Adenovirus-mediated Gene Transfer: Strategies and Applications in Lipoprotein Research

Adenovirus-mediated gene transfer into mammalian liver is a highly efficient process that can result in transduction frequencies approaching 100%. Coupled with efficient expression levels from these vectors, the transfer of genes encoding a variety of enzymes, ligands and receptors has resulted in physiologically significant effects on lipoprotein metabolism. Adenovirus vectors have not only proved useful in the study of lipoprotein metabolism, they may also ultimately be used for hepatic gene therapy of inherited monogenic and polygenic disorders. The main hurdle to overcome before this technology can be therapeutically applied is the relatively short duration of expression in immunocompetent hosts. Apparently, cytolytic T-lymphocyte-mediated rejection of the transduced hepatocytes is caused by low-level expression of adenovirus genes. Several strategies have been recently employed in an attempt to circumvent this immune response and prolong transgene expression.