CATIONIC FACIAL AMPHIPHILES - A PROMISING CLASS OF TRANSFECTION AGENTS

A promising class of compounds for DNA transfection have been designed by conjugating various polyamines to bile-acid-based amphiphiles. For mulations containing these compounds were tested for their ability to facilitate the uptake of a beta-galactosidase reporter plasmid into CO S-7 cells. Dioleoyl phosphatidyl ethanolamine (DOPE) formulations of s ome of the compounds were several times better than Lipofectin at prom oting DNA uptake. The most active compounds contained the most hydroph ilic bile acid components. The activity is clearly not related to affi nity for DNA: the hydrophobic bile acid conjugates were found to form stable complexes with DNA at lower charge ratios than the hydrophilic conjugates. We suggest that the high activity of the best compounds is related to their facial amphiphilicity, which may confer an ability t o destabilize membranes. The success of these unusual cationic transfe ction agents may inspire the design of even more effective gene delive ry agents.