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 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.
2 . The method according to claim 1 , wherein said ocular disorder is retinitis pigmentosa or cone-rod dystrophy or retinal degeneration.
3 . The method according to claim 1 , wherein said normal RPE65 gene is obtained from the same subject species as the subject being treated.
5 . The method according to claim 1 , wherein said subject is a human.
6 . The method according to claim 1 , wherein said rAAV is administered in a volume comprising about 250 microliters.
7 . The method according to claim 1 , wherein said rAAV is administered in a volume of between 150 to 800 microliters.
8 . The method according to claim 1 , wherein said rAAV is administered in a volume comprising of between 250 to 500 microliters.
9 . The method according to claim 1 , wherein said rAAV is administered in a volume comprising about 500 microliters.
10 . The method according to claim 1 , wherein said rAAV is administered in a volume comprising about 800 microliters.
11 . The method according to claim 1 , 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.
12 . The method according to claim 1 , wherein said ocular cells are retinal pigment epithelial cells.
13 . The method according to claim 1 , wherein said ocular cells are photoreceptor cells.