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A plasmid (pTG7101) containing the full-length human alpha 1-antitrypsin gene was encapsulated in small liposomes and used for "in vivo" gene transfer to mouse hepatocytes, by i.v. injection (100 ng DNA/mouse and dose). The expression of human protein was evaluated by microspectrophotometry after human alpha 1-antitrypsin immunoperoxidase reaction on liver cryosections and the presence in mouse plasma of de novo synthesized 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 when mice were treated with buffer or free plasmid (100 ng/mouse) plus an equivalent lipid dose of empty liposomes. In addition, whereas no additive effect was observed after repetitive treatment-doses, the partial hepatectomy three hours after a single treatment-dose, significantly increased the presence of human alpha 1-antitrypsin in mice plasma.
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