Treatment of retinal degeneration using gene therapy

Abstract

The present invention relates to an improved method of providing photoreceptor function to a cell, for example for use in the treatment of retinal degeneration. The present invention also relates to compositions and kits, in particular for use in such methods.

1 - 81 . (canceled) 
     
     
         82 - 90 . (canceled) 
     
     
         91 . A composition comprising a nucleic acid vector comprising a nucleic acid sequence encoding a human rhodopsin or a human photopsin, wherein the nucleic acid is under control of a promoter which directs expression of said nucleic acid to an inner retinal cell in a subject with a condition. 
     
     
         92 . A composition according to  claim 91 , wherein the composition is an injectable liquid. 
     
     
         93 . The composition of  claim 91 , further comprising an extracellular matrix degradation enzyme or an active fragment thereof. 
     
     
         94 . The composition of  claim 93 , comprising a first injectable liquid comprising the nucleic acid sequence encoding human rhodopsin or human photopsin; and ii) a second injectable liquid comprising the extracellular matrix degradation enzyme. 
     
     
         95 . The composition of  claim 94 , wherein the first injectable liquid is administered to the subject prior to an administration of the second injectable liquid. 
     
     
         96 . The composition of  claim 94 , wherein the first injectable liquid is administered to the subject subsequent to an administration of the second injectable liquid. 
     
     
         97 . The composition of  claim 94 , wherein the first injectable liquid is administered to the subject simultaneously with an administration of the second injectable liquid. 
     
     
         98 . The composition of  claim 93  wherein the extracellular matrix degradation enzyme is capable of degrading a glycosaminoglycan. 
     
     
         99 . The composition of  claim 93 , wherein the extracellular matrix degradation enzyme or an active fragment thereof is selected from the group consisting of a collagenase, hyaluronan lyase, heparinase I, heparinase II, heparinase III, chondroitin ABC lyase, chondroitin AC lyase, a metalloproteinase, an ADAMTS, a plasmin (serine protease plasmin or its truncated form microplasmin (Ocriplasmin)), neutrophil elastase and cathepsin G, neuraminidase, N-glycanase, O-glycanase, and pronase. 
     
     
         100 . The composition of  claim 93 , wherein the extracellular matrix degradation enzyme or an active fragment thereof comprises a combination of two or more extracellular matrix degradation enzymes. 
     
     
         101 . The composition of  claim 100 , wherein the extracellular matrix degradation enzyme or an active fragment thereof comprises a combination of hyaluronan lyase and heparinase III. 
     
     
         102 . The composition of  claim 93  wherein an active fragment shares at least 70% sequence identity with a native extracellular matrix degradation enzyme. 
     
     
         103 . The composition of  claim 91 , wherein the vector is a viral vector. 
     
     
         104 . The composition of  claim 103 , wherein the viral vector is an AAV vector. 
     
     
         105 . The composition of  claim 104 , wherein the AAV vector comprises an AAV serotype 2 vector. 
     
     
         106 . The composition of  claim 105 , wherein the AAV vector comprises an AAV 4YF vector. 
     
     
         107 . The composition of  claim 105 , wherein the AAV serotype 2 vector comprises an AAV 7m8 vector. 
     
     
         108 . The composition of  claim 91 , wherein the promoter is selected from the group consisting of L7, thy-1, recoverin, calbindin, human CMV, GAD-67, chicken beta-actin, Grm6, Grm6 enhancer-SV40 fusion protein. 
     
     
         109 . The composition of  claim 108 , wherein the promoter comprises a Grm6 enhancer-SV40 fusion protein. 
     
     
         110 . The composition of  claim 91 , wherein the inner retinal cell is a rod cell, a cone cell, an ON-bipolar cell, an OFF-bipolar cell, a horizontal cell, a ganglion cell, or an amacrine cell. 
     
     
         111 . The composition of  claim 91 , wherein the condition is a retinal dystrophy including a rod dystrophy, a rod-cone dystrophy, a cone-rod dystrophy, a cone dystrophy and a macular dystrophy; another form of retinal or macular degeneration, an ischemic condition, uveitis, edema, or any other disease resulting from loss of photoreceptor ability. 
     
     
         112 . The composition of  claim 91 , wherein the human photopsin is selected from the group consisting of Long Wavelength Sensitive (OPN1LW) Opsin, Middle Wavelength Sensitive (OPN1MW), and Short Wavelength Sensitive (OPN1SW) Opsin. 
     
     
         113 . The composition according to  claim 91 , wherein the nucleic acid sequence comprises I) the rhodopsin (RHO) gene, or a fragment or derivative thereof, or ii) the Cone  Homo sapiens  opsin 1, long wave sensitive OPN1LW gene, or a fragment or derivative thereof; or iii) the Cone  Homo sapiens  opsin 1: medium-wave sensitive OPN1MW, or a fragment or deriva-tive thereof; or iv) the Cone  Homo sapiens  opsin 1, short-wave-sensitive (OPN1 SW), or a fragment or derivative thereof. 
     
     
         114 . The composition according to  claim 91  wherein the nucleic acid sequence encoding human rhodopsin comprises the sequence of Genbank Accession No. BC111451.3 or a fragment or derivative thereof, or a sequence having at least 70% sequence identity thereto. 
     
     
         115 . A vector according to  claim 91  wherein the vector further comprises one or more regulatory sequences which direct expression to an inner retinal cell. 
     
     
         116 . A composition according to  claim 93  wherein the first and second injectable liquids are provided in separate containers.