs: 17 to 19 or SEQ ID NOs: 20, 18, and 21. In certain embodiments, the ocular condition is nAMD, dry age-related macular degeneration (nAMD). MD), retinal vein occlusion (RVO), diabetic macular edema (DME), or diabetic retinal In certain embodiments, the ocular condition is associated with nAMD.

[0096] In certain embodiments of the methods described herein, the administering step comprises administering a therapeutically effective amount of a therapeutic product. The substance is delivered to the retina of the human subject.

[0097] In certain embodiments of the methods described herein, a therapeutically effective amount of a therapeutic product is administered to said human It is produced by human retinal cells in the target subject.

[0098] In certain embodiments of the methods described herein, a therapeutically effective amount of a therapeutic product is administered to said human Human photoreceptor cells, horizontal cells, bipolar cells, amacrine cells, retinal ganglion cells, and It is produced by the retinal pigment epithelial cells of the outer limiting membrane and / or the retinal pigment epithelium.

[0099] In certain embodiments of the methods described herein, the human photoreceptor cells are cone cells and and / or rod cells.

[0100] In certain embodiments of the methods described herein, the retinal ganglion cells are midget cells, Parasol cells, bistratified cells, giant retinal ganglion cells, photosensitive ganglion cells, and / or murine retinal ganglion cells It's Laglia.

[0101] In certain embodiments of the methods described herein, the recombinant viral vector is V vector (e.g., rAAV8, rAAV2, rAAV2tYF, or rAAV5 vector) (Kuta).

[0102] In certain embodiments of the methods described herein, the recombinant viral vector is It is a V8 vector.

[0103] In certain embodiments of the methods described herein, delivery to the eye includes delivery to the retina, choroid, and / or delivery to the vitreous humor.

[0104] 6.1.1 Post-translational modifications In certain embodiments, a therapeutic product (e.g., a therapeutic protein) is post-translationally modified. In certain embodiments, post-translational modifications are performed to modify the structure of a therapeutic product (e.g., a therapeutic protein). It is specific to the cell type that is delivered using the particular route described herein.

[0105] In certain embodiments, 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 ADP-ribosylation. In certain embodiments, 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 centrination. In another particular embodiment, the post-translational modification is a ubiquitination-like protein modification.

[0106] In certain embodiments, the therapeutic product is a recombinant vector in human immortalized retina-derived cells. It is post-translationally modified upon expression from the

[0107] In certain embodiments, administration of the recombinant vector results in the release of a therapeutic product containing post-translational modifications. This results in the formation of a depot that releases

[0108] In certain embodiments, the recombinant vector is used to transduce retina-derived cells in culture. When used for this purpose, it results in the production of therapeutic products that contain post-translational modifications.

[0109] Post-translational modifications can be detected by any method known in the art for detecting post-translational modifications, e.g. , detected by Western blot, chromatography, or flow cytometry It is possible.

[0110] In certain embodiments, post-translational modification is achieved by cytosolic modification using radioactive substrates or substrate precursor molecules. This can be detected by in vivo labeling of the protein pool, which can be used to target the therapeutic product. Phosphate, fatty acyl (e.g., myristoyl, or palmityl), centrin, methyl , acetyl, hydroxyl, iodine, flavin, ubiquitin, or ADP-ribosyl The analysis of modified proteins involves the incorporation of radiolabeled moieties, including but not limited to: This is typically done by electrophoresis and autoradiography, with the eye prior to electrophoresis Immunoprecipitation of the target protein increases specificity.

[0111] In certain embodiments, post-translationally, labeling moieties (radioactive compounds) can be added to therapeutic products in vitro. detection by enzymatic incorporation of a label (including but not limited to a chromophore, luminescent, or fluorescent label) This allows us to estimate the state of modification in vivo.

[0112] In certain embodiments, post-translationally, the modified therapeutic product is Alterations in the electrophoretic mobility of therapeutic products (e.g., glycosylation or ubiquitination) It can be detected by analysis.

[0113] In certain embodiments, post-translationally, a thin layer of radiolabeled fatty acids extracted from the therapeutic product is prepared. It can be detected by chromatography.

[0114] In certain embodiments, post-translation, a surfactant-rich layer or surfactant layer is formed by phase separation. and between aqueous and surfactant-rich environments. It can be detected by the effect of enzymatic treatment of the therapeutic product.

[0115] In certain embodiments, post-translational analysis can be performed using, for example, Western blot or flow cytometry. Modified forms of the protein can be detected by antibody recognition by the ELISA.

[0116] 6.1.2 Constructs and Formulations Recombinant viruses encoding therapeutic products for use in the methods provided herein. vector or other recombinant DNA expression construct (collectively, "recombinant vectors") The recombinant viral vectors and other DNA expression constructs provided herein are The target may be a therapeutic product (e.g., a therapeutic protein (e.g., an antibody), a therapeutic RNA (e.g., , shRNA, siRNA, and miRNA), and therapeutic aptamers)) target cells ( The delivery of therapeutic products to the retinal pigment epithelium (e.g., retinal pigment epithelial cells) is also suitable. Delivery means include recombinant viral vectors, liposomes, other lipid-containing complexes, other polymer complexes, etc. coalescence, synthetic modified mRNA, unmodified mRNA, small molecules, non-biologically active molecules (e.g. gold particles) molecules), polymeric molecules (e.g., dendrimers), naked DNA, plasmids, phages, In some embodiments, the vector may be a transposon, a cosmid, or an episome. is a targeted vector, for example, a vector that targets retinal pigment epithelial cells.

[0117] In some aspects, the disclosure provides a nucleic acid for use, the nucleic acid being a nucleic acid comprising a nucleic acid sequence as described herein. promoter or enhancer-encoding a therapeutic product operably linked to a promoter Do it.

[0118] In certain embodiments, the nucleic acid sequence comprises one or more nucleic acids (e.g., polynucleotides). Recombinant vectors are provided herein. The nucleic acid may be DNA, RNA, or both DNA and RNA. In certain embodiments, the DNA may comprise a promoter sequence, a target sequence, a target gene, a target protein ... a sequence encoding a therapeutic product of interest, an untranslated region, and a termination sequence. In certain embodiments, the recombinant vectors provided herein include one or more of the sequences. The vector contains a promoter operably linked to a sequence encoding a therapeutic product of interest. include.

[0119] In certain embodiments, the nucleic acids (e.g., polynucleotides) disclosed herein and Nucleic acid sequences can be optimized using, for example, any codon optimization technique known to those skilled in the art (e.g., Quax See the review by et al., 2015, Mol Cell 59:149-161. The codons can be optimized via

[0120] (a) mRNA In certain embodiments, the recombinant vectors provided herein can be used to express a therapeutic product of interest. The modified mRNA encodes a therapeutic product that delivers the therapeutic product to cells of the eye, such as retinal pigment epithelial cells. The synthesis of modified and unmodified mRNA to achieve this is described, for example, in Hansson et al. , J.Biol.Chem., 2015, 290(9):5661-5672 (reference (which is incorporated herein in its entirety). In certain embodiments, the treatment Modified mRNAs encoding the desired product moieties are provided herein.

[0121] (b) shRNA, siRNA, and miRNA In certain embodiments, the recombinant vectors provided herein can be used to encode shRNA, siR The therapeutic product comprises a nucleotide sequence that encodes a therapeutic product that is a nucleotide sequence encoding ...

[0122] (c) Recombinant viral vector Recombinant viral vectors include recombinant adenoviruses, adeno-associated viruses (AAVs, For example, AAV1, AAV2, AAV2tYF, AAV3, AAV4, AAV5, AAV 6, AAV7, AAV8, AAV9, AAV10, AAV11, and AAVrh10). Lentivirus, helper-dependent adenovirus, herpes simplex virus, poxvirus Rus, Sendai virus (hemagglutinin virus of Japan (HVJ), alphavirus, vaccinia virus, and retrovirus vectors Retroviral vectors include murine leukemia viruses (MLV) and human immunodeficiency virus (HIV). Alphavirus vectors include vectors based on human immunodeficiency virus (HIV). These include Semliki Forest virus (SFV) and Sindbis virus (SIN). In certain embodiments, the recombinant viral vectors provided herein are intended to be useful in the treatment of psoriasis, as they are useful in humans. In certain embodiments, the recombinant viral vector is modified to be replication-deficient. A placed in a hybrid vector, e.g., a "neutral" adenovirus vector In certain embodiments, the viral capsid from the first virus is an AV vector. a recombinant viral vector comprising a viral envelope protein from the first virus and a viral envelope protein from a second virus; In certain embodiments, the second virus is a vesicular stomatitis virus. In a more particular embodiment, the envelope protein is VSV- It is a G protein.

[0123] In certain embodiments, the recombinant viral vectors provided herein are HIV-based In certain embodiments, the HIV-based viral vectors provided herein are The vector contains at least two polynucleotides, the gag and pol genes IV genome, and the env gene is from another virus.

[0124] In certain embodiments, the recombinant viral vectors provided herein are directed against herpes simplex viruses. In certain embodiments, the viral vectors provided herein are based on viral vectors. Herpes simplex virus-based vectors that deliver HIV-1-associated ... ) gene and are therefore modified to be non-cytotoxic.

[0125] In certain embodiments, the recombinant viral vectors provided herein are MLV-based. In certain embodiments, the MLV-based viral vectors provided herein are The vectors contain up to 8 kb of heterologous DNA in place of the viral genes.

[0126] In certain embodiments, the recombinant viral vectors provided herein are lentiviral vectors. In certain embodiments, the vectors provided herein are based on the Antiviral vectors are derived from human lentiviruses. In certain embodiments, the present invention The lentiviral vectors provided herein are derived from non-human lentiviruses. In certain embodiments, the lentiviral vectors provided herein are In certain embodiments, the lentil viras provided herein are packaged in a capsule. The vector contains the following elements: long terminal repeats, primer binding sites, polyprints. It comprises one or more of a lacto, an att site, and an encapsidation site.

[0127] In certain embodiments, the recombinant viral vectors provided herein are alphaviral vectors. In certain embodiments, the vectors provided herein are virus-based viral vectors. Alphavirus vectors are recombinant, replication-defective alphaviruses. In embodiments, the alphavirus replica in the alphavirus vectors provided herein Consequences of this are the ability to bind specific virions by displaying functional heterologous ligands on their virion surface. Targeted to cell types.

[0128] In certain embodiments, the recombinant viral vectors provided herein are AAV-based In a preferred embodiment, the recombinant viruses provided herein are In certain embodiments, the vector is an AAV8-based viral vector. The AAV8-based viral vectors provided herein retain tropism for retinal cells. In certain embodiments, the AAV-based vectors provided herein are AAV The rep gene (required for replication) and / or the AAV cap gene (capsid The AAV serotypes encode the ATPase inhibitor (ATP1A) required for the synthesis of ATP-dependent proteins. Several AAV serotypes have been identified. In certain embodiments, the AAV-based vectors provided herein are one of the AAV or comprises components from multiple serotypes. In certain embodiments, the A provided herein AV-based vectors include AAV1, AAV2, AAV2tYF, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10, AAV11, or AAVrhlO and AAVrhlO capsid components. The AAV-based vectors provided herein include AAV8, AAV9, AAV10, , AAV11, or AAVrh10 serotypes.

[0129] In a specific embodiment, the therapeutic Viral genome containing cassettes for expression of AAV8 products and AAV8 capsid proteins or the amino acid sequence of the AAV8 capsid protein (SEQ ID NO: 48) At least 95%, 96%, 97%, 98%, 99%, or 99.9% identical to the sequence It contains a viral capsid that retains the biological function of the AAV8 capsid while AAV8 vectors are provided. In certain embodiments, the encoded AAV8 capsid is The numbers are 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 1 6, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or the sequence of SEQ ID NO: 48 with 30 amino acid substitutions, It retains its physical function.

[0130] In certain embodiments, the AAV used in the methods described herein is Anc 80 or Anc80L65, which are Zinn et al., 2015, Ce ll Rep.12(6):1056-1068 (incorporated by reference in its entirety) In certain embodiments, the method described herein is as described in The AAV used contains the following amino acid insertions: LGETTRP or LALGETTRP. 9,193,956; 9,458,517; and No. 9,587,282 and U.S. Patent Application Publication No. 2016 / 0376323 (and (each of which is incorporated herein by reference in its entirety). In certain embodiments, the AAV used in the methods described herein is AAV.7m 8, which is disclosed in U.S. Patent Nos. 9,193,956; 9,458,517; and No. 9,587,282 and U.S. Patent Application Publication No. 2016 / 0376323 (the (each of which is incorporated herein by reference in its entirety). In certain embodiments, the AAV used in the methods described herein is described in U.S. Pat. The AAV may be any of the AAVs disclosed in US Pat. No. 5,855,971, such as AAV-PHP.B. In certain embodiments, the AAVs used in the methods described herein are each The following patents and patent applications are incorporated herein by reference in their entireties: U.S. Pat. No. 7,529,233; ,906,111; Same No. 8,524,446; Same No. 8,999,678; Same No. 8, No. 628,966; No. 8,927,514; No. 8,734,809; No. 9,2 No. 84,357; No. 9,409,953; No. 9,169,299; No. 9,19 Nos. 3,956; 9,458,517; and 9,587,282, U.S. Pat. Appl. Publication number 2015 / 0374803;2015 / 0126588;2017 / 006790 8;2013 / 0224836;2016 / 0215024;2017 / 0051257 ; and International Patent Application Nos. PCT / US2015 / 034799; PCT / EP201 5 / 053335.

[0131] AAV8-based viral vectors are used in certain embodiments of the methods described herein. The nucleic acid sequences of AAV-based viral vectors, as well as recombinant AAV and A Methods for producing AV capsids are described, for example, in U.S. Pat. No. 7,282,199 B2; U.S. Pat. Patent No. 7,790,449 B2, U.S. Patent No. 8,318,480 B2, U.S. Patent No. No. 8,962,332 B2 and International Application No. PCT / EP2014 / 076466 (and (each of which is incorporated herein by reference in its entirety). AAV (e.g., AAV8)-based viral vectors encoding therapeutic products are described herein. Provided in writing.

[0132] In certain embodiments, single-stranded AAV (ssAAV) may be used. In certain embodiments, self-complementary vectors, such as scAAV, may be used (e.g., Wu,2007,Human Gene Therapy,18(2):171-82, McCarty et al,2001,Gene Therapy,Vol 8,Nu Amber 16, Pages 1248-1254; and U.S. Patent No. 6,596,5 Nos. 35; 7,125,717; and 7,456,683 (each of which is incorporated by reference). (see, e.g., U.S. Pat. No. 6,223,629, which is incorporated herein in its entirety).

[0133] In certain embodiments, the recombinant viral vectors used in the methods described herein The vector is a recombinant adenovirus vector. The recombinant adenovirus contains an E1 deletion. with or without E3 deletion, and with an expression cassette inserted into either deleted region. The recombinant adenovirus may be a first generation vector in which the E2 and E4 regions are inserted. The vector may be a second generation vector containing a complete or partial deletion of the helper region. -dependent adenoviruses contain the adenovirus inverted terminal repeats and packaging signal The therapeutic product contains only the phi sequence between the packaging signal and the 3'ITR. A stuffer sequence was inserted to maintain the genome at approximately the wild-type size of 36 kb. Exemplary Protocol for Producing Adenoviral Vectors with or without Arrays Alba et al., 2005, “Gutless adenovirus: ast generation adenovirus for gene thera py,” Gene Therapy 12:S18-S27 (incorporated by reference in its entirety) (incorporated herein).

[0134] In certain embodiments, the recombinant viral vectors used in the methods described herein The vector is a lentivirus-based viral vector. It uses four plasmids. Constructs are created using: Gag / pol sequence-containing plasmid, Rev sequence-containing plasmid The plasmids, envelope protein-containing plasmids (i.e., VSV-G), and Cis plasmid with packaging element and therapeutic product-containing plasmid.

[0135] For lentiviral vector production, the four plasmids were transfected into cells (i.e., HEK 293 line cells), in which case, in particular, polyethyleneimine or Calcium phosphate can be used as a transfection agent. The virus is collected in the supernatant (lentiviruses bud from the cells to become active). (Cell harvesting is not / should not be necessary because the supernatant needs to be filtered (0.45 μL) m) and then magnesium chloride and benzonase are added. Further downstream processes can vary widely, and the use of TFF and column chromatography Other processes involve column chromatography. With or without ultracentrifugation, an exemplary method for the production of lentiviral vectors is used. The protocol is described in Lesch et al., 2011, “Production and d purification of lentiviral vector gene rated in 293T suspension cells with bacu loviral vectors,”Gene Therapy 18:531-538 , and Ausubel et al., 2012, “Production of CG MP-Grade Lentiviral Vectors,”Bioprocess Int. 10(2):32-43 (both of which are incorporated herein by reference in their entireties). can be found in

[0136] (d) Promoters and modifiers of gene expression: In certain embodiments, the recombinant vectors provided herein are useful for the delivery of therapeutic products or or components that regulate expression (e.g., "expression control elements"). In embodiments, the recombinant vectors provided herein contain components that regulate the expression of a therapeutic product. In certain embodiments, the recombinant vectors provided herein are capable of being inserted into cells. In certain embodiments, the compounds provided herein include components that affect binding or targeting. The recombinant vectors provided contain polynucleotides that encode therapeutic products within cells after uptake. In certain embodiments, the compounds provided herein include components that affect the localization of the target molecule. The recombinant vector can be used to express, for example, a cell line incorporating a polynucleotide encoding a therapeutic product. can be used as a detectable or selectable marker to detect or select cells. It includes components that can

[0137] In certain embodiments, the recombinant vectors provided herein contain one or more promoters. In certain embodiments, the promoter is a constitutive promoter. In certain embodiments, the promoter is an inducible promoter. Inducible so that expression of the therapeutic product can be switched on and off as desired. Promoters may be preferred. Such promoters include, for example, hypoxia-inducible promoters. Motor and drug-inducible promoters, e.g., induced by rapamycin and related agents. Hypoxia-inducible promoters include promoters that contain HIF binding sites. For example, Schodel, et al., 2011, Blo od 117(23):e207-e217 and Kenneth and Rocha, 2008, Biochem J. 414:19-29 (respectively, hypoxia induction by reference (which is incorporated herein by reference for its teachings on promoters). Hypoxia-inducible promoters that can be used in the present invention include the erythropoietin promoter and and N-WASP promoter (for disclosure of erythropoietin promoters) Tsuchiya, 1993, J. Biochem. 113:395, N-WAS For disclosure of the P promoter, see Salvi, 2017, Biochemistry and Biophysics Reports 9:13-21 (both by reference (see incorporated herein for teachings on hypoxia-inducible promoters). The recombinant vector may contain a drug-inducible promoter, such as a promoter for rapamycin and related analogs. The promoter may contain a promoter that is inducible by administration (see, for example, International Patent Application Publication No. WO 94 / 18317, WO96 / 20951, WO96 / 41865, WO99 / 1050 8, WO99 / 10510, WO99 / 36553, and WO99 / 41258, as well as No. 7,067,526 (disclosing rapamycin analogs) (which are incorporated herein by reference). (which is incorporated herein by reference for its disclosure of drug-inducible promoters). 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-1α binding site. In certain embodiments, the promoter comprises a HIF-2α binding site. The HIF binding site contains an RCGTG motif. Details regarding the location and sequence of the HIF binding site For example, see Schodel, et al., Blood, 2011, 117( 23):e207-e217, which is incorporated herein by reference in its entirety. In certain embodiments, the promoter is a hypoxia-inducible promoter other than a HIF transcription factor. In certain embodiments, the recombinant vectors provided herein contain binding sites for transcription factors. The vector contains one or more IRES sites that are preferentially translated under hypoxic conditions. For teachings regarding oxygen-induced gene expression and factors involved therein, see, e.g., Ken neth and Rocha,Biochem J.,2008,414:19-29 (incorporated herein by reference in its entirety).

[0138] In certain embodiments, the promoter is the CB7 promoter (Dincul escu et al.,2005,Hum Gene Ther 16:649-66 3, which is incorporated herein by reference in its entirety. In this configuration, the CB7 promoter enhances expression of the therapeutic product driven by the vector. Other expression control elements, such as (1) the CAG promoter; (2) the CBA promoter; (3) CMV promoter; (4) 1.7 kb red cone opsin promoter (P R1.7 promoter); (5) rhodopsin kinase (GRK1) photoreceptor-specific enzyme Hancer promoter (Young et al., 2003, Retinal Cell ll Biology;44:4076-4085);(6)hCARp promoter, (7) hRKp, which is the human cone arrestin promoter; (8) hRKp, which is the rhodopsin kinase promoter; (8) Cone photoreceptor-specific human arrestin 3 (ARR3) promoter (9) rhodopsin promoter; and (10) U6 promoter (especially therapeutic (where the intended product is a small RNA, e.g., shRNA or siRNA).

[0139] In certain embodiments, other expression control elements include chicken β-actin inserts. In certain embodiments, the poly(A) signal includes a poly(A) signal and / or a rabbit β-globin poly(A) signal. In certain embodiments, the promoter comprises a TATA box. In certain embodiments, one or more processes may be The motor elements may be reciprocal or translocatable relative to each other. In certain cases, promoter elements are arranged to function cooperatively. In this embodiment, the elements of the promoter are arranged to function independently. In certain embodiments, the recombinant vectors provided herein contain a human CMV immediate early gene. gene promoter, SV40 early promoter, Rous sarcoma virus (RS) long tail repeats, and one or more promoters selected from the group consisting of rat insulin promoter In certain embodiments, the recombinant vectors provided herein comprise an A promoter. From AV, MLV, MMTV, SV40, RSV, HIV-1, and HIV-2 LTRs The promoter comprises one or more long terminal repeat (LTR) promoters selected from the group consisting of: In certain embodiments, the recombinant vectors provided herein are capable of expressing one or more tissue-specific Certain promoters include heterologous promoters (e.g., retinal pigment epithelial cell-specific promoters). In embodiments, the recombinant vectors provided herein comprise an RPE65 promoter. In certain embodiments, the recombinant vectors provided herein comprise a VMD2 promoter. Includes.

[0140] In certain embodiments, the recombinant vectors provided herein contain a In certain embodiments, the nucleic acid sequence provided herein comprises one or more regulatory elements. The recombinant vector comprises an enhancer. In certain embodiments, the recombinant vector comprises an enhancer as provided herein. The recombinant vector comprises a repressor. In certain embodiments, the recombinant vector comprises a repressor as provided herein. The recombinant vector comprises an intron or a chimeric intron. The recombinant vectors provided herein contain polyadenylation sequences.

[0141] (e) signal peptide In certain embodiments, where the therapeutic product is a therapeutic protein, The recombinant vector comprises components that regulate protein delivery. The recombinant vectors provided herein contain one or more signal peptides. The signal peptide is also referred to herein as a "leader sequence" or "leader peptide." In certain embodiments, the signal peptide is used to ensure that the therapeutic product is properly packaged within the cell. This allows for caging (e.g., glycosylation) to be achieved. In this study, signal peptides enable therapeutic products to achieve proper localization within the cell. In certain embodiments, the signal peptide directs the therapeutic product to achieve secretion from the cell. In connection with the recombinant vectors and therapeutic products provided herein, Examples of signal peptides that may be used can be found in Table 1. Table 1. Signal peptides for use with the vectors provided herein. [Table 1]

[0142] (f) Polycistronic message—IRES and F2A linker Internal ribosome entry sites. A single construct can be constructed by combining two peptides (e.g., separate heavy and light chain polypeptides) are expressed by the transduced cells. Two peptides (e.g., both ends of an antibody) separated by a cleavable linker or IRES. In certain embodiments, the present invention can be engineered to encode a nucleotide sequence encoding a nucleotide sequence (heavy and light chains). The recombinant vectors provided herein may be polycistronic (e.g., bicistronic) For example, the recombinant vector may contain an internal ribosome entry site (IRES). Encodes two peptides (e.g., the heavy and light chains of an antibody) separated by an element (e.g., to create a bicistronic vector). Use of IRES elements for transfection, e.g., Gurtu et al., 1996, B Biochem.Biophys.Res.Comm.229(1):295-8 (reference (See, e.g., the entire contents of which are incorporated herein by reference). Bypassing the ribosome scanning model and initiating translation at internal sites. IRES in AAVs The use of is described, for example, in Furling et al., 2001, Gene Ther 8 (11):854-73, which is incorporated herein by reference in its entirety. In certain embodiments, the bicistronic message is contained within a recombinant vector. with restrictions on the size of the polynucleotide(s) therein. In embodiments, the bicistronic message is delivered via an AAV virus-based vector (e.g., For example, an AAV8-based vector.

[0143] Furin-F2A linker. In another embodiment, the recombinant vectors provided herein is linked by a cleavable linker, such as the self-cleaving furin / F2A (F / F2A) linker. The nucleotides encoding two peptides (e.g., the heavy and light chains of an antibody) are separated by (Fang et al., 2005, Nature Biotechnology logy 23:584-590, and Fang, 2007, Mol Ther 15: 1153-9 (each of which is incorporated herein by reference in its entirety).

[0144] For example, a furin-F2A linker can be incorporated into the expression cassette to express two peptides. Isolate the coding sequences (e.g., heavy and light chain coding sequences) to obtain the following: leader-peptide A (e.g., antibody heavy chain)-furin site-F2A site-leader - peptide B (e.g., antibody light chain) - poly A construct can be obtained. do.

[0145] F2 with the amino acid sequence LLNFDLLKLAGDVESNPGP (SEQ ID NO: 26) The A site is self-processing, resulting in a "cleavage" between the last G and P amino acid residues. Additional linkers that may be used include, but are not limited to: T2A:(GSG)EGRGSLLTCGDVEENP GP (SEQ ID NO: 27); P2A:(GSG)ATNFSLLKQAGDVEEN PGP (SEQ ID NO: 28); E2A:(GSG)QCTNYALLKLAGDVES NPGP (SEQ ID NO: 29); F2A:(GSG)VKQTLNFDLLKLAGDV ESNPGP (SEQ ID NO: 30).

[0146] When the ribosome encounters the F2A sequence in the open reading frame, it forms a peptide bond. The sequence is skipped and translation is terminated, or translation of the downstream sequence (second peptide) continues. This self-processing sequence is a series of additional amino acids at the C-terminal end of the first peptide. However, such additional amino acids are located immediately before and after the F2A site. The peptide sequence is followed by a furin site, which is cleaved by host cell furin. The resulting first peptide is then further cleaved by carboxypeptidase. The sequence of the furin linker used and the calcitonin that cleaves the linker in vivo are shown. Depending on the carboxypeptidase, one, two, three, or more may be present at the C-terminus. or may have no additional amino acids. (e.g., Fang et al., 17 April 2005, Nature Bi otechnol. Advance online publication; Fang et al., 2007, Mole cular therapy 15(6):1153-1159;Luke,2012, Innovations in Biotechnology,Ch.8,161-18 6). A furin linker that can be used is a series of four basic amino acids , for example, RKRR, RRRR, RRKR, or RKKR. Once this linker Upon cleavage by carboxypeptidase, additional amino acids may remain, resulting in 0, 1, 2, 3 or 4 additional amino acids, e.g., R, RR, RK, RKR, RRR , RRK, RKK, RKRR, RRRR, RRKR, or RKKR of the first peptide. In certain embodiments, once the linker is attached to the carboxypeptidase Upon cleavage by , no additional amino acids remain. The linker has the sequence RXK / RR and is connected to an additional amino acid on the C-terminus of the first peptide. The amino acid is R, RX, RXK, RXR, RXKR, or RXRR, where X is any amino acid, for example, alanine (A). In certain embodiments, the first No additional amino acids may remain on the C-terminus of the peptide.

[0147] In certain embodiments, the expression cassettes described herein are contained within a recombinant vector. and with restrictions on the size of the polynucleotide(s) therein. In embodiments, the expression cassette is contained in an AAV virus-based vector (e.g., an AAV8-based vector). The vector is contained within the

[0148] (g) Untranslated region In certain embodiments, where the therapeutic product is a therapeutic protein, The recombinant vector may contain one or more untranslated regions (UTRs), e.g., 3' and / or In certain embodiments, the UTR comprises a 5' UTR. In certain embodiments, the UTRs are optimized for encoding a therapeutic protein. In certain embodiments, the UTRs are optimized for the half-life of the mRNA they encode. , optimized for stability of mRNA encoding a therapeutic protein. In this embodiment, the UTRs are mutated with respect to the secondary structure of the mRNA encoding the therapeutic protein. It is optimized.

[0149] (h) inverted terminal repeats In certain embodiments, the recombinant viral vectors provided herein comprise one or It contains multiple inverted terminal repeat (ITR) sequences. The ITR sequences are used to construct recombinant therapeutic product expression cassettes. The kit can be used to package the vector into virions of a recombinant viral vector. In certain embodiments, the ITRs are derived from an AAV, e.g., AAV8 or AAV2. (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 B No. 2, 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). (see, e.g., the entirety of which is incorporated herein).

[0150] (i) Therapeutic Products Therapeutic products include, for example, therapeutic proteins (e.g., antibodies), therapeutic RNAs (e.g., shRNA, siRNA, and miRNA), or therapeutic aptamers. Antibodies include monoclonal antibodies, polyclonal antibodies, recombinantly produced antibodies, human antibodies, Humanized antibodies, chimeric antibodies, synthetic antibodies, tetrameric antibodies containing two heavy chain molecules and two light chain molecules antibody, antibody light chain monomer, antibody heavy chain monomer, antibody light chain dimer, antibody heavy chain dimer, antibody Light chain-heavy chain pairs, intrabodies, heteroconjugate antibodies, monovalent antibodies, and full-length antibody antigens These include, but are not limited to, binding fragments, as well as fusion proteins as described above. Such antigen-binding fragments include single domain antibodies (heavy chain antibodies (VHH) or nano-antibodies). variable domains of ribozymes), Fab, F(ab')2, and scFv (single-chain variable fragments) These include, but are not limited to:

[0151] In certain embodiments of the methods described herein, the therapeutic product comprises: (1) an anti-human intravascular (2) anti-hVEGF antigen-binding fragments; (3) an anti-hVEGF antigen-binding fragment, which may be Fab, F, or (ab')2, or single-chain variable fragment (scFv); (4) palmitoyl -Protein thioesterase 1 (PPT1); (5) Tripeptidyl-peptide (6) battenin (CLN3); (7) CLN6 transmembrane protein ER protein (CLN6); (8) major facilitator superfamily (9) myosin VIIA (MYO7A); (1) Cadherin-related 23 (CDH23); (11) Protocadherin-related 15 (12) Asherlin (USH2A); (13) Cla (14) ATP-binding cassette subfamily A member 4 (15) ELOVL fatty acid elongase 4 (ELOVL4) It is an anti-interleukin 6 (IL6) monoclonal antibody / aptamer; (16) Anti-TNF alpha (TNF) monoclonal antibody or aptamer; (17) L opsin (OPN1LW); (18) M opsin (OPN1MW); (19) Guanylate cyclase 2D, retinal (GUCY2D); (20) retinoid Somerohydrolase RPE65 (RPE65); (21) spermatogenesis-associated 7 (SPA TA7); (22) aryl hydrocarbon receptor-interacting protein-like 1 (AIPL1) ) (23) Reversillin (LCA5); (24) RPGR interacting protein (25) Cone-Rod Homeobox (CRX) (26) Crumbs cell polarity complex component 1 (CRB1); (27) Nicotine Namide nucleotide adenylyltransferase 1 (NMNAT1); (28 ) Centrosomal protein 290 (CEP290); (29) Inosine monophosphate dehydrogenase (3) retinal degeneration 3, GUCY2D regulator (RD3 ) (31) retinol dehydrogenase 12 (RDH12); (32) retinol dehydrogenase 12 (RDH12); (33) Tabby-like tan Protein 1 (TULP1); (34) Potassium voltage-gated channel subfamily J member 13 (KCNJ13); (35) mitochondrially encoded NADH dehydrogenase 1 (MT-ND1); (36) mitochondrially encoded N ADH dehydrogenase 4 (MT-ND4); (37) mitochondrially encoded NADH dehydrogenase 6 (MT-ND6); (38) anti-complement monoclonal antibody The anti-complement monoclonal antibody or aptamer is an anti-complement monoclonal antibody or aptamer. C1 antibody or aptamer, anti-complement C1q monoclonal antibody or aptamer, anti Complement C1s monoclonal antibody or aptamer, anti-complement C2 monoclonal antibody, or or aptamer, anti-complement C2a monoclonal antibody or aptamer, anti-complement C2b monoclonal antibody monoclonal antibody or aptamer, anti-complement C3 monoclonal antibody or aptamer -, anti-complement C3a monoclonal antibody or aptamer, anti-complement C3b monoclonal Antibody or aptamer, anti-complement C4 monoclonal antibody or aptamer, anti-complement C 4a monoclonal antibody or aptamer, anti-complement C4b monoclonal antibody or Aptamer, anti-complement C5 monoclonal antibody or aptamer, anti-complement C5a monoclonal antibody anti-complement C5b monoclonal antibody or aptamer; Anti-complement C6 monoclonal antibody or aptamer, anti-complement C7 monoclonal antibody, or or aptamer, anti-complement C8 monoclonal antibody or aptamer, or anti-complement C9 A monoclonal antibody or aptamer, or preferably an anti-complement C5 antibody, The pathology is associated with neuromyelitis optica (NMO); (39) anti-IL6 monoclonal antibodies or or aptamers, and ocular pathology associated with NMO; (40) anti-complement monoclonal Anti-complement monoclonal antibodies or aptamers are anti-complement C 1 Monoclonal antibody or aptamer, anti-complement C1q monoclonal antibody or aptamer Aptamer, anti-complement C1s monoclonal antibody or aptamer, anti-complement C2 monoclonal antibody monoclonal antibody or aptamer, anti-complement C2a monoclonal antibody or aptamer, anti Complement C2b monoclonal antibody or aptamer, anti-complement C3 monoclonal antibody, or or aptamer, anti-complement C3a monoclonal antibody or aptamer, anti-complement C3b monoclonal antibody monoclonal antibody or aptamer, anti-complement C4 monoclonal antibody or aptamer -, anti-complement C4a monoclonal antibody or aptamer, anti-complement C4b monoclonal Antibody or aptamer, anti-complement C5 monoclonal antibody or aptamer, anti-complement C 5a monoclonal antibody or aptamer, anti-complement C5b monoclonal antibody or Aptamer, anti-complement C6 monoclonal antibody or aptamer, anti-complement C7 monoclonal antibody anti-complement C8 monoclonal antibody or aptamer, or is an anti-complement C9 monoclonal antibody or aptamer, or preferably an anti-complement C5 antibody (41) angiotensin I converting enzyme (ACE); (42) interro IL10 (IL10); (43) anti-TNF monoclonal antibody; (43) Love escort protein 1 (CHM); (44) Retinoschisin (RS1) (45) Bardet-Biedl syndrome 1 (BBS1); (46) Bardet-Biedl (47) ADP-ribosylation factor-like GTPase 6 (ARL) syndrome 2 (BBS2); 6); (48) Bardet-Biedl syndrome 4 (BBS4); (49) Bardet- Biedl syndrome 5 (BBS5); (50) McKusick-Kaufman syndrome (M (51) Bardet-Biedl syndrome 7 (BBS7); (52) Tet Latricopeptide repeat domain 8 (TTC8); (53) Bardet-Biedl disease (54) Bardet-Biedl syndrome 10 (BBS10) (55) tripartite motif-containing 32 (TRIM32); (56) Bardet-Biedle (57) MKS Transition Zone Complex Syndrome 12 (BBS12) subunit 1 (MKS1); (58) WD repeat containing planar cell polarity ( (59) Serologically defined colon cancer antigen 8 (SDCCAG8) (6) leucine zipper transcription factor-like 1 (LZTFL1); (61) BBSo β-interacting protein 1 (BBIP1); (62) intraflagellar transport protein 27 (IFT27 ) ; (63) guanylate cyclase activator 1A (GUCA1A); (6 4) OPA1, a mitochondrial dynamin-like GTPase (OPA1); (65) RP1 is axonemal microtubule-associated (RP1);(66)RP2 activity of ARL3 GTPase (67) peripherin 2 (PRPH2); (68) mR Pre-mRNA processing factor 31 (PRPF31); (69) pre-mRNA processing factor sessing factor 8 (PRPF8); (70) EyeShut homolog (EYS) (71) FAM161 centrosomal protein A (FAM161A); (72) nuclear receptor NR2E3 is a member of the NR2 subfamily 2 group E family; (73)MER protozoan Oncogene, tyrosine kinase (MERTK); (74) phosphodiesterase 6B (PDE6B); (75) prominin 1 (PROM1); (76) phosphatase inhibitor Phosphodiesterase 6A (PDE6A); (77) Interphotoreceptor matrix protease glycan 2 (IMPG2); (78) male germ cell-associated kinase (MAK) (79) Intraflagellar transport 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 (84) Anti-beta-amyloid monoclonal antibody (85) CD59 glycoprotein (CD59); (86) channelrhodopsin-1 (87) Channelrhodopsin-2 (ChR2), (88) Anti Complement factor C5a aptamer or monoclonal antibody; (89) anti-complement factor D monoclonal antibody Clonal antibodies or aptamers; (90) DnaJ heat shock protein fragments family (Hsp40) member C3 (DNAJC3); (91) beta-2 adduct renal receptor siRNA; (92) caspase-2 (CASP2); (9 3) Insulin receptor substrate 1 (IRS1); (94) HIF-1 responsive protein RTP801 (RTP801); (95) Transforming growth factor beta 2 (TGFB2); (96) Brain-derived neurotrophic factor (BDNF); (97) Ciliary (98) Prostaglandin-endoperoxide (99) Prostaglandin F receptor 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) CC motif Chemokine receptor 5 (CCR5) siRNA; (106) anti-CD19 monoclonal antibody (107) Crumbs cell polarity complex component 2 (CRB) 2); (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 (113) Rod-derived cone survival factor (RDCVF) (114) Retinaldehyde-binding protein 1 (RLBP1); (115) Dub DUX4 (DUX4) is a NLR family member containing a pyrin domain. NLRP3 (NLRP3); (117) spleen-related tyrosine kinase (SYK); ( 118) Adrenocorticotropic hormone (ACTH); (119) Anti-CD59 monoclonal antibody (120) NOTCH-regulated ankyrin repeat protein (121) alpha-2-antiplasmin (A2AP) (122) plasminogen (PLG); (123) growth hormone; ( 124) Insulin-like growth factor 1 (IGF1); (125) Interleukin 1 beta (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 (130) Anti-insulin receptor (IGF1R) monoclonal antibody or aptamer; IGF2R monoclonal antibody or aptamer; 31) RTP801 siRNA; (132) Matrix metalloproteinase 2 (MMP2) RNAi; (133) G protein-coupled receptor 143 (GPR14 3); (134) tyrosinase (TYR); (135) anti-leucine-rich Pete and Ig domain-containing protein 1 (LINGO1) monoclonal antibody or antibody P (136) Retinitis pigmentosa GTPase regulator (RPGR) (137) Cyclic nucleotide-gated channel beta 3 (CNGB3); (13 8) Cyclic nucleotide-gated channel alpha 3 (CNGA3); (139) Retin (14) Anti-TNF Alpha or (140) interleukin 10 (I L10).

[0152] In certain embodiments of the methods described herein, (1) the ocular condition is a condition determined by the Batten-CL method. Related to N1, the therapeutic product is palmitoyl-protein thioesterase 1 (PPT1 (2) the ocular pathology is associated with Batten-CLN2 and the therapeutic product is a tripeptide (3) Ocular pathology is related to Batten-CLN3. The therapeutic product is Battenin (CLN3); (4) the eye condition is Batten-C Related to LN6, the therapeutic product is the CLN6 transmembrane ER protein (CLN6); 5) Ocular pathologies are associated with Batten-CLN7, and therapeutic products are key facilitators (6) Ocular pathology is caused by the chromatid superfamily domain containing 8 (MFSD8); associated with skeletal muscle syndrome type 1, and the therapeutic product is myosin VIIA (MYO7A); (7) The eye condition is associated with Usher syndrome type 1, and the therapeutic product is cadherin-related 23 (CD23). (8) The eye condition is associated with Usher syndrome type 2, and the therapeutic product is PCDH15 (rotocadherin-related 15); (9) Ocular pathology: Usher syndrome Associated with type 2, the therapeutic product is Usherin (USH2A); (10) Ocular pathology is associated with Usher syndrome type 3, and the therapeutic product is Clarrin 1 (CLRN1); (11) The eye condition is related to Stargardt's disease, and the therapeutic product is an ATP-binding cassette fragment. (12) Ocular pathology is a Stargardt-related Associated with the disease, the therapeutic product is ELOVL fatty acid elongase 4 (ELOVL4); (13) The ocular condition is related to uveitis, and the therapeutic product is an anti-interleukin 6 (IL-6) inhibitor. 6) Monoclonal antibodies; (14) Eye conditions related to uveitis, therapeutic products is an anti-TNF alpha (TNF) monoclonal antibody; (15) ocular pathology is diabetes Associated with pathological macular edema (DME), the therapeutic product is an anti-IL6 monoclonal antibody; (16) The eye condition is associated with red-green color blindness, and the therapeutic product is L opsin (OPN1LW). (17) An ocular condition associated with red-green color blindness, and a therapeutic product is a compound that inhibits M opsin (OPN1M (18) The eye condition is related to blue-cone monochromatism, and the therapeutic product is M-optimal. (19) The eye condition is Leber congenital amaurosis 1 (LCA 1 ) and the therapeutic product is guanylate cyclase 2D, retinal (GUCY2D) (20) The eye condition is related to Leber congenital amaurosis type 2 (LCA type 2), and therapeutic products The substance is retinoid isomerohydrolase RPE65 (RPE65); (21) ocular The pathology is associated with LCA 3 and the therapeutic product is spermatogenesis-associated 7 (SPATA7); (22) The eye condition is associated with Leber congenital amaurosis-4 (LCA 4), and the therapeutic product is Aryl hydrocarbon receptor-interacting protein-like 1 (AIPL1); (23) Eye disease The condition is associated with Leber congenital amaurosis-5 (LCA 5), and the therapeutic product is Reversilin ( (24) The eye condition is associated with Leber congenital amaurosis-6 (LCA 6). 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 a corn- Rod homeobox (CRX); (26) Eye pathology: 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 Leber congenital amaurosis-9 (LCA 9) and the therapeutic product is a nicotinamide nucleotide adenylyltran. (28) The eye condition is Leber congenital amaurosis-1 0 (LCA 10), and the therapeutic product is Centrosomal Protein 290 (CEP290) (29) The eye condition is related to Leber congenital amaurosis-11 (LCA 11) and is treatable. The therapeutic product is inosine monophosphate dehydrogenase 1 (IMPDH1); (30) ophthalmic The condition is associated with Leber congenital amaurosis-12 (LCA 12), and therapeutic products are used to treat retinal degeneration. 3, GUCY2D regulator (RD3); (31) eye pathology, Leber congenital amaurosis The therapeutic product inhibits retinol dehydrogenase 12 (LCA 13). (32) The eye condition is Leber congenital amaurosis-14 (LCA 14). In relation to the therapeutic product, the enzyme lecithin retinol acyltransferase (LRAT) (33) The eye condition is associated with Leber congenital amaurosis-15 (LCA 15) and is treatable. The product is tabby-like protein 1 (TULP1); (34) eye pathologies have been reported in Leber Congenital amaurosis-16 (LCA 16) is associated with the therapeutic product, which inhibits potassium voltage-gated channels. (35) Ocular pathology is a Levaline subfamily J member 13 (KCNJ13). -Related to hereditary optic neuropathy (LHON), the therapeutic product is a mitochondrially encoded NADH dehydrogenase 1 (MT-ND1); (36) Ocular pathology is associated with LHON. Related therapeutic products include mitochondrially encoded NADH dehydrogenase 4 (M (37) The eye condition is associated with LHON, and the therapeutic product is a mitochondrial MT-ND6 is a NADH dehydrogenase encoded by the ophthalmocyte The condition is associated with neuromyelitis optica (NMO), and the therapeutic product is an anti-complement antibody or anti-complement antigen. The anti-complement monoclonal antibody or aptamer is an anti-complement C1 antibody or is an aptamer, anti-complement C1q monoclonal antibody or an aptamer, anti-complement C1s monoclonal antibody Clonal antibody or aptamer, anti-complement C2 monoclonal antibody or aptamer , anti-complement C2a monoclonal antibody or aptamer, anti-complement C2b monoclonal antibody Monoclonal antibody or aptamer, anti-complement C3 a Monoclonal antibody or aptamer, anti-complement C3b monoclonal antibody or aptamer Aptamer, anti-complement C4 monoclonal antibody or aptamer, anti-complement C4a monoclonal antibody monoclonal antibody or aptamer, anti-complement C4b monoclonal antibody or aptamer, anti Complement C5 monoclonal antibody or aptamer, anti-complement C5a monoclonal antibody, or or aptamer, anti-complement C5b monoclonal antibody or aptamer, anti-complement C6 monoclonal antibody Clonal antibody or aptamer, anti-complement C7 monoclonal antibody or aptamer , anti-complement C8 monoclonal antibody or aptamer, or anti-complement C9 monoclonal (39) Ocular pathologies is associated with NMO, and the therapeutic product is an anti-IL6 monoclonal antibody or aptamer. (40) The eye condition is related to uveitis, and the therapeutic product is an anti-complement monoclonal antibody. The anti-complement monoclonal antibody or aptamer is an anti-complement C1 Monoclonal antibody or aptamer, anti-complement C1q monoclonal antibody or aptamer aptamer, anti-complement C1s monoclonal antibody or aptamer, anti-complement C2 monoclonal antibody monoclonal antibody or aptamer, anti-complement C2a monoclonal antibody or aptamer, anti-complement anti-complement C2b monoclonal antibody or aptamer, anti-complement C3 monoclonal antibody or is an aptamer, anti-complement C3a monoclonal antibody or an aptamer, anti-complement C3b monoclonal antibody Clonal antibody or aptamer, anti-complement C4 monoclonal antibody or aptamer , anti-complement C4a monoclonal antibody or aptamer, anti-complement C4b monoclonal antibody Monoclonal antibody or aptamer, anti-complement C5 a Monoclonal antibody or aptamer, anti-complement C5b monoclonal antibody or aptamer aptamer, anti-complement C6 monoclonal antibody or aptamer, anti-complement C7 monoclonal an anti-complement C8 monoclonal antibody or aptamer, an anti-complement C8 monoclonal antibody or aptamer, or Anti-complement C9 monoclonal antibody or aptamer, or preferably anti-complement C5 antibody (41) The eye condition is related to uveitis, and the therapeutic product is angiotensin I converting enzyme (ACE); (42) The eye condition is related to uveitis, and the therapeutic product is Interleukin 10 (IL10); (43) eye pathology related to uveitis, The therapeutic product is an anti-TNF monoclonal antibody; (44) the ocular pathology is choroideremia. The therapeutic product is love escort protein 1 (CHM); (45) eye The condition is associated with X-linked retinoschisis (XLRS), and the therapeutic product is retinoschisis (R S1); (46) The eye condition is associated with Bardet-Biedl syndrome 1, and the therapeutic product is , Bardet-Biedl syndrome 1 (BBS1); (47) ocular pathology, Bardet-Biedl Related to Biedl syndrome 2, the therapeutic product is Bardet-Biedl syndrome 2 (BBS2); 48) The ocular condition is associated with Bardet-Biedl syndrome 3, and the therapeutic product is ADP-ribosyltransferase. 49) ophthalmic factor-like GTPase 6 (ARL6) (also known as BBS3); The condition is associated with Bardet-Biedl syndrome, and the therapeutic product is 4 (BBS4); (50) an ocular condition associated with Bardet-Biedl syndrome 5, treatment The product is Bardet-Biedl syndrome 5 (BBS5); (51) the ocular pathology is Bardet-Biedl syndrome - Associated with Biedl syndrome6, the therapeutic product is used to treat McKusick-Kaufman syndrome (MK KS), also known as BBS6; (52) eye pathology, Bardet-Bidet Related to Biedl syndrome 7, the therapeutic product is Bardet-Biedl syndrome 7 (BBS7); 53) The eye condition is associated with Bardet-Biedl syndrome, and the therapeutic product is tetratrichopeol. Petidori repeat domain 8 (TTC8), also known as BBS8; (5 4) The eye condition is associated with Bardet-Biedl syndrome, and the therapeutic product is Syndrome 9 (BBS9); (55) ocular pathology related to Bardet-Biedl syndrome 10 The therapeutic product is Bardet-Biedl syndrome 10 (BBS10); (56) eye disease The condition is associated with Bardet-Biedl syndrome, and therapeutic products include tripartite motif-containing TRIM32), also known as BBS11; (57) eye pathologies Related to Bardet-Biedl syndrome 12, the therapeutic product is Bardet-Biedl syndrome 12 (BBS 12); (58) eye pathology associated with Bardet-Biedl syndrome 13, therapeutic products is the MKS transition zone complex subunit 1 (MKS1), It is also known as BBS13; (59) the ocular pathology is Bardet-Biedl syndrome 14. A related therapeutic product is centrosomal protein 290 (CEP290), which is a BBS Also known as LCA14 and LCA10; (60) an ocular condition called Bardet-Biedl syndrome 1 5, and the therapeutic product is a WD repeat containing planar cell polarity (WDPCP). (61) The ocular condition is Bardet-Biedl syndrome. 16, the therapeutic product is serologically defined colon cancer antigen 8 (SDCCAG8). (62) The eye condition is Bardet-Biedl syndrome. Related to Group 17, the therapeutic product is leucine zipper transcription factor-like 1 (LZTFL1). , also known as BBS17; (63) the ocular condition Bardet-Biedl syndrome 1 8, wherein the therapeutic product is BBSome-interacting protein 1 (BBIP1); This is also known as BBS18; (64) the ocular condition is Bardet-Biedl syndrome19 A related therapeutic product is intraflagellar transport 27 (IFT27), which is expressed as BBS19. (65) The eye condition is associated with cone dystrophy, and the therapeutic product is guaiamine. guanosine cyclase activator 1A (GUCA1A); (66) ocular pathology, optic nerve Associated with atrophy, therapeutic products inhibit the activity of OPA1, a mitochondrial dynamin-like GTPase (O P A1); (67) The eye condition is associated with retinitis pigmentosa 1, and the therapeutic product is RP1 Axonemal microtubule-associated (RP1); (68) ocular pathology associated with retinitis pigmentosa 2 and treatment The therapeutic product is the RP2 activator of ARL3 GTPase (RP2); (69) The condition is associated with retinitis pigmentosa7 and the therapeutic product is peripherin 2 (PRPH2). (70) The eye condition is associated with retinitis pigmentosa, and the therapeutic product is a precursor mRNA. Protein processing factor 31 (PRPF31); (71) eye pathology, retinitis pigmentosa 12, wherein the therapeutic product is Crumbs cell polarity complex component 1 (CRB1); It is also known as LCA8; (72) an eye condition associated with retinitis pigmentosa 13, The therapeutic product is pre-mRNA processing factor 8 (PRPF8); (73) ocular The condition is associated with retinitis pigmentosa 25, and the therapeutic product is EyeShut homolog (EYS). (74) The eye condition is associated with retinitis pigmentosa 28, and the therapeutic product is FAM 16. 1 Centrosomal protein A (FAM161A); (75) Ocular pathology: Retinitis pigmentosa 37, the therapeutic product is a nuclear receptor subfamily 2 group E member 3 (NR2 E3); (76) The eye condition is associated with retinitis pigmentosa 38, and the therapeutic product is ME R proto-oncogene tyrosine kinase (MERTK); (77) Ocular pathology Retinitis pigmentosa 40 is associated with the therapeutic product phosphodiesterase 6B (PDE6B) (78) The eye condition is associated with retinitis pigmentosa, and the therapeutic product is prominence. 1 (PROM1); (79) an ocular condition associated with retinitis pigmentosa43, and therapeutic production The substance is phosphodiesterase 6A (PDE6A); (80) eye pathology is retinal pigment epithelium The therapeutic product is interphotoreceptor matrix proteoglycan 2 (IM) associated with degeneration56. PG2); (81) The eye condition is associated with retinitis pigmentosa62, and the therapeutic product is 82) Ocular pathology is associated with retinitis pigmentosa 80. A related therapeutic product is intraflagellar transporter 140 (IFT140); (83) ocular pathologies , associated with dry AMD, and the therapeutic product is an anti-complement monoclonal antibody or anti-complement aptamer. and the anti-complement monoclonal antibody or anti-complement aptamer is an anti-complement C1 monoclonal antibody. anti-complement C1q monoclonal antibody or aptamer; Anti-complement C1s monoclonal antibody or aptamer, anti-complement C2 monoclonal antibody or aptamer, anti-complement C2a monoclonal antibody or aptamer, anti-complement C2b Monoclonal antibody or aptamer, anti-complement C3 monoclonal antibody or aptamer Anti-complement C3a monoclonal antibody or aptamer, anti-complement C3b monoclonal antibody monoclonal antibody or aptamer, anti-complement C4 monoclonal antibody or aptamer, anti-complement C4a monoclonal antibody or aptamer, anti-complement C4b monoclonal antibody or aptamer, anti-complement C5 monoclonal antibody or aptamer, anti-complement C5a monoclonal antibody monoclonal antibody or aptamer, anti-complement C5b monoclonal antibody or aptamer , anti-complement C6 monoclonal antibody or aptamer, anti-complement C7 monoclonal antibody or aptamer, anti-complement C8 monoclonal antibody or aptamer, or anti-complement C 9 monoclonal antibody or aptamer, or preferably an anti-complement C5 antibody; (84) The ocular pathology is associated with dry AMD, and the therapeutic product is the anti-membrane attack complex (MAC). The therapeutic product, preferably an anti-MAC therapeutic product, is an anti-MAC monoclonal antibody. This is a monoclonal antibody against a human protein of the membrane attack complex, which The invasion complex is composed of four complement proteins: C5b (SEQ ID NOs: 314-316), C6 (SEQ ID NOs: 317-319), C7 (SEQ ID NO: 317), C7 (SEQ ID NO: 318), and C8 (SEQ ID NOs: 319-321) (85) The ocular pathology is associated with dry AMD, and the therapeutic product inhibits the HtrA serine peptide. (86) Ocular pathology associated with Best's disease, therapeutic product bestrophin 1 (BEST1); (87) an ocular pathology associated with dry AMD. The therapeutic product is a complement factor B antisense oligonucleotide; (88) eye disease The condition is associated with dry AMD, and the therapeutic product is an anti-beta-amyloid monoclonal antibody. (89) The ocular pathology is associated with dry AMD, and the therapeutic product inhibits the CD59 glycoprotein. (90) The ocular pathology is associated with dry AMD, and the therapeutic product is Channelrhodopsin-1 (ChR1), which contains the human homolog of ChR1; 91) The ocular pathology is associated with dry AMD, and the therapeutic product is channelrhodopsin-2 (C hR2), which contains the human homolog of ChR2; (92) the ocular pathology is dry type A In relation to MD, the therapeutic product is an anti-complement monoclonal antibody or an anti-complement aptamer. , anti-complement monoclonal antibody or anti-complement aptamer, anti-complement C1 monoclonal antibody or aptamer, anti-complement C1q monoclonal antibody or aptamer, anti-complement C1 s Monoclonal antibody or aptamer, anti-complement C2 monoclonal antibody or aptamer aptamer, anti-complement C2a monoclonal antibody or aptamer, anti-complement C2b monoclonal antibody monoclonal antibody or aptamer, anti-complement C3 monoclonal antibody or aptamer, anti-complement Anti-complement C3a monoclonal antibody or aptamer, anti-complement C3b monoclonal antibody or or aptamer, anti-complement C4 monoclonal antibody or aptamer, anti-complement C4a monoclonal antibody Clonal antibody or aptamer, anti-complement C4b monoclonal antibody or aptamer -, anti-complement C5 monoclonal antibody or aptamer, anti-complement C5a monoclonal antibody Anti-complement C5b monoclonal antibody or aptamer, anti-complement C 6 Monoclonal antibody or aptamer, anti-complement C7 monoclonal antibody or aptamer tamer, anti-complement C8 monoclonal antibody or aptamer, or anti-complement C9 monoclonal antibody (93) a monoclonal antibody or aptamer, or preferably an anti-complement C5 antibody; The condition is associated with dry AMD, and the therapeutic product is an anti-complement factor D therapeutic product, which These include anti-complement factor D monoclonal antibodies or anti-complement factor D aptamers. (94) Ocular pathologies include, but are not limited to, age-related retinal ganglion cell (RGC) degeneration. In this context, therapeutic products are directed to members of the DnaJ heat shock protein family (Hsp40). Bar C3 (DNAJC3), also known as P58IPK; (95) ocular The condition is associated with blue-cone monochromatism (BCM), and the therapeutic product is a blocker for L-opsin (OPN1L (96) The eye condition is related to glaucoma, and the therapeutic product is a beta-2 adrenergic receptor antagonist. (97) The eye condition is related to glaucoma, and the therapeutic product is a phospholipase C receptor siRNA; cataract surgery-2 (CASP2); (98) an ocular condition associated with glaucoma, and therapeutic products is insulin receptor substrate 1 (IRS1); (99) ocular pathology associated with glaucoma , the therapeutic product is the HIF-1 responsive protein RTP801 (RTP801); 100) The eye condition is related to glaucoma, and the therapeutic product is a transforming growth factor-based (101) The eye condition is related to glaucoma, and the therapeutic product is Brain-derived neurotrophic factor (BDNF); (102) an ocular condition related to glaucoma and its treatment The product is ciliary neurotrophic factor (CNTF); (103) the ocular pathology is related to glaucoma. In this context, the therapeutic product is a prostaglandin-endoperoxide synthase 2 (PTGS 2) inhibitor. 2); (104) The eye condition is related to glaucoma, and the therapeutic product is a prostaglandin. and a phospholipid receptor (PTGFR) (in certain embodiments, when the ocular condition is related to glaucoma). The present invention provides a method for administering a recombinant viral vector containing a nucleotide sequence encoding a PTGFR to a human subject. , in combination with a recombinant viral vector containing a nucleotide sequence encoding PTGS2. In another specific embodiment, the nucleotide sequence encoding the PTGFR can be administered. a recombinant viral vector comprising a nucleotide sequence encoding the PTGS2 gene and a nucleotide sequence encoding the PTGS2 gene, (105) The eye condition is related to glaucoma and is a therapeutic product. The substance is a hyaluronidase, e.g., HYAL1, HYAL2, HYAL3, HYAL4, and HYAL5; (106) the eye condition is related to glaucoma, and the therapeutic product is a pigment- Physiologically, the ocular condition is associated with glaucoma, and therapeutic products include , vascular endothelial growth factor (VEGF); (108) eye conditions related to glaucoma and treatment The product used is placenta growth factor (PGF), which can be used in combination with VEGF. (109) Ocular conditions include glaucoma (e.g., congenital or juvenile glaucoma) ), and the therapeutic product is myocilin (MYOC); (110) eye pathologies are In relation to MO, the therapeutic product is an anti-complement C5 monoclonal antibody; (111) Eye disease The condition is associated with NMO, and the therapeutic product binds to the CC motif chemokine receptor 5 (CCR5) siRNA, CCR5 shRNA, siRNA or CCR5 miRNA (preferably (112) Ocular pathology is associated with NMO and is a therapeutic product. The substance is an anti-CD19 monoclonal antibody; (113) The pathology of the eye is rhodopsin mutation. The therapeutic product is associated with retinitis pigmentosa with dysregulation of channelrhodopsin-1 (ChR1). , which contains the human homolog of ChR1; (114) ocular pathologies are associated with rhodopsin abruption. Therapeutic products are associated with retinitis pigmentosa with mutations in channelrhodopsin-2 (ChR2 ), which contains the human homolog of ChR2; (115) ocular pathology, retinitis pigmentosa The therapeutic product is ciliary neurotrophic factor (CNTF); (116) eye disease The condition is associated with autosomal recessive retinitis pigmentosa, and the therapeutic product inhibits the Crumbs cell polarity complex. (117) Ocular pathology is associated with autosomal recessive retinitis pigmentosa. In this context, the therapeutic product is Crumbs cell polarity complex component 2 (CRB2); (118 ) eye condition associated with retinitis pigmentosa, and therapeutic products inhibit histone deacetylase 4 ( (119) The eye condition is related to retinitis pigmentosa, and the therapeutic product is rhodopsin (RHO); (120) an ocular condition related to retinitis pigmentosa, The product is nerve growth factor (NGF); (121) an ocular condition associated with retinitis pigmentosa The therapeutic product is nuclear factor erythroid 2-like 2 (NRF2); (122) ocular pathologies include Associated with retinitis pigmentosa, the therapeutic product is pigment epithelium-derived factor (PEDF); (12 3) The eye condition is related to retinitis pigmentosa, and the therapeutic product is glutathione S-transferase. PI1 (GSTP1), also known as PI; (124) Eye disease The condition is associated with retinitis pigmentosa, and the therapeutic product is rod-derived cone survival factor (RDCVF). (125) The eye condition is related to retinitis pigmentosa, and the therapeutic product is rhodopsin (R HO); (126) The eye condition is related to retinitis pigmentosa, and the therapeutic product is a retinoid. Aldehyde-binding protein 1 (RLBP1); (127) Ocular pathology is In relation to rheumatoid arthritis, the therapeutic product is an anti-complement C5 aptamer; (128) ocular pathologies include The therapeutic product involved in uveitis is double homeobox 4 (DUX4); (1 29) The eye condition is related to uveitis, and the therapeutic product is an NLR family pyrimidine dehydrogenase (NLR) inhibitor. 130 The ocular pathology is associated with uveitis and is a therapeutic product. The substance is spleen-associated tyrosine kinase (SYK); (131) eye pathology is uveitis The therapeutic product is adrenocorticotropic hormone (ACTH); (132) eye diseases The condition is associated with uveitis, and the therapeutic product is caspase 1 (CASP1); (13 3 The ocular condition is associated with uveitis, and the therapeutic product is an anti-CD59 therapeutic product (e.g., an anti-C CD59 therapeutic protein (e.g., anti-CD59 monoclonal antibody), or anti-CD59 Therapeutic RNA (e.g., anti-CD59 shRNA, anti-CD59 siRNA, or anti-CD59 CD59 miRNA), preferably an anti-CD59 monoclonal antibody); (134) The ocular condition is related to uveitis, and the therapeutic product is an anti-complement monoclonal antibody or anti-complement The anti-complement monoclonal antibody or aptamer is an anti-complement C1 monoclonal antibody. monoclonal antibody or aptamer, anti-complement C1q monoclonal antibody or aptamer , anti-complement C1s monoclonal antibody or aptamer, anti-complement C2 monoclonal antibody or aptamer, anti-complement C2a monoclonal antibody or aptamer, anti-complement C2 b Monoclonal antibody or aptamer, anti-complement C3 monoclonal antibody or aptamer aptamer, anti-complement C3a monoclonal antibody or aptamer, anti-complement C3b monoclonal antibody monoclonal antibody or aptamer, anti-complement C4 monoclonal antibody or aptamer, anti-complement Anti-complement C4a monoclonal antibody or aptamer, anti-complement C4b monoclonal antibody or or aptamer, anti-complement C5 monoclonal antibody or aptamer, anti-complement C5a monoclonal antibody Clonal antibody or aptamer, anti-complement C5b monoclonal antibody or aptamer -, anti-complement C6 monoclonal antibody or aptamer, anti-complement C7 monoclonal antibody or aptamer, anti-complement C8 monoclonal antibody or aptamer, or anti-complement C9 monoclonal antibody or aptamer, or preferably an anti-complement C5 antibody (135) The ocular pathology is associated with corneal neovascularization, and the therapeutic product is an insulin receptor substrate. 1 (IRS1); (136) The ocular pathology is related to corneal neovascularization, and the therapeutic product is NOTCH-regulated ankyrin repeat protein (NRARP); (137) Eye disease The condition is associated with diabetic retinopathy, and the therapeutic product is a NOTCH-regulated ankyrin repeat protein. 138 The ocular pathology is related to diabetic retinopathy and is a therapeutic The product is alpha-2-antiplasmin (A2AP); (139) Ocular pathologies include The therapeutic product involved in diabetic retinopathy is plasminogen (PLG); (140 The ocular condition may be associated with diabetic retinopathy and the therapeutic product may be growth hormone. (141) The eye condition is related to diabetic retinopathy, and the therapeutic product acts as an insulin-like growth factor. Growth hormone (IGF1) is a growth factor that can be used in combination with growth hormone. (142) The eye condition is related to diabetic retinopathy, and the therapeutic product is interleukin (IL). 1 beta (IL1B). (143) Ocular pathology is associated with diabetic retinopathy and is a therapeutic The product is angiotensin I-converting enzyme 2 (ACE2), which combines with IL1B. (144) Eye conditions related to diabetic retinopathy and treatment The therapeutic product is IRS1; (145) the ocular pathology is associated with diabetic retinopathy, The substance is an anti-integrin oligopeptide; (146) ocular pathology is diabetic retinopathy. A related therapeutic product is an anti-placental growth factor (PGF) monoclonal antibody; (147 ) eye condition associated with Graves' ophthalmopathy (also known as Graves' orbitopathy) and therapeutic The product is an anti-CD40 monoclonal antibody; (148) the ocular condition is Graves' ophthalmopathy. In accordance with the present invention, 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 therapeutic products are anti-insulin antibodies. IGF2R monoclonal antibody; (150) Eye disease The condition is associated with DME and the therapeutic product is an anti-integrin oligopeptide; The eye condition is associated with DME, and the therapeutic product is an anti-placental growth factor (PGF) monoclonal antibody. (152) The ocular condition is associated with DME, and the therapeutic product is RTP801. 153 Ocular pathology associated with multiple sclerosis (MS)-related visual loss. and the therapeutic product is ND1; (154) the eye condition is related to myopia and the therapeutic product is , matrix metalloproteinase 2 (MMP2) RNAi; (155) eye disease The condition is associated with X-linked recessive ocular albinism, and the therapeutic product inhibits the G protein-coupled receptor 143 (G PR143); (156) The eye condition is associated with oculocutaneous albinism type 1, and the therapeutic product is , tyrosinase (TYR); (157) Ocular pathology is associated with optic neuritis, and therapeutic production The substance is caspase 2 (CASP2); (158) eye pathology is associated with optic neuritis, The therapeutic product is anti-leucine-rich repeat and Ig domain-containing protein 1 (LING) O1) It is a monoclonal antibody; or (159) The ocular condition is polypoidal choroidal hemorrhage. In relation to vasculopathy, the therapeutic product is an anti-complement monoclonal antibody or an anti-complement aptamer. The anti-complement monoclonal antibody or aptamer is an anti-complement C1 monoclonal antibody or Aptamers, anti-complement C1q monoclonal antibodies / aptamers, anti-complement C1s monoclonal antibodies Monoclonal antibody / aptamer, anti-complement C2 monoclonal antibody / aptamer, anti-complement C2a monoclonal antibody Clonal antibody or aptamer, anti-complement C2b monoclonal antibody or aptamer -, anti-complement C3 monoclonal antibody or aptamer, anti-complement C3a monoclonal antibody Anti-complement C3b monoclonal antibody or aptamer, anti-complement C 4 monoclonal antibody or aptamer, anti-complement C4a monoclonal antibody or aptamer Aptamer, anti-complement C4b monoclonal antibody or aptamer, anti-complement C5 monoclonal antibody monoclonal antibody or aptamer, anti-complement C5a monoclonal antibody or aptamer, anti Complement C5b monoclonal antibody or aptamer, anti-complement C6 monoclonal antibody, or or aptamer, anti-complement C7 monoclonal antibody or aptamer, anti-complement C8 monoclonal antibody monoclonal antibody or aptamer, or anti-complement C9 monoclonal antibody or aptamer or preferably an anti-complement C5 antibody.

[0153] In certain embodiments of the methods described herein, the ocular condition is X-linked retinitis pigmentosa. (XLRP), and the therapeutic product is retinitis pigmentosa GTPase regulator (R In certain embodiments of any of the foregoing methods, the ocular condition is color vision deficiency. The therapeutic product is a cyclic nucleotide-gated channel beta 3 (C In certain embodiments of any of the foregoing methods, the ocular condition is color vision impairment. associated with disorders (e.g., CNGA3-linked color blindness), and the therapeutic product is a cyclic nucleotide and CNGA3. Certain implementations of any of the foregoing methods In morphology, the ocular pathology is associated with biallelic RPE65 mutation-associated retinal dystrophy. The therapeutic product is retinoid isomerohydrolase RPE65 (RPE65).

[0154] In certain embodiments of the methods described herein, (1) the ocular condition is a condition determined by the Batten-CL method. Related to N1, the therapeutic product is palmitoyl-protein thioesterase 1 (PPT1 (2) the ocular pathology is associated with Batten-CLN2 and the therapeutic product is a tripeptide (3) Ocular pathology is related to Batten-CLN3. The therapeutic product is battenin (CLN3); (4) the ocular condition is uveitis. Related therapeutic products are anti-interleukin 6 (IL6) monoclonal antibodies; 5) the ocular condition is associated with uveitis and the therapeutic product is an anti-TNF alpha (TNF) monoclonal antibody; (6) an ocular condition related to diabetic macular edema (DME) and its treatment The product is an anti-IL6 monoclonal antibody; (7) the ocular condition is associated with red-green color blindness; The therapeutic product is L opsin (OPN1LW); (8) an ocular condition associated with red-green color blindness. The therapeutic product is M opsin (OPN1MW); (9) the ocular pathology is blue cone monochromatic. Related to color vision, the therapeutic product is M opsin (OPN1MW); (10) Ophthalmic pathology is associated with Leber congenital amaurosis-1 (LCA 1), and the therapeutic product is a guanylate cyclase. (11) The eye condition is Leber's congenital amaurosis The therapeutic product inhibits retinoid isomerohydrolase RPE 65 (RPE65); (12) the eye condition is Leber congenital amaurosis-7 (LCA 7 ), and the therapeutic product is the cone-rod homeobox (CRX); (13) The eye condition is associated with Leber congenital amaurosis-11 (LCA 11), and therapeutic products are (14) Ocular pathology is a rare condition that affects the immune system. -Related to congenital amaurosis-12 (LCA 12), therapeutic products include retinal degeneration 3, GUCY 2 (15) The eye condition is Leber congenital amaurosis-13 (LCA). 13), and the therapeutic product is retinol dehydrogenase 12 (RDH12). (16) The eye condition is related to Leber congenital amaurosis-15 (LCA 15) and is therapeutically The product is tabby-like protein 1 (TULP1); (17) eye pathology has been reported by Leber et al. Related to LCA 16, the therapeutic product is a potassium voltage-gated channel subfamily J member 13 (KCNJ13); (18) eye pathology The therapeutic product is a mitochondrially encoded N ADH dehydrogenase 1 (MT-ND1); (19) Ocular pathology is associated with LHON. In this context, the therapeutic product inhibits the mitochondrially encoded NADH dehydrogenase 4 (MT (20) The eye condition is associated with LHON, and the therapeutic product acts on the mitochondrion. NADH dehydrogenase 6 (MT-ND6) encoded by the retina; (21) the eye The condition is associated with neuromyelitis optica (NMO) and therapeutic products include anti-complement monoclonal antibodies or or anti-complement aptamer, and the anti-complement monoclonal antibody or aptamer is an anti-complement C 1 Monoclonal antibody or aptamer, anti-complement C1q monoclonal antibody or aptamer Aptamer, anti-complement C1s monoclonal antibody or aptamer, anti-complement C2 monoclonal antibody monoclonal antibody or aptamer, anti-complement C2a monoclonal antibody or aptamer, anti Complement C2b monoclonal antibody or aptamer, anti-complement C3 monoclonal antibody, or or aptamer, anti-complement C3a monoclonal antibody or aptamer, anti-complement C3b monoclonal antibody monoclonal antibody or aptamer, anti-complement C4 monoclonal antibody or aptamer -, anti-complement C4a monoclonal antibody or aptamer, anti-complement C4b monoclonal Antibody or aptamer, anti-complement C5 monoclonal antibody or aptamer, anti-complement C 5a monoclonal antibody or aptamer, anti-complement C5b monoclonal antibody or Aptamer, anti-complement C6 monoclonal antibody or aptamer, anti-complement C7 monoclonal antibody anti-complement C8 monoclonal antibody or aptamer, or is an anti-complement C9 monoclonal antibody or aptamer, or preferably an anti-complement C5 antibody (22) Ocular pathology is associated with NMO, and therapeutic products include anti-IL6 monoclonal antibodies. (23) The ocular condition is associated with uveitis, and the therapeutic product is an anti-complement C5 monoclonal antibody. (24) The ocular condition is related to uveitis, and the therapeutic product is an angiotensin I-converting enzyme (ACE); (25) ocular pathology associated with uveitis The therapeutic product is interleukin 10 (IL10); (26) eye conditions include bud In relation to uveitis, the therapeutic product is an anti-TNF monoclonal antibody; (27) Ocular pathology is associated with X-linked retinoschisis (XLRS), and the therapeutic product is retinoschisin (RS1) (28) The eye condition is associated with Bardet-Biedl syndrome, and the therapeutic product is Bardet-Biedl syndrome 1 (BBS1); (29) the eye condition is Bardet-Biedl syndrome Related to group 3, the therapeutic product is ADP-ribosylation factor-like GTPase 6 (ARL6). (30) The eye condition is associated with Bardet-Biedl syndrome, and the therapeutic product is Biedl syndrome 5 (BBS5); (31) ocular pathology is Bardet-Biedl syndrome 6 The therapeutic product is McKusick-Kaufman syndrome (MKKS); 2) The eye condition is associated with Bardet-Biedl syndrome, and the therapeutic product is (33) Ocular pathology is Bardet-Biedl syndrome 11 (BBS10). The therapeutic product is tripartite motif-containing 32 (TRIM32); (34) ophthalmic The condition is associated with Bardet-Biedl syndrome13 and therapeutic products are used to treat MKS transitions. Zone complex subunit 1 (MKS1); (35) Ocular pathology -Associated with Biedl syndrome18, the therapeutic product is BBSome interacting protein 1 (B BIP1); (36) the eye condition is associated with Bardet-Biedl syndrome19 and is therapeutically The product is intraflagellar transporter 27 (IFT27); (37) the ocular pathology is cone dystrophy. The therapeutic product is guanylate cyclase activator 1A (GUCA1A). (38) The eye condition is associated with retinitis pigmentosa 13, and the therapeutic product is a precursor mRNA. (39) Ocular pathology is associated with retinitis pigmentosa (37). Related therapeutic products include nuclear receptor subfamily 2 group E member 3 (NR2E3) or (40) the ocular condition is associated with Best's disease and the therapeutic product is a Bestrophin. It is No. 1 (BEST1).

[0155] In certain embodiments of the methods described herein, the ocular condition is characterized by biallelic RPE6 5 mutation-associated retinal dystrophies, and therapeutic products include retinoid isomerohydrochlorides. The enzyme is RPE65 (RPE65).

[0156] In certain embodiments of the methods described herein, (1) the ocular condition is a condition determined by the Batten-CL method. Related to N2, the therapeutic product is tripeptidyl-peptidase 1 (TPP1); 2) The eye condition is associated with Usher syndrome type 1, and the therapeutic product is myosin VIIA (M YO7A); (3) the eye condition is associated with Usher syndrome type 1, and the therapeutic product is cadherin-related 23 (CDH23); (4) eye pathology is associated with Usher syndrome type 2 A related therapeutic product is protocadherin-related 15 (PCDH15); (5) ocular The condition is associated with Usher syndrome type 2, and the therapeutic product is Usherin (USH2A). (6) The eye condition is associated with Usher syndrome type 3, and the therapeutic product is Curaline 1. (CLRN1); (7) the eye condition is associated with Stargardt's disease, and the therapeutic product is ATP-binding cassette subfamily A member 4 (ABCA4); (8) ocular pathology is associated with Stargardt disease, and the therapeutic product inhibits ELOVL fatty acid elongase 4 (EL OVL4); (9) The ocular condition is associated with red-green color blindness, and the therapeutic p...

Claims

1. A method of subretinal administration without vitrectomy for treating ocular conditions, comprising administering the same to a subject requiring treatment. and administering to the subretinal space of the eye of a human subject a composition comprising a nucleotide sequence encoding a therapeutic product. and administering a recombinant viral vector to express the therapeutic product and treat the condition of the eye. and the method does not include performing a vitrectomy on the eye of the human patient.

2. The administering step comprises administering to the subretinal space of the eye of the human subject via the suprachoroidal space of the eye of the human subject.

2. The method of claim 1, comprising administering the recombinant viral vector therapeutic product to a mammalian animal. Law.

3. The administering step can insert into the suprachoroidal space and pass through the suprachoroidal space toward the posterior pole. , for use of a subretinal drug delivery device including a catheter for injecting a fine needle into the subretinal space at the posterior pole. The method of claim 2, wherein

4. The administering step includes inserting the catheter of the subretinal drug delivery device into the suprachoroidal space.

4. The method of claim 3, comprising: passing the catheter through the suprachoroidal space.

5. A method of suprachoroidal administration for treating an ocular condition, comprising administering to a human subject in need thereof The suprachoroidal space of the eye is injected with a recombinant viral vector containing a nucleotide sequence encoding a therapeutic product. administering a therapeutic agent to the subject to express said therapeutic product, resulting in treatment of said ocular condition. , the method.

6. The administration step delivers the recombinant viral vector to the suprachoroidal space as a suprachoroidal drug delivery device.

6. The method of claim 5, wherein the injection is by using a vise.

7. 10. The method of claim 5, wherein the suprachoroidal drug delivery device is a microinjector. The method described below.

8. A method of administration to the extrascleral space for treating an ocular condition, comprising administering to a subject in need of treatment a recombinant human ophthalmic solution containing a nucleotide sequence encoding a therapeutic product, the recombinant human ophthalmic solution being attached to the outer surface of the sclera of the subject's eye; administering a viral vector to express said therapeutic product and result in treatment of said ocular condition; The method, comprising:

9. The administering step may include inserting the tip of the cannula into the scleral surface and placing it directly in apposition to the scleral surface. and by use of a juxtascleral drug delivery device including a cannula capable of 8. The method according to claim 8.

10. The administration step includes inserting the tip of the cannula into the scleral surface and directly administering the cannula to the scleral surface.

10. The method of claim 9, comprising juxtaposing.

11. The therapeutic product according to claims 1 to 5, wherein the therapeutic product is not an anti-human vascular endothelial growth factor (hVEGF) antibody.

11. The method according to any one of claims 10 to 10.

12. 1. The method of claim 1, wherein the ocular condition is not associated with neovascular age-related macular degeneration (nAMD).

1. The method according to any one of claims 1 to 9.

13. A method of subretinal administration with vitrectomy for treating an ocular condition, comprising administering to a subject in need of treatment a recombinant human subject comprising a nucleotide sequence encoding a therapeutic product, the recombinant human subject being administered a therapeutic product into the subretinal space of the eye of the subject. administering a viral vector to express said therapeutic product and result in treatment of said ocular condition; and performing a vitrectomy on the eye of the human patient, wherein the therapeutic product comprises an anti-inflammatory drug. The method, wherein the antibody is not a human vascular endothelial growth factor (hVEGF) antibody.

14. The method of claim 13 , wherein the vitrectomy is a partial vitrectomy.

15. A method of subretinal administration for treating an ocular condition, comprising administering the same to a human subject in need thereof. The subretinal space around the optic disc, fovea, and macula, located in the eye, is filled with a substance that encodes a therapeutic product. and administering a recombinant viral vector containing a nucleotide sequence to express said therapeutic product. and performing a vitrectomy on the eye of said human patient, resulting in treatment of said condition of the eye. and

16. 16. The method of claim 15, wherein the administering step is by intravitreal injection.

17. The transvitreal injection is performed by inserting a sharp needle into the sclera via the upper or lower eye side, and then inserting the sharp needle into the vitreous. The recombinant viral vector is then injected into the subretinal space on the opposite side, allowing it to pass completely through the retina. The method of claim 16, comprising:

18. The transvitreal injection is performed by inserting a trocar into the sclera, inserting a cannula into the trocar, and injecting the vitreous and injecting the recombinant viral vector into the contralateral subretinal space via a Item 17. The method according to item 16.

19. The therapeutic product according to any one of claims 15 to 18, wherein the therapeutic product is an anti-hVEGF antibody. How to do it.

20. 20. The method of claim 19, wherein the anti-hVEGF antibody is an anti-hVEGF antigen-binding fragment. How to post.

21. The anti-hVEGF antigen-binding fragment may be Fab, F(ab'), ２ , or single-stranded The method of claim 20, wherein the antibody is a scFv fragment.

22. 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.

10. The method according to any one of claims 1 to 9.

23. The anti-hVEGF antibody comprises a light chain CDR1-3 of SEQ ID NO: 14-16 and a light chain CDR1-3 of SEQ ID NO: 1 7 to 19 or SEQ ID NOs: 20, 18, and 21.

22. The method according to any one of claims 21 to 21.

24. The eye condition is nAMD, dry age-related macular degeneration (dry AMD), retinal vein occlusion, associated with renal oedema (RVO), diabetic macular edema (DME), or diabetic retinopathy (DR) The method according to any one of claims 19 to 23.

25. The method of any one of claims 19 to 23, wherein the eye condition is associated with nAMD. 。

26. (1) The ocular condition is associated with Batten-CLN1 and the therapeutic product is palmitoyl leu - protein thioesterase 1 (PPT1); (2) The ocular condition is associated with Batten-CLN2, and the therapeutic product is a tripeptide. leu-peptidase 1 (TPP1); (3) The ocular condition is associated with Batten-CLN3, and the therapeutic product is a battenin ( CLN3); (4) The ocular condition is associated with Batten-CLN6, and the therapeutic product is a CLN6 transmembrane inhibitor. a common ER protein (CLN6); (5) The eye condition is associated with Batten-CLN7, and the therapeutic product inhibits the major fascicles. tator superfamily domain containing 8 (MFSD8); (6) The eye condition is associated with Usher syndrome type 1, and the therapeutic product is myosin V. IIA (MYO7A); (7) The eye condition is associated with Usher syndrome type 1, and the therapeutic product is a cadherin Related 23 (CDH23); (8) The eye condition is associated with Usher syndrome type 2, and the therapeutic product is a protocade. herin-related 15 (PCDH15); (9) The eye condition is associated with Usher syndrome type 2, and the therapeutic product is phosphorus (USH2A); (10) The eye condition is associated with Usher syndrome type 3 and the therapeutic product is clarinet. 1 (CLRN1); (11) The eye condition is associated with Stargardt's disease, and the therapeutic product is an ATP-binding protein. Set subfamily A member 4 (ABCA4); (12) The eye condition is associated with Stargardt's disease, and the therapeutic product is ELOVL lipid. fatty acid elongase 4 (ELOVL4); (13) The eye condition is associated with uveitis, and the therapeutic product is an anti-interleukin (AIL)-1, 6 (IL6) monoclonal antibody; (14) The eye condition is associated with uveitis and the therapeutic product is an anti-TNF alpha ( TNF-α monoclonal antibody; (15) The eye condition is associated with diabetic macular edema (DME), and the therapeutic product is an anti- an IL6 monoclonal antibody; (16) The eye condition is associated with red-green color blindness, and the therapeutic product is L-opsin (OPN1 LW); (17) The eye condition is associated with red-green color blindness, and the therapeutic product is a compound that inhibits M opsin (OPN1). MW); (18) The eye condition is associated with blue-cone monochromatism, and the therapeutic product is M opsin ( OPN1MW); (19) The eye pathology is associated with Leber congenital amaurosis-1 (LCA 1), and the therapeutic The product is guanylate cyclase 2D, retinal (GUCY2D); (20) The eye condition is associated with Leber congenital amaurosis type 2 (LCA 2), and the therapeutic The product is retinoid isomerohydrolase RPE65 (RPE65); (21) The eye condition is associated with LCA 3 and the therapeutic product is associated with spermatogenesis-related 7 (S PATA7); (22) The eye condition is associated with Leber congenital amaurosis-4 (LCA 4), and the therapeutic The product is aryl hydrocarbon receptor-interacting protein-like 1 (AIPL1); (23) The eye pathology is associated with Leber congenital amaurosis-5 (LCA 5), and the therapeutic The product is reversillin (LCA5); (24) The eye condition is associated with Leber congenital amaurosis-6 (LCA 6), and the therapeutic The product is RPGR-interacting protein 1 (RPGRIP1); (25) The eye condition is associated with Leber congenital amaurosis-7 (LCA 7), and the therapeutic The product is the cone-rod homeobox (CRX); (26) The eye condition is associated with Leber congenital amaurosis-8 (LCA 8), and the therapeutic The product is Crumbs cell polarity complex component 1 (CRB1); (27) The eye condition is associated with Leber congenital amaurosis-9 (LCA 9), and the therapeutic The product is nicotinamide nucleotide adenylyltransferase 1 (NMNAT1) is; (28) The eye condition is associated with Leber congenital amaurosis-10 (LCA 10), and the treatment The therapeutic product is centrosomal protein 290 (CEP290); (29) The eye condition is associated with Leber congenital amaurosis-11 (LCA 11), and the treatment The therapeutic product is inosine monophosphate dehydrogenase 1 (IMPDH1); (30) The eye condition is associated with Leber congenital amaurosis-12 (LCA 12), and the treatment 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 treatment The therapeutic product is retinol dehydrogenase 12 (RDH12); (32) The eye condition is associated with Leber congenital amaurosis-14 (LCA 14), and the treatment The therapeutic product is lecithin retinol acyltransferase (LRAT); (33) The eye condition is associated with Leber congenital amaurosis-15 (LCA 15), and the treatment The therapeutic product is tubby-like protein 1 (TULP1); (34) The eye condition is associated with Leber congenital amaurosis-16 (LCA 16), and the treatment The therapeutic product is a potassium voltage-gated channel subfamily J member 13 (KCNJ13 ) is; (35) The eye condition is associated with Leber's hereditary optic neuropathy (LHON), and the therapeutic product The enzyme is mitochondrially encoded NADH dehydrogenase 1 (MT-ND1). ru; (36) The eye condition is associated with LHON, and the therapeutic product acts on mitochondria. oxidized NADH dehydrogenase 4 (MT-ND4); (37) The eye condition is associated with LHON, and the therapeutic product acts on mitochondria. oxidized NADH dehydrogenase 6 (MT-ND6); (38) The eye condition is associated with neuromyelitis optica (NMO), and the therapeutic product is an anti-complement C5 monoclonal antibody; (39) The eye condition is associated with NMO, and the therapeutic product is an anti-IL6 monoclonal antibody. It is an antibody; (40) The eye condition is associated with uveitis, and the therapeutic product is an anti-complement C5 monoclonal antibody. is a monoclonal 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-1 0 (IL10); (43) The eye condition is associated with uveitis and the therapeutic product is an anti-TNF monoclonal antibody. is a clonal antibody; (44) The eye condition is associated with choroideremia, and the therapeutic product is Love Escort. Protein 1 (CHM); (45) The eye condition is associated with X-linked retinoschisis (XLRS) and the therapeutic product comprises: Retinoschisin (RS1); (46) The eye condition is associated with Bardet-Biedl syndrome 1, and the therapeutic product is Dee-Biedl syndrome 1 (BBS1); (47) The eye condition is associated with Bardet-Biedl syndrome 2, and the therapeutic product is Dee-Biedl syndrome 2 (BBS2); (48) The eye condition is associated with Bardet-Biedl syndrome 3, and the therapeutic product is for treating AD. P ribosylation factor-like GTPase 6 (ARL6); (49) The eye condition is associated with Bardet-Biedl syndrome 4, and the therapeutic product is Dee-Biedl syndrome 4 (BBS4); (50) The eye condition is associated with Bardet-Biedl syndrome 5 and the therapeutic product is Dee-Biedl syndrome 5 (BBS5); (51) The eye condition is associated with Bardet-Biedl syndrome 6 and the therapeutic product is Maki Muzik-Kaufman syndrome (MKKS); (52) The eye condition is associated with Bardet-Biedl syndrome 7, and the therapeutic product is Dee-Biedl syndrome 7 (BBS7); (53) The eye condition is associated with Bardet-Biedl syndrome 8, and the therapeutic product is tetracycline. Latricopeptide repeat domain 8 (TTC8); (54) The eye condition is associated with Bardet-Biedl syndrome 9, and the therapeutic product is Dee-Biedl syndrome 9 (BBS9); (55) The eye condition is associated with Bardet-Biedl syndrome and the therapeutic product is Rudy-Biedl syndrome 10 (BBS10); (56) The eye condition is associated with Bardet-Biedl syndrome 11, and the therapeutic product is partial motif containing 32 (TRIM32); (57) The eye condition is associated with Bardet-Biedl syndrome 12, and the therapeutic product is Rudy-Biedl syndrome 12 (BBS12); (58) The eye condition is associated with Bardet-Biedl syndrome 13 and the therapeutic product is KS transition zone complex subunit 1 (MKS1); (59) The eye condition is associated with Bardet-Biedl syndrome 14, and the therapeutic product is corpus cardiac protein 290 (CEP290); (60) The eye condition is associated with Bardet-Biedl syndrome 15 and the therapeutic product is D-repeat-containing planar cell polarity effector (WDPCP); (61) The eye condition is associated with Bardet-Biedl syndrome 16, and the therapeutic product is Serologically defined colon cancer antigen 8 (SDCCAG8); (62) The eye condition is associated with Bardet-Biedl syndrome 17, and the therapeutic product is isin zipper transcription factor-like 1 (LZTFL1); (63) The eye condition is associated with Bardet-Biedl syndrome 18, and the therapeutic product is B BSome interacting protein 1 (BBIP1); (64) The eye condition is associated with Bardet-Biedl syndrome 19 and the therapeutic product is intrahair transport 27 (IFT27); (65) The eye condition is associated with cone dystrophy, and the therapeutic product is a guanylic acid cyclase activating factor 1A (GUCA1A); (66) The eye condition is associated with optic nerve atrophy, and the therapeutic product inhibits OPA1 mitochondrion. rear dynamin-like GTPase (OPA1); (67) The eye condition is associated with retinitis pigmentosa 1, and the therapeutic product is a RP1 axoneme microenvironment. is tubule-associated (RP1); (68) The eye condition is associated with retinitis pigmentosa 2, and the therapeutic product is ARL3 G RP2 activator of TPase (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 a pre-mRNA. precursor processing factor 31 (PRPF31); (71) The eye condition is associated with retinitis pigmentosa 12 and the therapeutic product is Crumb s cell polarity complex component 1 (CRB1); (72) The eye condition is associated with retinitis pigmentosa 13, and the therapeutic product is a pre-mRNA. precursor processing factor 8 (PRPF8); (73) The eye condition is associated with retinitis pigmentosa 25 and the therapeutic product is an eye drop. homologue (EYS); (74) The eye condition is associated with retinitis pigmentosa 28 and the therapeutic product is FAM16 1 centrosomal protein A (FAM161A); (75) The eye condition is associated with retinitis pigmentosa 37, and the therapeutic product is a nuclear receptor stimulator. Nrf2 family 2 group E member 3 (NR2E3); (76) The eye condition is associated with retinitis pigmentosa 38, and the therapeutic product is a MER protein. oncogene, tyrosine kinase (MERTK); (77) The eye condition is associated with retinitis pigmentosa 40, and the therapeutic product is a phosphodiesterase inhibitor. PDE6B (Protein dehydrogenase 6B); (78) The eye condition is associated with retinitis pigmentosa 41 and the therapeutic product is prominence. 1 (PROM1); (79) The eye condition is associated with retinitis pigmentosa 43 and the therapeutic product is a phosphodiesterase inhibitor. sterase 6A (PDE6A); (80) The eye condition is associated with retinitis pigmentosa 56, and the therapeutic product is an interphotoreceptor matrix proteoglycan 2 (IMPG2); (81) The eye condition is associated with retinitis pigmentosa 62, and the therapeutic product is a therapeutic agent for treating male germ cells. cytoplasm-associated kinase (MAK); (82) The eye condition is associated with retinitis pigmentosa 80, and the therapeutic product is delivered via intraflagellar transport. 140 (IFT140); (83) The eye condition is associated with dry AMD, and the therapeutic product is an anti-complement C5 monoclonal antibody. It is a monoclonal antibody; (84) The eye condition is associated with dry AMD, and the therapeutic product is an anti-membrane attack complex ( MAC) monoclonal antibody; (85) The eye condition is associated with dry AMD, and the therapeutic product is an HtrA serine peptide. putidase 1 (HTRA1); (86) The eye condition is associated with Best's disease, and the therapeutic product is bestrophin 1 (B EST1); (87) The eye condition is associated with dry AMD, and the therapeutic product is a complement factor B anti-inflammatory drug. is a sense oligonucleotide; (88) The eye condition is associated with dry AMD, and the therapeutic product is an anti-beta-amylo It is a monoclonal antibody; (89) The eye condition is associated with dry AMD, and the therapeutic product is a compound comprising a CD59 glycoprotein. protein (CD59); (90) The eye condition is associated with dry AMD, and the therapeutic product is a channelrhodopsin inhibitor. ChR1; (91) The pathology of the eye is associated with dry AMD, and the therapeutic product is a channelrhodopsin inhibitor. Chlamydomonas reinhardtii It is a light-sensitive protein discovered in i; (92) The eye condition is associated with dry AMD, and the therapeutic product is an anti-complement factor C5a It is an aptamer; (93) The eye condition is associated with dry AMD, and the therapeutic product is an anti-complement factor D monoclonal antibody. It is a clonal antibody; (94) The eye pathology is associated with age-related retinal ganglion cell (RGC) degeneration, and the treatment The product is the DnaJ heat shock protein family (Hsp40) member C3 ( DNAJC3); (95) The eye condition is associated with blue-cone monochromatism (BCM), and the therapeutic product is opsin (OPN1LW); (96) The eye condition is associated with glaucoma, and the therapeutic product is beta-2 adrenaline. receptor siRNA; (97) The eye condition is associated with glaucoma, and the therapeutic product is a compound that inhibits caspase-2 (CAS P2); (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 a HIF-1 responsive protein. Protein RTP801 (RTP801); (100) The eye condition is associated with glaucoma, and the therapeutic product is a transforming growth factor beta 2 (TGFB2); (101) The eye condition is associated with glaucoma, and the therapeutic product is a brain-derived neurotrophic factor ( BDNF); (102) The eye condition is associated with glaucoma, and the therapeutic product is a ciliary neurotrophic factor ( CNTF); (103) The eye condition is associated with glaucoma, and the therapeutic product is a prostaglandin- endoperoxide synthase 2 (PTGS2); (104) The eye condition is associated with glaucoma, and the therapeutic product is prostaglandin F receptor (PTGFR); (105) The eye condition is associated with glaucoma, and the therapeutic product is hyaluronidase. ru; (106) The eye condition is associated with glaucoma, and the therapeutic product is a pigment epithelium-derived factor (P EDF); (107) The eye condition is associated with glaucoma, and the therapeutic product is a vascular endothelial growth factor (VGF). EGF); (108) The eye condition is associated with glaucoma, and the therapeutic product is placental growth factor (PGF ) is; (109) The eye condition is associated with glaucoma, and the therapeutic product is myocilin (MYOC). ) is; (110) The eye condition is associated with NMO and the therapeutic product is an anti-complement C5 monoclonal antibody. is a clonal antibody; (111) The eye condition is associated with NMO, and the therapeutic product is a C-C motif chemokine. CCR5 siRNA; (112) The eye condition is associated with NMO, and the therapeutic product is an anti-CD19 monoclonal antibody. is a clonal antibody; (113) The eye pathology is associated with retinitis pigmentosa associated with a rhodopsin mutation, and the therapeutic The therapeutic product is channelrhodopsin-1 (ChR1); (114) The eye pathology is associated with retinitis pigmentosa associated with a rhodopsin mutation, and the therapeutic The therapeutic product is channelrhodopsin-2 (ChR2); (115) The eye condition is associated with retinitis pigmentosa, and the therapeutic product is a ciliary nerve growth inhibitor. nutrient factor (CNTF); (116) The eye condition is associated with autosomal recessive retinitis pigmentosa, and the therapeutic product comprises: Crumbs cell polarity complex component 1 (CRB1); (117) The eye condition is associated with autosomal recessive retinitis pigmentosa, and the therapeutic product comprises: Crumbs cell polarity complex component 2 (CRB2); (118) The eye condition is associated with retinitis pigmentosa, and the therapeutic product is a histone deacetylase inhibitor. cetylase 4 (HDAC4); (119) The eye condition is associated with retinitis pigmentosa, and the therapeutic product is rhodopsin ( RHO); (120) The eye condition is associated with retinitis pigmentosa, and the therapeutic product is a nerve growth factor. (NGF); (121) The eye condition is associated with retinitis pigmentosa, and the therapeutic product is a nuclear factor, red blood cell sphere 2-like 2 (NRF2); (122) The eye condition is associated with retinitis pigmentosa, and the therapeutic product is a pigment epithelium-derived factor (PEDF); (123) The eye condition is associated with retinitis pigmentosa, and the therapeutic product is glutathione S-transferase PI1 (GSTP1); (124) The eye condition is associated with retinitis pigmentosa, and the therapeutic product is a rod-derived cone survival 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 retinaldehyde. hydrido-binding protein 1 (RLBP1); (127) The eye condition is associated with Stargardt's disease, and the therapeutic product is an anti-complement C5 It is an aptamer; (128) The eye condition is associated with uveitis, and the therapeutic product is a double homeobox. DUX4 (DUX4); (129) The eye condition is associated with uveitis, and the therapeutic product is a compound of the 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. Mon (ACTH); (132) The eye condition is associated with uveitis, and the therapeutic product inhibits caspase 1(C ASP1); (133) The eye condition is associated with uveitis, and the therapeutic product is an anti-CD59 monoclonal antibody. It is a monoclonal antibody; (134) The eye condition is associated with uveitis, and the therapeutic product is an anti-complement C5 aptamer. It is Ma; (135) The eye condition is associated with corneal neovascularization, and the therapeutic product is an insulin receptor inhibitor. Intracellular matrix 1 (IRS1); (136) The eye condition is associated with corneal neovascularization, and the therapeutic product is a NOTCH-regulated ankyrin repeat proteins (NRARPs); (137) The eye condition is associated with diabetic retinopathy, and the therapeutic product is a product that inhibits the NOTCH regulation. regulatory ankyrin repeat proteins (NRARPs); (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 activator. Gen (PLG); (140) The eye condition is associated with diabetic retinopathy and the therapeutic product is growth hormone. is; (141) The eye condition is associated with diabetic retinopathy and the therapeutic product is an insulin-like Growth factor 1 (IGF1); (142) The eye condition is associated with diabetic retinopathy, and the therapeutic product is an interleukin (IL)-1. kin 1 beta (IL1B); (143) The eye condition is associated with diabetic retinopathy and the therapeutic product is angiotensin II. Synthase I converting enzyme 2 (ACE2); (144) The eye condition is associated with diabetic retinopathy and the therapeutic product is IRS1. ru; (145) The eye condition is associated with diabetic retinopathy and the therapeutic product is an anti-integrin is an 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, and the therapeutic product is an anti-CD40 monoclonal antibody. monoclonal antibodies; (148) The eye condition is associated with Graves' ophthalmopathy, and the therapeutic product is an anti-insulin an IGF1R-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 an IGF-like growth factor 2 receptor (IGF2R) monoclonal antibody; (150) The eye condition is associated with DME and the therapeutic product is an anti-integrin oligonucleotide. is a peptide; (151) The eye condition is associated with DME and the therapeutic product is an anti-placental growth factor (PG) F) is a monoclonal antibody; (152) The eye condition is associated with DME and the therapeutic product is RTP801 siR It is NA; (153) The eye condition is associated with multiple sclerosis (MS)-related vision loss, and the therapeutic The product is ND1; (154) The eye condition is associated with myopia, and the therapeutic product is a matrix metalloproteinase. Methaminase 2 (MMP2) RNAi; (155) The eye condition is associated with X-linked recessive ocular albinism, and the therapeutic product is a G protein. Protein-coupled receptor 143 (GPR143); (156) The eye condition is associated with oculocutaneous albinism type 1, and the therapeutic product is tyrosine Ze (TYR); (157) The eye condition is associated with optic neuritis, and the therapeutic product inhibits caspase 2 (CA SP2); (158) The eye condition is associated with optic neuritis, and the therapeutic product is an anti-leucine-rich Peat and Ig domain-containing protein 1 (LINGO1) monoclonal antibody; or (159) The eye condition is associated with polypoidal choroidal vasculopathy, and the therapeutic product is an anti-coagulant. The method according to any one of claims 1 to 11 and 13 to 18, wherein the antibody is a C5 aptamer.

27. (1) the eye condition is associated with X-linked retinitis pigmentosa (XLRP), and the therapeutic product is a retinitis pigmentosa GTPase regulator (RPGR); (2) The eye condition is associated with color vision deficiency (ACHM) and the therapeutic product is a circular nucleic acid. Otide-gated channel beta 3 (CNGB3); (3) The eye condition is associated with color vision deficiency, and the therapeutic product is a cyclic nucleotide gate. Channel Alpha 3 (CNGA3); or (4) The eye condition is associated with biallelic RPE65 mutation-associated retinal dystrophy. and wherein the therapeutic product is retinoid isomerohydrolase RPE65 (RPE65). The method according to any one of claims 1 to 11 and 15 to 18,

28. (1) The ocular condition is associated with Batten-CLN1 and the therapeutic product is palmitoyl leu - protein thioesterase 1 (PPT1); (2) The ocular condition is associated with Batten-CLN2, and the therapeutic product is a tripeptide. leu-peptidase 1 (TPP1); (3) The ocular condition is associated with Batten-CLN3, and the therapeutic product is a battenin ( CLN3); (4) The ocular condition is associated with uveitis, and the therapeutic product is an anti-interleukin-6 (IL6) monoclonal antibody; (5) The ocular condition is associated with uveitis, and the therapeutic product is an anti-TNF alpha (TNF alpha) NF) is a monoclonal antibody; (6) The eye condition is associated with diabetic macular edema (DME) and the therapeutic product is an anti-I L6 monoclonal antibody; (7) The eye condition is associated with red-green color blindness, and the therapeutic product is a compound selected from the group consisting of L opsin (OPN1L) and L opsin (OPN1L). W); (8) The eye condition is associated with red-green color blindness, and the therapeutic product is M opsin (OPN1M W); (9) The eye condition is associated with blue-cone monochromatism, and the therapeutic product is M opsin (O PN1MW); (10) The eye condition is associated with Leber congenital amaurosis-1 (LCA 1), and the therapeutic The product is guanylate cyclase 2D, retinal (GUCY2D); (11) The eye condition is associated with Leber congenital amaurosis type 2 (LCA 2), and the therapeutic The product is retinoid isomerohydrolase RPE65 (RPE65); (12) The eye condition is associated with Leber congenital amaurosis-7 (LCA 7), and the therapeutic The product is the cone-rod homeobox (CRX); (13) The eye condition is associated with Leber congenital amaurosis-11 (LCA 11), and the treatment The therapeutic product is inosine monophosphate dehydrogenase 1 (IMPDH1); (14) The eye condition is associated with Leber congenital amaurosis-12 (LCA 12), and the treatment The therapeutic product is retinal degeneration 3, GUCY2D regulator (RD3); (15) The eye condition is associated with Leber congenital amaurosis-13 (LCA 13), and the treatment The therapeutic product is retinol dehydrogenase 12 (RDH12); (16) The eye condition is associated with Leber congenital amaurosis-15 (LCA 15), and the treatment The therapeutic product is tubby-like protein 1 (TULP1); (17) The eye condition is associated with Leber congenital amaurosis-16 (LCA 16), and the treatment The therapeutic product is a potassium voltage-gated channel subfamily J member 13 (KCNJ13 ) is; (18) The eye condition is associated with Leber's hereditary optic neuropathy (LHON), and the therapeutic product The enzyme is mitochondrially encoded NADH dehydrogenase 1 (MT-ND1). ru; (19) The eye condition is associated with LHON, and the therapeutic product acts on mitochondria. oxidized NADH dehydrogenase 4 (MT-ND4); (20) The eye condition is associated with LHON, and the therapeutic product acts on mitochondria. oxidized NADH dehydrogenase 6 (MT-ND6); (21) The eye condition is associated with neuromyelitis optica (NMO), and the therapeutic product is an anti-complement C5 monoclonal antibody; (22) The eye condition is associated with NMO, and the therapeutic product is an anti-IL6 monoclonal antibody. It is an antibody; (23) The eye condition is associated with uveitis, and the therapeutic product is an anti-complement C5 monoclonal antibody. is a monoclonal antibody; (24) The eye condition is associated with uveitis and the therapeutic product is angiotensin I converting enzyme (ACE); (25) The eye condition is associated with uveitis, and the therapeutic product is interleukin-1. 0 (IL10); (26) The eye condition is associated with uveitis and the therapeutic product is an anti-TNF monoclonal antibody. is a clonal antibody; (27) The eye condition is associated with X-linked retinoschisis (XLRS) and the therapeutic product comprises: Retinoschisin (RS1); (28) The eye condition is associated with Bardet-Biedl syndrome 1, and the therapeutic product is Dee-Biedl syndrome 1 (BBS1); (29) The eye condition is associated with Bardet-Biedl syndrome 3, and the therapeutic product is for treating AD. P ribosylation factor-like GTPase 6 (ARL6); (30) The eye condition is associated with Bardet-Biedl syndrome 5, and the therapeutic product is Dee-Biedl syndrome 5 (BBS5); (31) The eye condition is associated with Bardet-Biedl syndrome 6 and the therapeutic product is Maki Muzik-Kaufman syndrome (MKKS); (32) The eye condition is associated with Bardet-Biedl syndrome and the therapeutic product is Rudy-Biedl syndrome 10 (BBS10); (33) The eye condition is associated with Bardet-Biedl syndrome 11, and the therapeutic product is partial motif containing 32 (TRIM32); (34) The eye condition is associated with Bardet-Biedl syndrome 13 and the therapeutic product is KS transition zone complex subunit 1 (MKS1); (35) The eye condition is associated with Bardet-Biedl syndrome 18, and the therapeutic product is B BSome interacting protein 1 (BBIP1); (36) The eye condition is associated with Bardet-Biedl syndrome 19 and the therapeutic product is intrahair transport 27 (IFT27); (37) The eye condition is associated with cone dystrophy, and the therapeutic product is a guanylic acid cyclase activating factor 1A (GUCA1A); (38) The eye condition is associated with retinitis pigmentosa 13, and the therapeutic product is a pre-mRNA. precursor processing factor 8 (PRPF8); (39) The eye condition is associated with retinitis pigmentosa 37, and the therapeutic product is a nuclear receptor stimulator. is a member of the NR2 family 2 group E member 3 (NR2E3); or (40) The eye condition is associated with Best's disease, and the therapeutic product is bestrophin 1 (B EST1). The method according to any one of claims 1 to 11 and 13 to 18.

29. (1) The eye condition is related to biallelic RPE65 mutation-associated retinal dystrophy. and wherein the therapeutic product is a compound that inhibits retinoid isomerohydrolase RPE65 (RPE65). The method according to any one of claims 1 to 11 and 15 to 18.

30. (1) The ocular condition is associated with Batten-CLN2 and the therapeutic product is a tripeptide. di-peptidase 1 (TPP1); (2) The eye condition is associated with Usher syndrome type 1, and the therapeutic product is myosin V. IIA (MYO7A); (3) The eye condition is associated with Usher syndrome type 1, and the therapeutic product is a cadherin Related 23 (CDH23); (4) The eye condition is associated with Usher syndrome type 2, and the therapeutic product is a protococcid. herin-related 15 (PCDH15); (5) The eye condition is associated with Usher syndrome type 2, and the therapeutic product is phosphorus (USH2A); (6) The eye condition is associated with Usher syndrome type 3, and the therapeutic product is Curaline 1. (CLRN1); (7) The eye condition is associated with Stargardt's disease, and the therapeutic product is an ATP-binding cascade. ABCA4, a member of the ABCA subfamily A; (8) The eye condition is associated with Stargardt's disease, and the therapeutic product is ELOVL fat. acid elongase 4 (ELOVL4); (9) The eye condition is associated with red-green color blindness, and the therapeutic product is L opsin (OPN1L W); (10) The eye condition is associated with red-green color blindness, and the therapeutic product is a compound that inhibits M opsin (OPN1). MW); (11) The eye condition is associated with blue-cone monochromatism, and the therapeutic product is a compound that inhibits M opsin ( OPN1MW); (12) The eye condition is associated with Leber congenital amaurosis-1 (LCA 1), and the therapeutic The product is guanylate cyclase 2D, retinal (GUCY2D); (13) The eye condition is associated with Leber congenital amaurosis type 2 (LCA 2), and the therapeutic The product is retinoid isomerohydrolase RPE65 (RPE65); (14) The eye condition is associated with Leber congenital amaurosis-4 (LCA 4), and the therapeutic The product is aryl hydrocarbon receptor-interacting protein-like 1 (AIPL1); (15) The eye condition is associated with Leber congenital amaurosis-7 (LCA 7), and the therapeutic The product is the cone-rod homeobox (CRX); (16) The eye condition is associated with Leber congenital amaurosis-8 (LCA 8), and the therapeutic The product is Crumbs cell polarity complex component 1 (CRB1); (17) The eye condition is associated with Leber congenital amaurosis-9 (LCA 9), and the therapeutic The product is nicotinamide nucleotide adenylyltransferase 1 (NMNAT1) is; (18) The eye condition is associated with Leber congenital amaurosis-10 (LCA 10), and the treatment The therapeutic product is centrosomal protein 290 (CEP290); (19) The eye condition is associated with Leber congenital amaurosis-11 (LCA 11), and the treatment The therapeutic product is inosine monophosphate dehydrogenase 1 (IMPDH1); (20) The eye condition is associated with Leber congenital amaurosis-15 (LCA 15), and the treatment The therapeutic product is tubby-like protein 1 (TULP1); (21) The eye condition is associated with LHON, and the therapeutic product acts on mitochondria. oxidized NADH dehydrogenase 4 (MT-ND4); (22) The eye condition is associated with LHON, and the therapeutic product acts on mitochondria. oxidized NADH dehydrogenase 6 (MT-ND6); (23) The eye condition is associated with choroideremia, and the therapeutic product is Love Escort. Protein 1 (CHM); (24) The eye condition is associated with X-linked retinoschisis (XLRS), and the therapeutic product comprises: Retinoschisin (RS1); (25) The eye condition is associated with Bardet-Biedl syndrome 1, and the therapeutic product is Dee-Biedl syndrome 1 (BBS1); (26) The eye condition is associated with Bardet-Biedl syndrome 6 and the therapeutic product is Maki Muzik-Kaufman syndrome (MKKS); (27) The eye condition is associated with Bardet-Biedl syndrome and the therapeutic product is Rudy-Biedl syndrome 10 (BBS10); (28) The eye condition is associated with cone dystrophy, and the therapeutic product is a guanylic acid cyclase activating factor 1A (GUCA1A); (29) The eye condition is associated with optic nerve atrophy, and the therapeutic product inhibits OPA1 mitochondrion. rear dynamin-like GTPase (OPA1); (30) The eye condition is associated with retinitis pigmentosa 1, and the therapeutic product is a RP1 axoneme microenvironment. is tubule-associated (RP1); (31) The eye condition is associated with retinitis pigmentosa 2, and the therapeutic product is an ARL3 G RP2 activator of TPase (RP2); (32) The eye condition is associated with retinitis pigmentosa 7, and the therapeutic product is peripherin 2 (PRPH2); (33) The eye condition is associated with retinitis pigmentosa 11, and the therapeutic product is a pre-mRNA. precursor processing factor 31 (PRPF31); (34) The eye condition is associated with retinitis pigmentosa 13, and the therapeutic product is a pre-mRNA. precursor processing factor 8 (PRPF8); (35) The eye condition is associated with retinitis pigmentosa 37, and the therapeutic product is a nuclear receptor stimulator. Nrf2 family 2 group E member 3 (NR2E3); (36) The eye condition is associated with retinitis pigmentosa 38, and the therapeutic product is a MER protein. oncogene, tyrosine kinase (MERTK); (37) The eye condition is associated with retinitis pigmentosa 40, and the therapeutic product is a phosphodiesterase inhibitor. PDE6B (Protein dehydrogenase 6B); (38) The eye condition is associated with retinitis pigmentosa 41 and the therapeutic product is prominence. 1 (PROM1); (39) The eye condition is associated with retinitis pigmentosa 56, and the therapeutic product is an interphotoreceptor matrix proteoglycan 2 (IMPG2); (40) The eye condition is associated with retinitis pigmentosa 62, and the therapeutic product is a therapeutic agent for treating male germ cells. cytoplasm-associated kinase (MAK); (41) The eye condition is associated with retinitis pigmentosa 80, and the therapeutic product is delivered via intraflagellar transport. 140 (IFT140); or (42) The eye condition is associated with Best's disease, and the therapeutic product is bestrophin 1 (B EST1). The method according to any one of claims 1 to 11 and 13 to 18.

31. (1) the eye condition is associated with X-linked retinitis pigmentosa (XLRP), and the therapeutic product is a retinitis pigmentosa GTPase regulator (RPGR); (2) The eye condition is associated with color vision deficiency, and the therapeutic product is a cyclic nucleotide gate. channel beta 3 (CNGB3); or (3) The eye condition is associated with color vision deficiency, and the therapeutic product is a cyclic nucleotide gate. Any one of claims 1 to 11 and 15 to 18, which is channel alpha 3 (CNGA3). The method described in paragraph .

32. The recombinant viral vector encodes a promoter or an enhancer-promoter. and a nucleotide sequence encoding the promoter or enhancer-promoter. The nucleotide sequence encoding the therapeutic product is operably linked to a sequence, said promoter or enhancer-promoter comprising: (1) CAG promoter; (2) CBA promoter; (3) CMV promoter; (4) PR1.7 promoter; (5) rhodopsin kinase (GRK1) photoreceptor-specific enhancer-promoter; (6) hCARp promoter; (7) hRKp; (8) cone photoreceptor-specific human arrestin 3 (ARR3) promoter; (9) rhodopsin promoter; or (10) The method according to any one of claims 1 to 31, wherein the promoter is a U6 promoter.

33. The recombinant viral vector contains a nucleotide sequence encoding a cone-specific promoter. and a nucleotide sequence encoding said cone-specific promoter is provided in said gene. operably linked to said nucleotide sequence encoding a therapeutic product, (1) The eye condition is associated with red-green color blindness, and the therapeutic product is a compound that inhibits L-opsin (OPN1L). W); (2) The ocular condition is associated with red-green color blindness, and the therapeutic product is a compound selected from the group consisting of M opsin (OPN1M) and M opsin (OPN1M). W); (3) The ocular condition is associated with blue-cone monochromatism, and the therapeutic product is a compound that inhibits M-opsin (O PN1MW); (4) The eye condition is associated with cone dystrophy, and the therapeutic product is a guanylate synthase. is glucose activating factor 1A (GUCA1A); or (5) The eye condition is associated with blue-cone monochromatism (BCM), and the therapeutic product is The antibody according to any one of claims 1 to 11 and 13 to 15, which is psin (OPN1LW). method.

34. wherein the administering step delivers a therapeutically effective amount of the therapeutic product to the retina of the human subject. The method according to any one of claims 1 to 33.

35. wherein the therapeutically effective amount of the therapeutic product is produced by human retinal cells of the human subject.

35. The method of claim 34.

36. The therapeutically effective amount of the therapeutic product is administered to the human subject's human photoreceptor cells, horizontal cells, bilayer cells, and / or epithelial cells. to polar cells, amacrine cells, retinal ganglion cells, and / or retinal pigment epithelial cells of the outer limiting membrane The method of claim 34, wherein the protein is produced by

37. 37. The method of claim 36, wherein the human photoreceptor cells are cone and / or rod cells. method.

38. The retinal ganglion cells include midget cells, parasol cells, bilayered cells, giant retinal ganglion cells, and the like.

37. The method of claim 36, wherein the cells are cytoplasmic neurons, photosensitive ganglion cells, and / or Müller glia.

39. Any of claims 1 to 38, wherein the recombinant viral vector is an rAAV vector.

2. The method according to claim 1.

40. 40. The method of claim 39, wherein the recombinant viral vector is an rAAV8 vector. 。

41. After the administering step, an infrared thermal camera is used to measure the post-ocular injection thermal image of the substance injected into the eye.

41. The method of claim 1, further comprising monitoring the profile. method.

42. 42. The method of claim 41, wherein the infrared thermal camera is a FLIR T530 infrared thermal camera. How to do it.

43. The recombinant nucleotide expression vector is about 6.0 x 10 １０ Genome copies / eye dose The method of any one of claims 1 to 43, wherein the method is administered intravenously.

44. The recombinant nucleotide expression vector is about 1.6 x 10 １１ Genome copies / eye dose The method of any one of claims 1 to 43, wherein the method is administered intravenously.

45. The recombinant nucleotide expression vector is about 2.5×10 １１ Genome copies / eye dose The method of any one of claims 1 to 43, wherein the method is administered intravenously.

46. The recombinant nucleotide expression vector is about 5.0 x 10 １１ Genome copies / eye dose The method of any one of claims 1 to 43, wherein the method is administered intravenously.

47. The recombinant nucleotide expression vector is about 3.0 x 10 １２ Genome copies / eye dose The method of any one of claims 1 to 43, wherein the method is administered intravenously.

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