ADENOASSOCIATED VIRUS 2-MEDIATED GENE-TRANSFER IN-VIVO - ORGAN-TROPISM AND EXPRESSION OF TRANSDUCED SEQUENCES IN MICE

Adeno-associated virus 2 (AAV), a non-pathogenic human parvovirus, is gaining attention as a vector for its potential use in human gene ther apy. However, few studies have examined the safety and the efficacy of this vector system in vivo. We report here that recombinant AAV vecto rs, when directly injected intravenously in mice, accumulated predomin antly in liver cells, suggesting that AAV may possess in vivo organ-tr opism for liver. The transduced lacZ reporter gene was expressed in he patocytes in the liver and, at the level examined, did not appear to i nduce any detectable cytotoxic T lymphocyte response against beta Gal. AAV-mediated transduction of murine hematopoietic progenitor cells ex vivo followed by transplantation into lethally irradiated syngeneic m ice also revealed high-efficiency gene transfer into progeny cells wit hout any observable cytotoxicity or deleterious effect. The transduced reporter gene sequences were also expressed in mice in vivo. The AAV- based vectors may thus prove useful as a potentially safe alternative to the more commonly used retrovirus- and adenovirus-based vector syst ems.