Our laboratory focuses on the development and application of adeno-associated virus (AAV) as delivery vector for gene therapy. We have manipulated the virus replication cycle so that the viral genome forms a double-stranded DNA molecule instead of the natural single-stranded DNA genome. This bypasses the inefficient step of waiting for the recipient cell to synthesize a complementary DNA strand. We are using these "self-complementary" AAV vectors to deliver genes in therapies where rapid and efficient gene expression is at a premium. One such application is the delivery of antioxidant genes to liver to prevent oxidative damage in a transplantation model. Other projects in our laboratory involve the delivery of short interfering RNA (siRNA) to shut down the expression of targeted genes. This will allow the rapid assessment of gene function in vivo. We are also addressing the safety of AAV gene therapy in terms of the potential risk of cancer due to insertion of the vector genome into recipient cell chromosomes. This work involves the characterization of interactions between the AAV vector genome and the cellular DNA repair system, as well as long term tumor studies in mice.

Hacker UT, Wingenfeld L, Kofler DM, Schuhmann NK, Lutz S, Herold T, King SB, Gerner FM, Perabo L, Rabinowitz J, McCarty DM, Samulski RJ, Hallek M, Buning H.   Adeno-associated virus serotypes 1 to 5 mediated tumor cell directed gene transfer and improvement of transduction efficiency. J Gene Med. 2005 Nov; 7 (11): 1429-38

Choi VW, Samulski RJ, McCarty DM.   Effects of adeno-associated virus DNA hairpin structure on recombination. J Virol. 2005 June; 79 (11): 6801-7