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 synthetically based nonviral carriers of DNA vectors for gene therapy. The solution structure of CL-DNA complexes was probed on length scales from subnanometer to micrometer by synchrotron x-ray diffraction and optical microscopy. The addi...

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Published inScience (American Association for the Advancement of Science) Vol. 275; no. 5301; pp. 810 - 814
Main Authors Rädler, Joachim O., Koltover, Ilya, Salditt, Tim, Safinya, Cyrus R.
Format Journal Article
LanguageEnglish
Published United States American Society for the Advancement of Science 07.02.1997
American Association for the Advancement of Science
The American Association for the Advancement of Science
Subjects
Bacteriophage lambda
Biochemistry
Cations
Chemical Phenomena
Chemistry, Physical
Deoxyribonucleic acid
DNA
DNA - chemistry
DNA, Viral - chemistry
Fatty Acids, Monounsaturated
Gene therapy
Genetic vectors
Globules
Isoelectric Point
Light
Lipid Bilayers
Lipids
Liposomes
Membranes
Microscopy, Fluorescence
Microscopy, Interference
Molecules
Nucleic Acid Conformation
Phosphatidylcholines
Phosphatidylethanolamines
Plasmids
Quaternary Ammonium Compounds
Scattering, Radiation
Synchrotrons
Transfection
X-Ray Diffraction
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Summary:Cationic liposomes complexed with DNA (CL-DNA) are promising synthetically based nonviral carriers of DNA vectors for gene therapy. The solution structure of CL-DNA complexes was probed on length scales from subnanometer to micrometer by synchrotron x-ray diffraction and optical microscopy. The addition of either linear λ-phage or plasmid DNA to CLs resulted in an unexpected topological transition from liposomes to optically birefringent liquid-crystalline condensed globules. X-ray diffraction of the globules revealed a novel multilamellar structure with alternating lipid bilayer and DNA monolayers. The λ-DNA chains form a one-dimensional lattice with distinct interhelical packing regimes. Remarkably, in the isoelectric point regime, the λ-DNA interaxial spacing expands between 24.5 and 57.1 angstroms upon lipid dilution and is indicative of a long-range electrostatic-induced repulsion that is possibly enhanced by chain undulations.
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ISSN:0036-8075
1095-9203
DOI:10.1126/science.275.5301.810