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.