Synthesis and properties of novel tetraalkyl cationic lipids.
The synthesis, physical properties, and transfection potencies of two representives of a new class of divalent, tetraalkyl cationic lipids is described. These cationic lipids are dimers of N,N-Dioleyl-N,N-dimethylammonium chloride (DODAC) joined by a hydrocarbon tether three or six carbons in length (TODMAC3 and TODMAC6, respectively). It is shown that TODMAC6 can display improved transfection properties in comparison to DODAC when formulated into plasmid DNA-cationic lipid complexes. These improved transfection potencies are observed at cationic lipid to DNA charge ratios of two or higher. It is also shown that TODMAC6 exhibits equivalent or improved ability (as compared to DODAC) to induce nonbilayer structure in mixtures with anionic lipid. This is consistent with the hypothesis that the ability of cationic lipids to induce nonbilayer structures when mixed with anionic lipids is correlated to their transfection potency. Complexes containing TODMAC3 on the other hand exhibit lower transfection potencies than achieved with DODAC, behavior that is consistent with steric effects limiting the formation of ion pairs with anionic lipids. It is concluded that TODMAC6 exhibits potential as a transfection agent for in vitro and in vivo use and that the design of cationic lipids according to their ability to induce nonbilayer structure provides a useful guide for synthesis of new cationic lipids.
Gaucheron
Jérôme
J
Department of Biochemistry and Molecular Biology, University of British Columbia, 2146 Health Sciences Mall, Vancouver, BC, Canada V6T 1Z3. jerome_gaucheron@yahoo.fr
Wong
Tabitha
T
Wong
Kim F
KF
Maurer
Norbert
N
Cullis
Pieter R
PR
D002412:Cations / Q000737:chemistry / Q000378:metabolism*; D002478:Cells, Cultured / Q000737:chemistry / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism; D008055:Lipids / Q000138:chemical synthesis* / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D010957:Plasmids; D000644:Quaternary Ammonium Compounds / Q000737:chemistry / Q000378:metabolism*; D014162:Transfection
D002412:Cations; D008055:Lipids; D000644:Quaternary Ammonium Compounds; D004247:DNA