Polycation liposomes, a novel nonviral gene transfer system, constructed from cetylated polyethylenimine.
A novel gene transfer system was developed by using liposomes modified with cetylated polyethylenimine (PEI, MW 600). This polycation liposome, PCL, showed remarkable transfection efficiency as monitored by the expression of the GFP reporter gene. Most conventional cationic liposomes require phosphatidylethanolamine or cholesterol as a component, although PCLs did not. Egg yolk phosphatidylcholine- and dipalmitoylphosphatidylcholine-based PCL were as effective as dioleoylphosphatidylethanolamine-based PCLs for gene transfer. Concerning the cytotoxicity against COS-1 cells and hemolytic activity, the PCL was superior to conventional cationic liposome preparations. Furthermore, the transfection efficacy of PCLs was enhanced, instead of being diminished, in the presence of serum. Effective gene transfer was observed in all eight malignant and two normal cells line tested, as well as in COS-1 cells. We also examined the effect of the molecular weight of PEI on PCL-mediated gene transfer, and observed that PEI with a MW of 1800 Da was as effective as that with one of 600, but that PEI of 25,000 was far less effective. Finally, an in vivo study was done in which GFP was effectively expressed in mouse liver after injection of PCL via the portal vein. Thus, PCL represents a new system useful for transfection and gene therapy.
Department of Radiobiochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Japan.
Y
Y
Yamazaki
M
M
Nango
M
M
Matsuura
Y
Y
Hasegawa
M
M
Hasegawa
N
N
Oku
D000818:Animals; D019556:COS Cells; D002412:Cations; D015870:Gene Expression; D005822:Genetic Vectors / Q000008:administration & dosage*; D049452:Green Fluorescent Proteins; D008081:Liposomes; D008099:Liver / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics; D011094:Polyethyleneimine; D011169:Portal Vein; D014162:Transfection / Q000379:methods*
D002412:Cations; D008081:Liposomes; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins; D011094:Polyethyleneimine