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.

What is claimed is: 
     
         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.