HUMAN ALPHA-1-ANTITRYPSIN GENE-TRANSFER TO IN-VIVO MOUSE HEPATOCYTES

The in vivo gene transfer to mouse hepatocytes of pTG 7101, a plasmid containing the full-length gene encoding human alpha 1-antitrypsin (al pha 1-AT) DNA, has been studied by iv administration of recombinant DN A (100 ng/mouse) encapsulated in large and small liposomes. Our result s from immunohistochemical liver sections and cytophotometric analysis of hepatocyte chromophore absorbance indicate that human alpha 1-AT w as expressed in liver parenchymal cells from mice treated (48 hr befor e) 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. Additio nal experiments were performed to study using an ELISA procedure the p resence in mouse plasma of human alpha 1-AT from mice treated with enc apsulated plasmid in small liposomes or small empty liposomes pins fre e DNA. According to the immunohistochemical data, the results indicate that detectable alpha 1-AT can only be observed in plasma from mice t reated with encapsulated plasmid in small liposomes.