Head group configuration increases the biocompatibility of cationic lipids for nucleic acid delivery

Intracellular delivery of genetic material is a potentially powerful therapeutic approach for the treatment of genetic diseases. However, the scarcity of biocompatible delivery systems is a tremendous barrier for the application of nucleic acid therapy in the clinic. Herein, we successfully created biocompatible nucleic acid delivery systems based on cationic lipids consisting of alternatively linked ornithine residues in the head group (denoted DoGo lipids). Transfection of the pcDNA3-eGFP plasmid into cells using DoGo lipids resulted in significant transfection efficiency without showing any apparent cytotoxicity. Meanwhile, DoGo lipids efficiently delivered siRNA to cancer cell lines and induced profound RNAi activity at a siRNA concentration as low as 5 nM. DoGo lipid driven delivery of a siRNA against polo-like kinase 1 (Plk1) in cancer cells induced significant morphological changes in the cell and the nucleus due to cell cycle arrest and inhibition of cell proliferation, a phenotype resulting from the decreased Plk1 protein level. Our findings demonstrate that DoGo lipids have great potential in clinical application for gene based therapy.