查看文章

The prospects of gene therapy have generated unprecedented interest in the properties and structures of complexes of nucleic acids (NAs) with cationic liposomes (CLs), which are used as nonviral NA carriers in worldwide clinical trials. An improved understanding of the mechanisms of action of CL−NA complexes is required to enable their widespread therapeutic use. In prior studies of CL-mediated DNA delivery, membrane charge density (σ_M) was identified as a key parameter for transfection efficiency (TE) of lamellar (L_α^C) CL−DNA complexes. The TE of CL−DNA complexes containing cationic lipids with headgroup valencies from 1+ to 5+ follows a universal bell-shaped curve as a function of σ_M. As we report here, the TE of CL−DNA complexes containing new multivalent lipids with dendritic headgroups (DLs) strongly deviates from this curve at high σ_M. We have investigated four DLs, MVLG2 (4+), MVLG3 …