DEVELOPMENT OF NOVEL CELL-SURFACE CD34-TARGETED RECOMBINANT ADENOASSOCIATED VIRUS VECTORS FOR GENE-THERAPY

Recombinant adenoassociated virus (rAAV) type 2 vectors have been used to transduce a wide variety of cell types, including hematopoietic pr ogenitor cells, For in vivo gene transfer, it is desirable to have an rAAV vector that specifically transduces selected target cells, As a f irst step toward generating an rAAV vector capable of targeting delive ry in vivo, we have engineered a chimeric protein combining the AAV ca psid protein and the variable region of a single-chain antibody agains t human CD34 molecules, a cell surface marker for hematopoietic stem/p rogenitor cells. Inclusion of the chimeric CD34 single-chain antibody- AAV capsid proteins within an rAAV virion significantly increased the preferential infectivity of rAAV for the CD34(+) human myoleukemia cel l line KG-1, which is normally refractory to rAAV transduction, Antibo dies against the single-chain antibody and the CD34 protein blocked th is transduction, This chimeric vector represents a significant improve ment in the host range of rAAV and the first step toward specific gene delivery by rAAV vectors to cells of choice, in this case, hematopoie tic progenitor cells, for the treatment of human disease.