Cationic lipids, lipoplexes and intracellular delivery of genes

As a consequence of several setbacks encountered by viral technology in achieving efficient and safe gene therapy in clinical trials, non-viral gene delivery vectors are considered to date as a valuable alternative and to hold promise for future therapeutic applications. Nevertheless, the transfection efficiency mediated by these non-viral gene delivery vectors has to be improved, especially in vivo, to benefit fully from their advantages. Cationic lipid/nucleic acid complexes or lipoplexes have been the subject of intensive investigations in recent years to understand the parameters governing the efficiency of transfection. Specifically, the comprehension of such mechanisms, from the formation of the complexes to their intracellular delivery, will lead to the design of better adapted non-viral vectors for gene therapy applications. Here, we will discuss some recent developments in the field on the structure/function relationship of cationic lipids in the mechanism of transfection, and where appropriate, we will make a comparison with mechanisms of viral and polyplex-mediated gene delivery. Cationic lipids are often used in combination with helper lipids such as DOPE or cholesterol. The effect of DOPE on lipoplex assembly and the relevance of the structural properties of the lipoplexes in destabilizing endosomal membranes and mediating endosomal escape of DNA will be discussed. (c) 2006 Elsevier B.V. All rights reserved.