Method of treating or retarding the development of blindness

Abstract

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.