Cationic liposome-DNA complexes: From liquid crystal science to gene delivery applications

Cyrus R. Safinya*, Kai Ewert, Ayesha Anmad, Heather M. Evans, Uri Raviv, Daniel J. Needleman, Alison J. Lin, Nelle L. Slack, Cyril George, Charles E. Samuel, A. S. Matharu, M. H. Li, V. Percec, J. Seddon

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

67 Scopus citations

Abstract

At present, there is an unprecedented level of interest in the properties and structures of complexes consisting of DNA mixed with oppositely charged cationic liposomes (CLs). The interest arises because the complexes mimic natural viruses as chemical carriers of DNA into cells in worldwide human gene therapy clinical trials. However, since our understanding of the mechanisms of action of CL-DNA complexes interacting with cells remains poor, significant additional insights and discoveries will be required before the development of efficient chemical carriers suitable for long-term therapeutic applications. Recent studies describe synchrotron X-ray diffraction, which has revealed the liquid crystalline nature of CL-DNA complexes, and three-dimensional laser-scanning confocal microscopy, which reveals CL-DNA pathways and interactions with cells. The importance of the liquid crystalline structures in biological function is revealed in the application of these modern techniques in combination with functional transfection efficiency measurements, which shows that the mechanism of gene release from complexes in the cell cytoplasm is dependent on their precise liquid crystalline nature and the physical and chemical parameters (for example, the membrane charge density) of the complexes. In §5, we describe some recent new results aimed at developing bionanotube vectors for gene delivery.

Original languageAmerican English
Pages (from-to)2573-2596
Number of pages24
JournalPhilosophical transactions. Series A, Mathematical, physical, and engineering sciences
Volume364
Issue number1847
DOIs
StatePublished - 15 Oct 2006
Externally publishedYes

Keywords

  • Cationic liposomes
  • Gene delivery
  • Gene therapy
  • Liquid crystal phases
  • Synchrotron X-ray scattering
  • Transfection efficiency

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