METHOD OF TREATING OR RETARDING THE DEVELOPMENT OF BLINDNESS
A method for treating an ocular disorder characterized by the defect or absence of a normal gene in the ocular cells of a human or animal subject involves administering to the subject by subretinal injection an effective amount of a recombinant adeno-associated virus carrying a nucleic acid sequence encoding the normal gene under the control of a promoter sequence which expresses the product of the gene in the ocular cells. The ocular cells are preferably retinal pigment epithelial (RPE) cells, and the gene is preferably an RPE-specific gene, e.g., RPE65. The promoter is one that can express the gene product in the RPE cells. Compositions for subretinal administration are useful in this method.
1 . A composition for treatment of an ocular disorder characterized by a defect or absence of a normal gene in ocular cells of a subject, said composition comprising an effective amount of a recombinant adeno-associated virus (rAAV) carrying a nucleic acid sequence encoding said normal gene under the control of a promoter sequence which expresses the product of said normal gene in said ocular cells.
2 . The composition according to claim 1 , wherein said normal gene is a retinal pigment epithelium-specific gene.
3 . The composition according to claim 3 , wherein said normal gene is retinal pigment specific epithelial 65 (RPE65).
4 . The composition according to claim 1 formulated with a carrier and additional components suitable for subretinal injection.
5 . A composition for restoring visual function in a subject having an ocular disorder caused by a defect or absence of a normal retinal pigment specific epithelial 65 (RPE65) in ocular cells of said subject, said composition comprising an effective amount of a recombinant adeno-associated virus (rAAV) carrying a nucleic acid sequence encoding said RPE65 gene under the control of a promoter sequence which expresses the product of said RPE65 gene in said ocular cells.
6 . The composition according to claim 5 , wherein said RPE65 gene is operably linked to a chicken beta actin promoter/CMV enhancer.
7 . The composition according to claim 5 , wherein said ocular disorder is retinitis pigmentosa, cone-rod dystrophy, or retinal degeneration.
8 . The composition according to claim 5 , wherein said RPE65 gene is obtained from the same subject species as the subject being treated.
9 . A method for restoring visual function in a subject having an ocular disorder caused by a defect or absence of a normal retinal pigment specific epithelial 65 (RPE65) gene in ocular cells, the method comprising:
administering to the subject by subretinal injection a recombinant adeno-associated virus (rAAV) comprising a nucleic acid sequence encoding a normal retinal pigment specific epithelial 65 (RPE65) gene operably linked to a chicken beta actin promoter/CMV enhancer, wherein said rAAV is administered in a dosage of from 1×10 9 to 2×10 12 rAAV in a volume comprising about 150 microliters, thereby restoring visual function in said subject.
10 . The method according to claim 9 , wherein said ocular disorder is retinitis pigmentosa or cone-rod dystrophy or retinal degeneration.
11 . The method according to claim 9 , wherein said normal RPE65 gene is obtained from the same subject species as the subject being treated.
12 . The method according to claim 9 , wherein said subject is a human.
13 . The method according to claim 9 , wherein said rAAV is administered in a volume comprising about 250 microliters.
14 . The method according to claim 9 , wherein said rAAV is administered in a volume of between 150 to 800 microliters.
15 . The method according to claim 9 , wherein said rAAV is administered in a volume comprising of between 250 to 500 microliters.
16 . The method according to claim 9 , wherein said rAAV is administered in a volume comprising about 500 microliters.
17 . The method according to claim 9 , wherein said rAAV is administered in a volume comprising about 800 microliters.
18 . The method according to claim 9 , wherein said rAAV is administered in a dosage of from 1×10 10 to 2×10 11 rAAV in a volume of between 250 to 500 microliters.
19 . The method according to claim 9 , wherein said ocular cells are retinal pigment epithelial cells.
20 . The method according to claim 9 , wherein said ocular cells are photoreceptor cells.