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The in vivo gene transfer to mouse hepatocytes of pTG 7101, a plasmid containing the full-length gene encoding human alpha 1-antitrypsin (alpha 1-AT) DNA, has been studied by iv administration of recombinant DNA (100 ng/mouse) encapsulated in large and small liposomes. Our results from immunohistochemical liver sections and cytophotometric analysis of hepatocyte chromophore absorbance indicate that human alpha 1-AT was expressed in liver parenchymal cells from mice treated (48 hr before) with DNA encapsulated in small liposomes, and this effect remained for at least 2 weeks. In contrast, the efficiency was greatly limited when large liposomes were used as a vehicle for gene transfer. Additional experiments were performed to study using an ELISA procedure the presence in mouse plasma of human alpha 1-AT from mice treated with encapsulated plasmid in small liposomes or small empty liposomes plus free DNA. According to the immunohistochemical data, the results indicate that detectable alpha 1-AT can only be observed in plasma from mice treated with encapsulated plasmid in small liposomes.

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