Packing DNA with disc-shaped bicelles

Abstract

Cationic lipid–DNA (CL–DNA) complexes can be used as non-viral vectors to improve transfection efficiency in gene therapy. It is greatly desirable to develop new ways of packing DNA in order to make breakthroughs on the development of highly efficient DNA delivery systems. Different from the widely-studied vesicle based CL–DNA complexes, we have developed a novel cationic bicelle–DNA complex system by mixing cationic bicelles with DNA to form alternating stacks of disc bilayered plates and DNA arrays with a repeat distance of 7.5 nm. SAXS and TEM studies revealed that the DNA molecules encapsulated between the disc bilayered plates form ordered arrays with a spacing of around 4–5 nm. The number of stacking layers can be easily tuned from just a few layers to more than one hundred layers by adjusting the doping percentage of the charged lipids. This CB–DNA complex is quite stable against increases in temperature above the chain-melting temperature of the long chain lipids. Due to the flexible size tunability (number of stacking layers) and the unique structure of the packing of the DNA arrays with 50–100 nm size disc bilayered plates, the CB–DNA complexes are promising as novel non-viral vectors for gene delivery.