Cationic Liposomes as an Oligonucleotide Carrier: Mechanism of Action

Cationic liposomes are a useful in vitro but as yet unproven in vivo delivery system for oligonucleotides. An understanding of the mechanism of delivery mediated by cationic lipid/oligonucleotide complexes has been lacking. In this review, we describe recent results concerning several steps of the delivery process, including the formation of complexes, the intracellular distribution of the oligonucleotide and the lipid, as well as the uptake pathway and site of intracellular release. Cationic liposomes form a polyelectrolyte complex with the oligonucleotides, protect them from nuclease degradation, enhance their cellular uptake and improve the oligonucleotide potency. In the majority of cell types studied, cationic lipids deliver oligonucleotides into the cell predominately via an endocytotic pathway rather then by fusion with the plasma membrane. We propose that the oligonucleotide is released from the complex when anionic lipids from the cytoplasmic facing lipid monolayer of the cell flip into c...