DNA complexes with reducible cationic lipid for gene transfer

This chapter deals with the cationic lipids developed and investigated as an alternative to viral vectors for gene therapy. They are able to associate with the DNA by ionic attraction and protect it from nucleases in biological media. Lipoplexes are readily taken up in vitro in numerous cell types. Several limiting steps take place after lipoplexes enter the cells. For efficient transfection to occur, DNA should be released from the complexes that have been localized by electron microscopy in intracellular vesicular structures. Plasmids have been shown to present a very limited mobility in the cytoplasm, thereby rendering them susceptible to nuclease degradation before reaching the nucleus. Cell division plays an essential role to reach high transfection efficacy. To improve DNA release from its cationic vector, lipids susceptible to esterase hydrolysis have been synthesized. This approach showed increased in vitro transfection efficiency and reduced cytotoxicity but could not be applied to polyamines because of intramolecular side reactions. It may also suffer from decreased stability when delivered in vivo.