Cationic lipid-DNA complexes-lipoplexes-for gene transfer and therapy.
Cationic lipid-mediated gene transfer and delivery still attract great attention of many gene therapy laboratories. From the point of view of the most important characteristics of lipoplex particles, e.g. its charge and size, we reviewed recent studies available. In general, the paper deals with non-viral systems of gene transfer into eukaryotic cell based on various lipids. Having usually less efficiency in gene transfer, lipid-based gene transfer vehicles (lipoplexes/genosomes) are characterized with certain advantages even over viral ones: they are less toxic and immunogenic, could be targetable and are easy for large-scale production, a size of transferred DNA being quite high. Conditions of DNA condensation during interactions with lipids are described. Results of the studies of mechanism of DNA-lipid complex interactions with the cell membrane and their transport into the nucleus are summarized. Dependence of efficiency of gene transfer on lipoplex structure and physical-chemical properties is reviewed. Advantages and disadvantages of different macromolecule complexes from the point of view of transfection efficiency, possibility of use in vivo, cytotoxicity and targeted gene transfer in certain organs and tissues are also discussed. Results of transfection of different cells using neutral, anion and cation liposomes are reviewed. The conclusion reached was that efficiency and specificity of gene transfer may grow considerably when mixed macromolecule lipid systems including polycations and glycolipids are used.
Zhdanov
R I
RI
V N Orekhovich Institute of Biomedical Chemistry, Russian Academy of Medical Sciences, 10, Pogodinskaya Street, 119832, Moscow, Russian Federation. renat@ibmh.msk.su
Podobed
O V
OV
Vlassov
V V
VV
D000818:Animals; D004247:DNA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes; D019076:Transgenes / Q000235:genetics
D008055:Lipids; D008081:Liposomes; D004247:DNA