Aav-vectors for use in gene therapy of choroideremia

Abstract

The present invention relates to gene therapy for treatment or prevention of choroideremia.

1 . A vector, which comprises an adeno-associated virus (AAV) genome or a derivative thereof and a polynucleotide sequence encoding REP1 or a variant thereof. 
     
     
         2 . The vector according to  claim 1 , wherein said derivative is a chimeric, shuffled or capsid modified derivative. 
     
     
         3 . The vector according to  claim 1 , wherein said AAV genome is from a naturally derived serotype or isolate or clade of AAV. 
     
     
         4 . The vector according to  claim 3 , wherein said serotype is AAV serotype 2 (AAV2). 
     
     
         5 . The vector according to  claim 4 , which comprises SEQ ID NO: 1 or a derivative thereof. 
     
     
         6 . The vector according to  claim 1 , wherein said polynucleotide sequence encodes a polypeptide having at least 70% homology to SEQ ID NO: 3 over its entire sequence. 
     
     
         7 . The vector according to  claim 6 , wherein said polynucleotide sequence has at least 70% homology to SEQ ID NO: 2 over its entire sequence. 
     
     
         8 . The vector according to  claim 1 , which comprises a promoter sequence operably linked to said polynucleotide sequence encoding REP1 or a variant thereof. 
     
     
         9 . The vector according to  claim 8 , wherein said promoter is constitutively active. 
     
     
         10 . The vector according to  claim 8 , wherein expression from said promoter is retinal-cell specific. 
     
     
         11 . The vector according to  claim 1 , which comprises one or more additional regulatory sequences. 
     
     
         12 . The vector according to  claim 11 , which comprises a sequence having at least 70% homology to SEQ ID NO: 5 over its entire sequence. 
     
     
         13 . A method of treating or preventing choroideremia in a patient in need thereof, comprising administering a therapeutically effective amount of a vector according to  claim 1  to said patient by direct retinal, subretinal or intravitreal injection, and thereby treating or preventing choroideremia in said patient. 
     
     
         14 . The method according to  claim 13 , wherein said vector is administered directly into the subretinal space. 
     
     
         15 . (canceled)