ASSESSMENT OF RECOMBINANT ADENOVIRAL VECTORS FOR HEPATIC GENE-THERAPY

Recombinant adenoviral vectors have recently been used to transfer gen es into a number of different cell types in vitro and in vivo. A recom binant adenoviral vector bearing the Escherichia coli beta-galactosida se (beta-gal) gene was used to quantitate the frequency of hepatocyte transduction in the mouse after direct viral infusion into the portal vein. When 10(10) adenoviral particles were infused, over 95% of the h epatocytes were transduced in vivo as determined by x-gal staining. Th e transduction protocol is relatively safe in that there is no detecta ble helper virus production in transduced animals and that very few ex trahepatic cells are transduced by this method. There is also no evide nce of significant liver pathology unless substantially greater quanti ties of virus are used. However, the transduced hepatocytes do not app ear to persist in vivo because the percentage of hepatocytes expressin g beta-gal declined over time. Four months after the procedure, 0.5-10 % of the hepatocytes contain detectable beta-gal activity in vivo. The change in beta-gal-positive cells correlates with decreasing amounts of adenoviral DNA. Thus, current recombinant adenoviral vectors may ha ve clinical applications in gene therapy for acute hepatic disorders.