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 wi...

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Bibliographic Details
Published in:Organic & biomolecular chemistry 2006-01, Vol.4 (2), p.196-199
Main Authors: Fletcher, Steven, Ahmad, Ayesha, Perouzel, Eric, Jorgensen, Michael R, Miller, Andrew D
Format: Article
Language:English
Subjects:
Cations
Drug Stability
Genetic Therapy - methods
Liposomes - chemistry
Liposomes - pharmacokinetics
Phosphatidylethanolamines - chemistry
Phosphatidylethanolamines - genetics
Transfection - methods
Transfection - standards
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Summary: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.
ISSN:1477-0520
1477-0539
DOI:10.1039/b514532e