ABSTRACT

Cationic lipids have been widely studied as a means of nucleic acid delivery. These amphiphilic dialkyl molecules allow for high association with DNA, thanks to electrostatic interactions. DNA has been shown to locate at the interlamellar spacings, interacting strongly with the cationic polar group of the lipids (1). Release of phosphate counterions and circular dichroism studies the nature of supercoiled DNA in these structures (2). These complexes efficiently deliver DNA to the cells. They are actively used in vitro to test new DNA clones or transiently express a protein of interest. In contrast, their in vivo applications have been limited due to numerous nonspecific interactions of the cationic lipid/DNA complexes, which are called lipoplexes, upon intravenous injection. These interactions either render lipoplexes unavailable for the target of interest, in particular because of their interaction with lung endothelium, or lead to fast elimination through seric protein

association or complement activation. Moreover, toxicity has been attributed to platelet aggregation and complement activation by cationic lipoplexes.