Widespread gene delivery to motor neurons using peripheral injection of aav vectors

Abstract

The present invention relates to compositions and methods, in particular to methods based on systemic injection of rAAV, for delivering genes to cells of the central nervous system in mammals, such as brain neurons or glial cells, and in particular to motor neurons or glial cells of the spinal cord The invention also relates to methods of treating motor neuron disorders in mammals by expression of therapeutic genes. The invention stems from the unexpected discovery that peripheral injection of AAV vectors leads to a bypass of the blood brain barrier and a massive infection of motor neurons. The invention may be used in any mammal, including human subjects.

1 - 12 . (canceled) 
     
     
         13 . A double-stranded self-complementary adeno-associated virus vector (scAAV vector) comprising an AAV9-derived capsid and a genome comprising a nucleic acid sequence encoding a survival of motor neuron (SMN) protein. 
     
     
         14 . The scAAV vector according to  claim 13 , wherein the nucleic acid sequence is operably linked to a promoter which is specific or functional in motor neurons. 
     
     
         15 . The scAAV vector according to  claim 13 , which is a pseudotyped vector. 
     
     
         16 . The scAAV vector according to  claim 14 , which is a pseudotyped vector. 
     
     
         17 . The scAAV vector according to  claim 15 , comprising an AAV2-derived genome. 
     
     
         18 . The scAAV vector according to  claim 16 , comprising an AAV2-derived genome. 
     
     
         19 . The scAAV vector according to  claim 13 , comprising a replication defective AAV genome lacking functional Rep and Cap encoding viral sequences. 
     
     
         20 . An scAAV vector comprising an AAV9-derived capsid and a replication defective AAV2-derived genome lacking functional Rep and Cap encoding viral sequences,
 wherein said genome comprises a nucleic acid sequence encoding a survival of motor neuron (SMN) protein, and   wherein the nucleic acid sequence is operably linked to a promoter which is specific or functional in motor neurons.