Cns targeting aav vectors and methods of use thereof

Abstract

The invention in some aspects relates to recombinant adeno-associated viruses useful for targeting transgenes to CNS tissue, and compositions comprising the same, and methods of use thereof. In some aspects, the invention provides methods and compositions for treating CNS-related disorders.

1 - 55 . (canceled) 
     
     
         56 . A method for delivering a transgene to CNS tissue in a subject, the method comprising: administering an effective amount of a recombinant adeno-associated virus (rAAV) by intracerebral injection into the putamen of the subject, wherein the rAAV comprises (i) an AAV capsid protein, and (ii) a nucleic acid comprising a transgene, wherein the transgene encodes glial-derived growth factor (GDNF). 
     
     
         57 . The method of  claim 56 , wherein the AAV capsid protein is an AAV2 capsid protein. 
     
     
         58 . The method of  claim 57 , wherein the intracerebral injection includes the use of a stereotactic device to guide the injection. 
     
     
         59 . The method of  claim 57 , wherein the method comprises administering a pharmaceutical composition comprising a pharmaceutically acceptable carrier and an effective amount of the rAAV. 
     
     
         60 . The method of  claim 59 , wherein between 100 μl to 1 ml of the pharmaceutical composition is injected into the putamen of the subject. 
     
     
         61 . The method of  claim 60 , wherein the effective amount of the rAAV for intracerebral injection to the subject is in a range of 1×10 10  genome copies to 1×10 11  genome copies. 
     
     
         62 . The method of  claim 60 , wherein the effective amount of the rAAV for intracerebral injection to the subject is in a range of 1×10 11  genome copies to 1×10 12  genome copies. 
     
     
         63 . The method of  claim 60 , wherein the effective amount of the rAAV for intracerebral injection to the subject is in a range of 1×10 12  genome copies to 1×10 13  genome copies. 
     
     
         64 . The method of  claim 60 , wherein the effective amount of the rAAV for intracerebral injection to the subject is in a range of 1×10 13  genome copies to 1×10 14  genome copies. 
     
     
         65 . A method for treating Parkinson's Disease in a subject, the method comprising: administering an effective amount of a recombinant adeno-associated virus (rAAV) by intracerebral injection into the putamen of the subject, wherein the rAAV comprises (i) an AAV capsid protein, and (ii) a nucleic acid comprising a transgene, wherein the transgene encodes glial-derived growth factor (GDNF). 
     
     
         66 . The method of  claim 65 , wherein the AAV capsid protein is an AAV2 capsid protein. 
     
     
         67 . The method of  claim 66 , wherein the intracerebral injection includes the use of a stereotactic device to guide the injection. 
     
     
         68 . The method of  claim 66 , wherein the method comprises administering a pharmaceutical composition comprising a pharmaceutically acceptable carrier and an effective amount of the rAAV. 
     
     
         69 . The method of  claim 68 , wherein between 100 μl to 1 ml of the pharmaceutical composition is injected into the putamen of the subject. 
     
     
         70 . The method of  claim 69 , wherein the effective amount of the rAAV for intracerebral injection to the subject is in a range of 1×10 10  genome copies to 1×10 11  genome copies. 
     
     
         71 . The method of  claim 69 , wherein the effective amount of the rAAV for intracerebral injection to the subject is in a range of 1×10 11  genome copies to 1×10 12  genome copies. 
     
     
         72 . The method of  claim 69 , wherein the effective amount of the rAAV for intracerebral injection to the subject is in a range of 1×10 12  genome copies to 1×10 13  genome copies. 
     
     
         73 . The method of  claim 69 , wherein the effective amount of the rAAV for intracerebral injection to the subject is in a range of 1×10 13  genome copies to 1×10 14  genome copies.