In vitro gene transfer with a novel galactosylated spermine bolaamphiphile

We describe the synthesis of a alpha -galacto-omega -spermine bolaamphiphil e (GalSper) and report on the gene transfer mediated with lipoplexes it for ms either when used alone or in conjunction with DOPE or with DOGS (Transfe ctam). Lipofection with GalSper was investigated with human HepG2 or murine BNL-CL2 hepatocytes expressing the asialo-glycoprotein (ASGP) receptor, wh ich displays a high affinity for galactosyl residues, or with A549 cells wh ich do not express ASGP. Although lower luciferase expression levels in BNL -CL2 and in HepG2 cells were obtained with GalSper/DOPE N/P 2.5 lipoplexes as compared with control DOGS/DOPE N/P 2.5 particles or with the more posit ively charged N/P 5 particles (yet through a different mechanism), specific receptor-mediated endocytosis of DNA can be achieved with this targeted ca tionic GalSper bolaamphiphile presenting a single galactose residue. The pr esent work suggests that GalSper-based DNA formulations appear as promising synthetic vectors for specific gene delivery to ASGP(+) cells.