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 (alpha 1-AT) DNA, has been studied by iv administration of recombinant DNA (100 ng/mouse) encapsulated in large and small liposomes. Our results from immunohistochemical liver sections and cytophotometric analysis of hepatocyte chromophore absorbance indicate that human alpha 1-AT was expressed in liver parenchymal cells from mice treated (48 hr before) 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. Additional experiments were performed to study using an ELISA procedure the presence in mouse plasma of human alpha 1-AT from mice treated with encapsulated plasmid in small liposomes or small empty liposomes plus free DNA. According to the immunohistochemical data, the results indicate that detectable alpha 1-AT can only be observed in plasma from mice treated with encapsulated plasmid in small liposomes.
Aliño
S F
SF
Department of Pharmacology, Faculty of Medicine and Dentistry, University of Valencia, Spain.
Bobadilla
M
M
Crespo
J
J
Lejarreta
M
M
D000818:Animals; D018014:Gene Transfer Techniques; D006801:Humans; D008081:Liposomes / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D000515:alpha 1-Antitrypsin / Q000235:genetics* / Q000378:metabolism
D008081:Liposomes; D000515:alpha 1-Antitrypsin