The effect of lipid composition on receptor-mediated in vivo gene transfection using mannosylated cationic liposomes in mice

The effect of the lipid composition of mannosylated cationic liposomes on in vivo transfection of plasmid DNA in a complex form via receptor-mediated endocytosis was studied. N-[1-(2,3-dioleyloxy) propyl]-n,n,n-trimethylammonium chloride (DOTMA)/cholesterol (Chol)/cholesten-5-yloxy-N-(4-((1-iminto-2 -beta -D-thiomannosyl-ethyl)amino)butyl)formamide (Man-C4-Chol) (1/0.5/0.5), Man-C4-Chol/DOPE (3/2), and DOTMA/Chol (1/1) liposomes complexed with plasmid DNA-encoding luciferase gene (pCMV-Luc) were compared via intravenous and intraportal injections in mice. The control cationic DOPE/Chol liposome showed the highest gene expression in the lung with both injection routes. On the other hand, the highest gene expression was observed in the liver after intravenous and intraportal injection of Man-C4-Chol/DOPE liposome/DNA complexes. In the case of DOTMA/Chol/Man-C4-Chol liposome, the highest gene expression was observed in the liver by intravenous injection, but intraportal injection gave high expression in the lung. These results suggest the possibility of improved transfection efficacies through lipid composition control in hepatic gene delivery using mannosylated liposomes.