ADENOVIRUS-MEDIATED UROKINASE GENE-TRANSFER INDUCES LIVER-REGENERATION AND ALLOWS FOR EFFICIENT RETROVIRUS TRANSDUCTION OF HEPATOCYTES IN-VIVO

Retrovirus-mediated gene transfer into hepatocytes in vivo results in long-term gene expression. Limitations include the need to remove two- thirds of the liver and the relatively low frequency of gene transfer, To increase gene transfer without surgical hepatectomy, mouse hepatoc ytes were transduced in vivo with a recombinant adenovirus that transi ently expressed urokinase, resulting in high rates of asynchronous liv er regeneration. During the regenerative phase, in vivo retroviral-med iated gene transfer in hepatocytes resulted in 5- to 10-fold greater t ransduction efficiencies than that obtained by conventional partial he patectomy. In 3-4 weeks, the architecture and microscopic structure of the recipient livers were normal, The two-viral system of achieving p ermanent transgene expression from hepatocytes in vivo offers an alter native approach to current ex vivo and in vivo gene-transfer models.