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Cationic Lipids: Molecular Structure/Transfection Activity Relationships and Interactions with Biomembranes

Chapter
Part of the Topics in Current Chemistry book series (TOPCURRCHEM, volume 296)

Abstract

Synthetic cationic lipids, which form complexes (lipoplexes) with polyanionic DNA, are presently the most widely used constituents of nonviral gene carriers. A large number of cationic amphiphiles have been synthesized and tested in transfection studies. However, due to the complexity of the transfection pathway, no general schemes have emerged for correlating the cationic lipid chemistry with their transfection efficacy and the approaches for optimizing their molecular structures are still largely empirical. Here we summarize data on the relationships between transfection activity and cationic lipid molecular structure and demonstrate that the transfection activity depends in a systematic way on the lipid hydrocarbon chain structure. A number of examples, including a large series of cationic phosphatidylcholine derivatives, show that optimum transfection is displayed by lipids with chain length of ∼14 carbon atoms and that the transfection efficiency strongly increases with increase of chain unsaturation, specifically upon replacement of saturated with monounsaturated chains.

Keywords

Cationic lipid Lipoplex Nucleic acid Phase transition Transfection 

Notes

Acknowledgments

The present work was supported by NSF grant EEC-0425626 and in part by NIH grant CA119341.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2010

Authors and Affiliations

  1. 1.Ohio State University College of PharmacyColumbusUSA
  2. 2.Northwestern UniversityEvanstonUSA
  3. 3.Bulgarian Academy of SciencesSofiaBulgaria

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