Polycation liposome-mediated gene transfer in vivo.
The polycation liposome (PCL), a recently developed gene transfer system, is simply prepared by a modification of liposomes with cetylated polyethylenimine (PEI), and shows remarkable transgene efficiency with low cytotoxicity. In the present study, we investigated the applicability of PCLs for in vivo gene transfer, since the PCL-mediated transgene efficiency was found to be maintained in the presence of serum. PCLs composed of dioleoylphosphatidylethanolamine (DOPE) with 5 mol% cetyl PEI (PEI average mr. wt. 1800), were superior for transfection to those of dipalmitoylphosphatidylcholine (DPPC) and cholesterol (2:1 as molar ratio) with 5 mol% cetyl PEI in vitro, although the latter PCLs were more efficient for gene transfer in vivo. PCL-DNA complexes were injected into mice via a tail or the portal vein, with the DNA being a plasmid encoding green fluorescent protein (GFP) or luciferase; and the expression was monitored qualitatively or quantitatively, respectively. Tail vein injection resulted in high expression of both GFP and luciferase genes in lung, and portal vein injection resulted in high expression of both genes in the liver. Concerning the gene delivery efficiency, the PCL was found to be superior to PEI or cetyl PEI alone. The optimal conditions for in vivo transfection with PCLs were also examined.
Matsuura
Mitsuo
M
Department of Medical Biochemistry, University of Shizuoka School of Pharmaceutical Sciences, Yada, Shizuoka, Japan.
Yamazaki
Yukako
Y
Sugiyama
Mayu
M
Kondo
Masami
M
Ori
Hidetsugu
H
Nango
Mamoru
M
Oku
Naoto
N
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D002412:Cations / Q000737:chemistry*; D002460:Cell Line; D002784:Cholesterol / Q000737:chemistry / Q000378:metabolism; D004247:DNA / Q000235:genetics / Q000378:metabolism; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D015394:Molecular Structure; D010714:Phosphatidylethanolamines / Q000737:chemistry / Q000378:metabolism; D011094:Polyethyleneimine / Q000737:chemistry
C410262:1,2-dioleoyl-glycero-3-phosphatidyl ethanolamine; D002412:Cations; D008081:Liposomes; D010714:Phosphatidylethanolamines; D015060:1,2-Dipalmitoylphosphatidylcholine; D011094:Polyethyleneimine; D004247:DNA; D002784:Cholesterol