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On the mechanism whereby cationic lipids promote intracellular delivery of polynucleic acids

Gene Therapy volume 8, pages 1188–1196 (2001)Cite this article

Abstract

The mechanism whereby cationic lipids destabilize cell membranes to facilitate the intracellular delivery of macromolecules such as plasmid DNA or antisense oligonucleotides is not well understood. Here, we show that cationic lipids can destabilize lipid bilayers by promoting the formation of nonbilayer lipid structures. In particular, we show that mixtures of cationic lipids and anionic phospholipids preferentially adopt the inverted hexagonal (HII) phase. Further, the presence of ‘helper’ lipids such as dioleoylphosphatidylethanolamine or cholesterol, lipids that enhance cationic lipid-mediated transfection of cells also facilitate the formation of the HII phase. It is suggested that the ability of cationic lipids to promote nonbilayer structures in combination with anionic phospholipids leads to disruption of the endosomal membrane following uptake of nucleic acid–cationic lipid complexes into cells, thus facilitating cytoplasmic release of the plasmid or oligonucleotide.

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Acknowledgements

This work was supported by the Medical Research Council of Canada. IMH acknowledges support from the Science Council of British Columbia in the form of a GREAT award.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada

    IM Hafez, N Maurer & PR Cullis

  2. Inex Pharmaceuticals Corporation, Burnaby, BC, Canada

    PR Cullis

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  1. IM Hafez
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  2. N Maurer
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Hafez, I., Maurer, N. & Cullis, P. On the mechanism whereby cationic lipids promote intracellular delivery of polynucleic acids. Gene Ther 8, 1188–1196 (2001). https://doi.org/10.1038/sj.gt.3301506

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