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 treating an ocular disorder characterized by a defect or absence of a normal gene in ocular cells of a human subject, the method comprising the step of
 administering to said subject by subretinal injection a recombinant adeno-associated virus (rAAV) comprising a nucleic acid sequence encoding a normal gene under the control of a promoter sequence which expresses the product of the gene in ocular cells, wherein expression of the normal gene provides to the cells the product necessary to restore or improve visual function in said subject, wherein said normal gene is the LCA5 or RP12 gene.   
     
     
         2 . 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 t 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, formulated with a carrier and additional components suitable for subretinal injection,. wherein said normal gene is the LCA5 or RP12 gene 
     
     
         3 . The method according to  claim 1 , wherein the ocular disorder is Leber congenital amaurosis (LCA) and said normal gene is LCA5. 
     
     
         4 . The method according to  claim 3 , wherein said LCA is caused by a mutation in the normal LCA5 gene. 
     
     
         5 . The method according to  claim 1 , wherein the ocular disorder is retinitis pigmentosa (RP) and said normal gene is the RP12 gene. 
     
     
         6 . The method according to  claim 5 , wherein the RP is caused by a mutation in the RP12 gene. 
     
     
         7 . The method according to  claim 1 , wherein said ocular cells are selected from the group consisting of RPE cells and photoreceptor cells. 
     
     
         8 . The method according to  claim 1 , wherein said promoter is cell-specific or comprises a chicken beta actin promoter/CMV enhancer. 
     
     
         6 . The method according to  claim 1 , wherein said normal gene is obtained from the same subject species as the subject being treated. 
     
     
         7 . The method according to  claim 1 , wherein said rAAV vector is administered in a physiologically acceptable vehicle. 
     
     
         8 . The method according to  claim 7 , wherein said vehicle comprises one or more of a buffer and a surfactant. 
     
     
         9 . The method according to  claim 1 , wherein said normal gene is obtained from the same subject species as the subject being treated. 
     
     
         10 . The composition according to  claim 2 , wherein the ocular disorder is Leber congenital amaurosis (LCA) and said normal gene is LCA5. 
     
     
         11 . The composition according to  claim 10 , wherein said LCA is caused by a mutation in the normal LCA5 gene. 
     
     
         12 . The composition according to  claim 2 , wherein the ocular disorder is retinitis pigmentosa (RP) and said normal gene is the RP12 gene. 
     
     
         13 . The composition according to  claim 12 , wherein the RP is caused by a mutation in the RP12 gene. 
     
     
         14 . The composition according to  claim 2 , wherein said ocular cells are selected from the group consisting of RPE cells and photoreceptor cells. 
     
     
         15 . The composition according to  claim 2 , wherein said promoter is cell-specific or comprises a chicken beta actin promoter/CMV enhancer. 
     
     
         16 . The composition according to  claim 2 , wherein said normal gene is obtained from the same subject species as the subject being treated. 
     
     
         17 . The composition according to  claim 2 , wherein said rAAV vector is administered in a physiologically acceptable vehicle. 
     
     
         18 . The composition according to  claim 17 , wherein said vehicle comprises one or more of a buffer and a surfactant. 
     
     
         19 . The composition according to  claim 2 , wherein said normal gene is obtained from the same subject species as the subject being treated.