Novel Zwitterionic Liposome Approaches to Lipid Based Nucleic Acid Delivery

J. Nguyen, C. Walsh, M. Motion, F.C. Szoka
University of California, San Francisco, US

Keywords: nucleic acid delivery


The application of gene and RNAi therapy in the clinic requires safe and efficient vectors. To date the two main chemical approaches for non-viral nucleic acid therapy are based on lipids or polymers. In 1987, Felgner introduced DOTMA, the first cationic lipid for DNA transfection. Since then, a large variety of cationic lipids have been developed. Cationic lipids are effective but they also activate the immune system. Our group has recently developed a series of zwitterionic lipids and novel enzyme-triggered fusion peptides that can be incorporated into liposomes. These systems are activated within cells by low pH or compartmentalized enzymes, to release their contents and transfer them into the cytoplasm. The systems do not induce the secretion of cytokines or chemokines after intravenous administration in mice. Hence they are potential alternatives to the currently available cationic lipids for gene and siRNA delivery in animals and man. This work is supported by NIH EB0003008.