ADENOASSOCIATED VIRUS AS A VECTOR FOR LIVER-DIRECTED GENE-THERAPY

Factors relevant to the successful application of adeno-associated vir us (AAV) vectors for liver-directed gene therapy were evaluated. Vecto rs with different promoters driving expression of human alpha-1-antitr ypsin (alpha-1AT) were injected into the portal circulation of immunod eficient mice. a-1AT expression was stable but dependent on the promot er. Southern analysis of liver DNA revealed approximately 0.1 to 2.0 p rovirus copies/diploid genome in presumed head-to-tail concatamers. In situ hybridization and immunohistochemical analysis revealed expressi on in approximately 5% of hepatocytes clustered in the pericentral reg ion. These results support the use of AAV as a vector for diseases tre atable by targeting of hepatocytes.