A dialkynoyl analogue of DOPE improves gene transfer of lower-charged, cationic lipoplexes.
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.
Fletcher
Steven
S
Imperial College Genetic Therapies Centre, Department of Chemistry, Flowers Building, Armstrong Road, Imperial College London, London, UK SW7 2AZ.
Ahmad
Ayesha
A
Perouzel
Eric
E
Jorgensen
Michael R
MR
Miller
Andrew D
AD
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
C410262:1,2-dioleoyl-glycero-3-phosphatidyl ethanolamine; D002412:Cations; D008081:Liposomes; D010714:Phosphatidylethanolamines