Chiral DNA packaging in DNA‐cationic liposome assemblies

Abstract
Recent studies have indicated that the structural features of DNA‐lipid assemblies, dictated by the lipid composition and cationic lipid‐to‐DNA ratio, critically affect the efficiency of these complexes in acting as vehicles for cellular delivery of genetic material. Using circular dichroism we find that upon binding DNA, positively‐charged liposomes induce a secondary conformational transition of the DNA molecules from the native B form to the C motif. Liposomes composed of positively‐charged and neutral ‘helper’ lipids, found to be particularly effective as transfecting agents, induce – in addition to secondary conformational changes – DNA condensation into a left‐handed cholesteric‐like phase. A structural model is presented according to which two distinct, yet inter‐related modes of DNA packaging coexist within such assemblies. The results underline the notion that subtle changes in the components of a supramolecular assembly may substantially modulate the interplay of interactions which dictate its structure and functional properties.

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