AAV4 Vector And Uses Thereof

These patent applications describe the cloning and characterization of the full-length genome of adeno-associated virus type 4 (AAV4). AAV4, like other members of the AAV family, may be useful as a vector for gene therapy.

When compared to AAV2, AAV4 may be better suited as a vector due to its larger size -- which permits efficient encapsidation of a larger recombinant genome -- and its greater buoyant density -- which allows for easier separation of AAV4 from contaminating helper virus. Other characteristics of AAV4 which distinguish it from AAV2 and AAV3 are its expanded promoter region, its distinct capsid protein, its different tissue tropism and its ability to bind hemagluttinin (HA). While AAV4 has several distinguishing characteristics from AAV2 and AAV3 it also shares significant homology, greater than 90%, with the Rep proteins of AAV2 and AAV3.

Studies using a lacZ reporter gene suggest that AAV4 can transduce human, monkey, and rat cells. Other studies comparing transduction efficiencies in a number of cell lines, competition cotransduction experiments and the effect of trypsin on transduction efficiency suggest that the cellular receptor for AAV4 is distinct from that of AAV2.