Evaluation of cationic liposome suitable for gene transfer into pregnant animals.
Cationic liposome-mediated in vivo gene transfer represents a promising approach for somatic gene therapy. To assess the most suitable liposome for gene delivery into a wide range of organs and fetuses in mice, we have explored several types of cationic liposomes conjugated with plasmid DNA carrying the beta-galactosidase gene through intravenous injection into pregnant animals. Transduction efficiency was assessed by Southern blot analysis and expression of the transferred gene was evaluated by enzymatic demonstration of beta-galactosidase activity. Through the analysis of several types of recently synthesized cationic liposome/lipid formulations, DMRIE-C reagent, a liposome formulation of the cationic lipid DMRIE (1, 2-dimyristyloxypropyl-3-dimethyl-hydroxy ethyl ammonium bromide) and cholesterol in membrane-filtered water met our requirements. When the plasmid DNA/DMRIE-C complexes were administered intravenously into pregnant mice at day 11.5 post coitus (p.c.), transferred genes were observed in several organs in dams and were expressed. Furthermore, although the copy numbers transferred into embryos were low, we observed reporter gene expression in the progeny.
D000818:Animals; D002412:Cations; D004247:DNA; D005069:Evaluation Studies as Topic; D005260:Female; D015870:Gene Expression; D018014:Gene Transfer Techniques; D008055:Lipids; D008081:Liposomes; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010957:Plasmids; D011247:Pregnancy; D000644:Quaternary Ammonium Compounds; D001616:beta-Galactosidase / Q000235:genetics