Synthetic combinatorial aav capsid library for targeted gene therapy

Abstract

Disclosed are compositions and methods for producing modified adeno-associated virus (AAV) cap genes and combinatorial libraries of chimeric AAV vectors and virions; selecting for virions displaying cell-specific tropisms; and, in certain embodiments, producing helper vectors containing one or more modified AAV cap genes. The synthetic combinatorial AAV capsid libraries of the invention are useful in introducing into selected target host cells one or more nucleic acid molecules. The viral vectors and genetic constructs disclosed herein are also useful in a variety of diagnostic and/or therapeutic gene-therapy regimens.

1 .- 28 . (canceled) 
     
     
         29 . A non-naturally occurring nucleic acid comprising:
 (a) a first nucleotide sequence encoding at least one AAV Rep protein from serotype 2;   (b) a second nucleotide sequence encoding at least one AAV Cap protein which differs from wildtype serotype 2 at least at one nucleotide position; and   (c) a first AAV terminal repeat from serotype 2 and a second AAV terminal repeat from serotype 2,   
       wherein the first and second nucleotide sequences are interposed between the first and the second AAV terminal repeats.