Phase diagram of 3β -[N-(N,N -dimethylaminoethane)-carbamoyl]- cholesterol-dioleoylphosphatidylethanolamine/DNA complexes suggests strategies for efficient lipoplex transfection

Synchrotron small angle x-ray scattering and electrophoresis on agarose gels have been applied to construct the phase diagram of the ternary complex made up of the cationic lipid 3 beta-[N-(N,N-dimethylaminoethane)-carbamoyl]-cholesterol, the neutral lipid dioleoylphosphatidylethanolamine and DNA. We show that nominally charge-neutral complexes coexist with free DNA, while excess cationic charge is necessary to protect all the genetic cargo. Such an extra-charge requirement diminishes as the molar fraction of neutral lipid in the bilayer increases. Furthermore, complexes with very different membrane composition and charge ratio exhibit the very same DNA protection ability. The relevance of results for transfection studies is discussed. (C) 2010 American Institute of Physics. [doi:10.1063/1.3427394