AN INVERTED HEXAGONAL PHASE OF CATIONIC LIPOSOME-DNA COMPLEXES RELATED TO DNA RELEASE AND DELIVERY

A two-dimensional columnar phase in mixtures of DNA complexed with cat ionic liposomes has been found in the Lipid composition regime known t o be significantly more efficient at transfecting mammalian cells in c ulture compared to the lamellar (L-alpha(subset of)) structure of cati onic liposome-DNA complexes. The structure, derived from synchrotron x -ray diffraction, consists of DNA coated by cationic lipid monolayers and arranged on a two-dimensional hexagonal lattice (H-parallel to(sub set of)). Two membrane-altering pathways induce the L-alpha(subset of) --> H-parallel to(subset of) transition: one where the spontaneous cu rvature of the Lipid monolayer is driven negative, and another where t he membrane bending rigidity is lowered with a new class of helper-lip ids. Optical microscopy revealed that the L-alpha(subset of) complexes bind stably to anionic vesicles (models of cellular membranes), where as the more transfectant H-parallel to(subset of) complexes are unstab le and rapidly fuse and release DNA upon adhering to anionic vesicles.