EXPRESSION OF HUMAN ALPHA-1-ANTITRYPSIN IN MOUSE AFTER IN-VIVO GENE-TRANSFER TO HEPATOCYTES BY SMALL LIPOSOMES

A plasmid (pTG7101) containing the full-length human alpha 1-antitryps in gene was encapsulated in small liposomes and used for ''in vivo'' g ene transfer to mouse hepatocytes, by i.v. injection (100 ng DNA/mouse and dose). The expression of human protein was evaluated by microspec trophotometry after human alpha 1-antitrypsin immunoperoxidase reactio n on liver cryosections and the presence in mouse plasma of de novo sy nthesized protein was detected by ELISA analysis. Our results indicate that a single dose of encapsulated plasmid induces the expression of human alpha 1-antitrypsin in mouse hepatocytes and a large effect (70% ) remains two weeks after treatment. However, no effect was observed w hen mice were treated with buffer or free plasmid (100 ng/mouse) plus an equivalent lipid dose of empty liposomes. In addition, whereas no a dditive effect was observed after repetitive treatment-doses, the part ial hepatectomy three hours after a single treatment-dose, significant ly increased the presence of human alpha 1-antitrypsin in mice plasma. (C) 1994 Academic Press, Inc.