Adenovirus−mediated in vivo gene transfer and expression in normal rat liver

Replication deficient, recombinant adenovirus (Ad) vectors do not require target cell replication for transfer and expression of exogenous genes and thus may be useful for in vivo gene therapy in hepatocytes. In vitro, primary cultures of rat hepatocytes infected with a recombinant Ad containing a human 1−antitrypsin cDNA (Ad−1AT) synthesized and secreted human 1 AT for 4 weeks. In rats, in vivo intraportal administration of a recombinant Ad containing the E. coli lacZ gene, was followed by expression of −galactosidase in hepatocytes 3 days after infection. Intraportal infusion of Ad−1AT produced detectable serum levels of human 1AT for 4 weeks. Thus, targeted gene expression has been achieved in the liver, albeit at low levels, suggesting that adenovirus vectors may be a useful means for in vivo gene therapy in liver disorders.

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