title: A dialkynoyl analogue of DOPE improves gene transfer of lower-charged, cationic lipoplexes.
abstract: Positively-charged gene delivery agents, such as cationic liposomes, typically prepared by mixing a cationic lipid and a neutral lipid in a 1 : 1 molar ratio, exhibit a fundamental flaw: on the one hand, the charge encourages cell uptake; on the other hand, the charge leads to aggregation in vivo with anionic serum components. We herein report a more phase-stable analogue of the zwitterionic and fusogenic lipid DOPE that allows for the reduction of the cationic lipid component of the liposome from 50 to 9 mol% with almost no apparent loss in transfection activity. This reduction in charge may induce important in vivo stability whilst still imparting high cell uptake and transgene expression.
authors.affiliation: Imperial College Genetic Therapies Centre, Department of Chemistry, Flowers Building, Armstrong Road, Imperial College London, London, UK SW7 2AZ.
authors.forename: Steven
authors.initials: S
authors.lastname: Fletcher
authors.forename: Ayesha
authors.initials: A
authors.lastname: Ahmad
authors.forename: Eric
authors.initials: E
authors.lastname: Perouzel
authors.forename: Michael R
authors.initials: MR
authors.lastname: Jorgensen
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Miller
mesh_terms: D002412:Cations; D004355:Drug Stability; D015316:Genetic Therapy / Q000379:methods; D008081:Liposomes / Q000737:chemistry* / Q000493:pharmacokinetics; D010714:Phosphatidylethanolamines / Q000737:chemistry* / Q000235:genetics; D014162:Transfection / Q000379:methods* / Q000592:standards
chemical_list: C410262:1,2-dioleoyl-glycero-3-phosphatidyl ethanolamine; D002412:Cations; D008081:Liposomes; D010714:Phosphatidylethanolamines