AI Article Synopsis
- Lipidic amphiphiles with trans-2-aminocyclohexanol (TACH) are innovative pH-sensitive "flipids" that can disrupt lipid bilayers when acidity increases.
- Researchers designed and tested various TACH-based lipids within lipoplexes that combine cationic lipid DOTAP and plasmid DNA for gene delivery.
- The TACH-lipid lipoplexes demonstrated significantly improved gene transfection efficiency compared to traditional helper lipids while maintaining similar levels of toxicity.
Article Abstract
Lipidic amphiphiles equipped with the trans-2-aminocyclohexanol (TACH) moiety are promising pH-sensitive conformational switches ("flipids") that can trigger a lipid bilayer perturbation in response to increased acidity. Because pH-sensitivity was shown to improve the efficiency of several gene delivery systems, we expected that such flipids could significantly enhance the gene transfection by lipoplexes. Thus a series of novel lipids with various TACH-based head groups and hydrocarbon tails were designed, prepared and incorporated into lipoplexes that contain the cationic lipid 1,2-dioleoyl-3-trimethylammonio-propane (DOTAP) and plasmid DNA encoding a luciferase gene. B16F1 and HeLa cells were transfected with such lipoplexes in both serum-free and serum-containing media. The lipoplexes consisting of TACH-lipids exhibited up to two orders of magnitude better transfection efficiency and yet similar toxicity compared to the ones with the conventional helper lipids 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) or cholesterol. Thus, the TACH-lipids can be used as novel helper lipids for efficient gene transfection with low cytotoxicity.
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| http://dx.doi.org/10.1016/j.bbamem.2015.08.021 | DOI Listing |
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