Synthesis and characterization of aromatic ring-based cationic lipids for gene delivery in vitro and in vivo

A new series of cationic lipids has been synthesized for gene delivery usin g 3,5-dihydroxybenzyl alcohol as the backbone and starting material. Using CMV driven expression system and luciferase gene as a reporter, we demonstr ated that the transfection activity of these new lipids when formulated wit h Tween SO as co-lipid is comparable to that of DOTAP, one of the most comm only used cationic lipids for transfection. Among the four different cell l ines tested including murine melanoma BL-6 cells, human embryonic kidney 29 3 cells, HepG2 and HeLa cells, the highest transgene expression was seen in 293 cells. Results from in vivo experiments using mice as an animal model show that these cationic lipids preferentially transfect the cells in the l ung upon tail vein administration. The cationic lipid, N,N,N-trimethyl-N-[3 ,5-bis(tetradecyloxy)benzyl] ammonium bromide 4c(di-C14 : 0) with two 14-hy drocarbon chains exhibits the best transfection activity, These results sug gest that these new aromatic ring-based cationic lipids are useful transfec tion reagents for both in vitro and in vivo gene transfer studies.