European Biophysics Journal

, Volume 41, Issue 10, pp 815–829

Cationic liposome/DNA complexes: from structure to interactions with cellular membranes

Review

Abstract

Gene-based therapeutic approaches are based upon the concept that, if a disease is caused by a mutation in a gene, then adding back the wild-type gene should restore regular function and attenuate the disease phenotype. To deliver the gene of interest, both viral and nonviral vectors are used. Viruses are efficient, but their application is impeded by detrimental side-effects. Among nonviral vectors, cationic liposomes are the most promising candidates for gene delivery. They form stable complexes with polyanionic DNA (lipoplexes). Despite several advantages over viral vectors, the transfection efficiency (TE) of lipoplexes is too low compared with those of engineered viral vectors. This is due to lack of knowledge about the interactions between complexes and cellular components. Rational design of efficient lipoplexes therefore requires deeper comprehension of the interactions between the vector and the DNA as well as the cellular pathways and mechanisms involved. The importance of the lipoplex structure in biological function is revealed in the application of synchrotron small-angle X-ray scattering in combination with functional TE measurements. According to current understanding, the structure of lipoplexes can change upon interaction with cellular membranes and such changes affect the delivery efficiency. Recently, a correlation between the mechanism of gene release from complexes, the structure, and the physical and chemical parameters of the complexes has been established. Studies aimed at correlating structure and activity of lipoplexes are reviewed herein. This is a fundamental step towards rational design of highly efficient lipid gene vectors.

Keywords

Gene therapy Gene delivery Cationic liposomes DNA Lipoplexes Cellular lipids 

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Copyright information

© European Biophysical Societies' Association 2012

Authors and Affiliations

  1. 1.Department of Molecular Medicine“Sapienza” University of RomeRomeItaly
  2. 2.Institute of Biophysics and Nanosystems ResearchAustrian Academy of SciencesGrazAustria

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