title: In vitro gene transfer with a novel galactosylated spermine bolaamphiphile.
abstract: We describe the synthesis of a alpha-galacto-omega-spermine bolaamphiphile (GalSper) and report on the gene transfer mediated with lipoplexes it forms either when used alone or in conjunction with DOPE or with DOGS (Transfectam). Lipofection with GalSper was investigated with human HepG2 or murine BNL-CL2 hepatocytes expressing the asialo-glycoprotein (ASGP) receptor, which displays a high affinity for galactosyl residues, or with A549 cells which 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 positively charged N/P 5 particles (yet through a different mechanism), specific receptor-mediated endocytosis of DNA can be achieved with this targeted cationic GalSper bolaamphiphile presenting a single galactose residue. The present work suggests that GalSper-based DNA formulations appear as promising synthetic vectors for specific gene delivery to ASGP(+) cells.
authors.affiliation: Laboratoire de Chimie Bioorganique, UMR 6001 CNRS-Université de Nice Sophia-Antipolis, Faculté des Sciences, 06108 Nice Cédex 2, France.
authors.forename: J
authors.initials: J
authors.lastname: Gaucheron
authors.forename: C
authors.initials: C
authors.lastname: Santaella
authors.forename: P
authors.initials: P
authors.lastname: Vierling
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000737:chemistry; D005227:Fatty Acids / Q000138:chemical synthesis; D005690:Galactose / Q000737:chemistry*; D018014:Gene Transfer Techniques / Q000639:trends; D020404:Glycerophospholipids / Q000737:chemistry; D005998:Glycine / Q000031:analogs & derivatives / Q000737:chemistry; D022781:Hepatocytes / Q000166:cytology; D006801:Humans; D008156:Luciferases / Q000187:drug effects* / Q000235:genetics; D046911:Macromolecular Substances; D051379:Mice; D009005:Monosaccharides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D010316:Particle Size; D010714:Phosphatidylethanolamines; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000235:genetics; D010980:Platelet Membrane Glycoproteins; D013096:Spermine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D014162:Transfection
chemical_list: C410262:1,2-dioleoyl-glycero-3-phosphatidyl ethanolamine; D005227:Fatty Acids; C436394:GalSper; D020404:Glycerophospholipids; D046911:Macromolecular Substances; D009005:Monosaccharides; D010714:Phosphatidylethanolamines; D019038:Platelet Glycoprotein GPIb-IX Complex; D010980:Platelet Membrane Glycoproteins; C032193:glycoprotein receptor GPIb-IX; C061134:dioctadecylamidoglycylspermine; D013096:Spermine; D004247:DNA; D008156:Luciferases; D005998:Glycine; D005690:Galactose