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 i n vivo human alpha 1-antitrypsin (AAT) gene transfer was studied in mi ce with and without an associated partial hepatectomy. The pTG7101 pla smid, containing the full-length human AAT gene, was encapsulated in s mall liposomes bearing 10% of negatively (phosphatidylserine, PS) or p ositively (DOTAP) charged lipids. The results indicate that the DNA/li pid ratio was increased in cationic liposomes by inclusion of monosial oganglioside-G(M1). The expression of human protein after in vivo gene transfer was quantified in mouse plasma by an ELISA procedure, and re vealed that both anionic and cationic liposomes mediated the presence of human protein in mouse plasma for 2-3 weeks. This effect was prolon ged (>5 months) when a partial hepatectomy was performed after treatme nt. In addition, it was observed that the efficacy of liposome-mediate d gene transfer was more limited when the plasmid was externally assoc iated to cationic liposomes.