Single additional methylene group in the head-group region imparts high gene transfer efficacy to a transfection-incompetent cationic lipid

Abstract

In combination with equimolar 1,2-dioleoyl-L-α-glycero-3-phosphatidyl ethanolamine, a novel cholesterol-based cationic lipid with β-alanine head-group (2) has been demonstrated to be strikingly more efficacious (10-24-fold) in transfecting CHO, COS-1 and HepG2 cells than its glycine analog (1) containing just one less methylene unit in its head-group region. Syntheses, characterizations and in vitro transfection biology of lipids 1 and 2 are described. Present findings demonstrate that even truly minor structural alterations, such as inclusion of just one additional methylene functionality in the polar head-group region, can convert an essentially transfection-incompetent cholesterol-based cationic amphiphile to a remarkably efficient cationic transfection lipid.