NDLI: Structural characteristics of supramolecular assemblies formed by guanidinium-cholesterol reagents for gene transfection.

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Structural characteristics of supramolecular assemblies formed by guanidinium-cholesterol reagents for gene transfection.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Hauchecorne, M. Crouzet, J. Scherman, D. Toury, R. Lehn, J. M. Lehn, P. Vigneron, J. P. Ramasawmy, R. Oudrhiri, N. Airiau, M. Pitard, B. Aguerre, O.
Description	Author Affiliation: Pitard B ( Unité Mixte de Recherche, 133 Rhône-Poulenc Rorer, Centre National de la Recherche Scientifique, France. bruno.pitard@rp-rorer.fr);
Abstract	We have recently discovered that cationic cholesterol derivatives characterized by guanidinium polar headgroups are very efficient for gene transfection in vitro and in vivo. In spite of being based on some rationale at the molecular level, the development of these new synthetic vectors was nevertheless empirical. Indeed, the factors and processes underlying cationic lipid-mediated gene transfer are still poorly understood. Thus, to get a better insight into the mechanisms involved, we have examined the supramolecular structure of lipid/DNA aggregates obtained when using reagent bis(guanidinium)-tren-cholesterol (BGTC), either alone or as a liposomal formulation with the neutral phospholipid dioleoyl phosphatidylethanolamine (DOPE). We here report the results of cryotransmission electron microscopy studies and small-angle x-ray scattering experiments, indicating the presence of multilamellar domains with a regular spacing of 70 A and 68 A in BGTC/DOPE-DNA and BGTC-DNA aggregates, respectively. In addition, DNA lipoplexes with similar lamellar patterns were detected inside transfected HeLa cells by conventional transmission electron microscopy. These results suggest that DNA condensation by multivalent guanidinium-cholesterol cationic lipids involves the formation of highly ordered multilamellar domains, the DNA molecules being intercalated between the lipid bilayers. These results also invite further investigation of the intracellular fate of the internalized lipid/DNA structures during their trafficking toward the cell nucleus. The identification of the basic features of active complexes should indeed help in the design of improved guanidinium-based vectors.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	6
Volume Number	96
Language	English
Publisher	National Academy of Sciences
Publisher Date	1999-05-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Cholesterol Chemistry DNA Gene Transfer Techniques Genetic Vectors Guanidine Ultrastructure HeLa Cells Microscopy, Electron X-Ray Diffraction Research Support, Non-U.S. Gov't Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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