Efficient gene transfection by bisguanylated diacetylene lipid formulations

We have previously shown that cationic cholesterol derivatives bearing guan idinium groups were efficient vectors for gene transfer. To further evaluat e the potentiality of this novel class of cationic lipids, we undertook to study the transfection efficiency of guanidinium-based lipids with other hy drophobic moieties, Specifically, we synthesized a reagent where two guanid inium groups are linked to a diacetylene lipid which may provide the lipopl exes with favorable structural features. We report here that the cationic l ipid disguanidinium-diacetylene (BGDA) is highly efficient for in vitro gen e transfection when formulated with dioleoylphosphatidyl ethanolamine (DOPE ), We also show that liposomes composed of BGDA, DOPE, and a neutral diacet ylene colipid, hydroxyethylenediacetylene (HEDA), are efficient for transfe ction, Thus, diacetylene-based lipids provide a novel scaffold for gene tra nsfection and will be particularly useful for gaining new insights into the structure-activity relationships of the lipid/DNA complexes as they offer a means to study the effects of polymerizable domains. (C) 2001 Academic Pr ess.