STRUCTURE OF DNA-CATIONIC LIPOSOME COMPLEXES - DNA INTERCALATION IN MULTILAMELLAR MEMBRANES IN DISTINCT INTERHELICAL PACKING REGIMES

Cationic liposomes complexed with DNA (CL-DNA) are promising synthetic ally based nonviral carriers of DNA vectors for gene therapy. The solu tion structure of CL-DNA complexes was probed on length scales from su bnanometer to micrometer by synchrotron x-ray diffraction and optical microscopy. The addition of either linear lambda-phage or plasmid DNA to CLs resulted in an unexpected topological transition from liposomes to optically birefringent liquid-crystalline condensed globules. X-ra y diffraction of the globules revealed a novel multilamellar structure with alternating lipid bilayer and DNA monolayers. The lambda-DNA cha ins form a one-dimensional lattice with distinct interhelical packing regimes. Remarkably, in the isoelectric point regime, the lambda-DNA i nteraxial spacing expands between 24.5 and 57.1 angstroms upon lipid d ilution and is indicative of a long-range electrostatic-induced repuls ion that is possibly enhanced by chain undulations.