Long-term expression of the human alpha 1-antitrypsin gene in mice employing anionic and cationic liposome vectors

The efficiency of both anionic and cationic liposomes as vectors for in vivo human alpha 1-antitrypsin (AAT) gene transfer was studied in mice with and without an associated partial hepatectomy. The pTG7101 plasmid, containing the full-length human AAT gene, was encapsulated in small liposomes bearing 10% of negatively (phosphatidylserine, PS) or positively (DOTAP) charged lipids. The results indicate that the DNA/lipid ratio was increased in cationic liposomes by inclusion of monosialoganglioside-G(M1). The expression of human protein after in vivo gene transfer was quantified in mouse plasma by an ELISA procedure, and revealed that both anionic and cationic liposomes mediated the presence of human protein in mouse plasma for 2-3 weeks. This effect was prolonged (>5 months) when a partial hepatectomy was performed after treatment. In addition, it was observed that the efficacy of liposome-mediated gene transfer was more limited when the plasmid was externally associated to cationic liposomes.