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Why Is Less Cationic Lipid Required To Prepare Lipoplexes from Plasmid DNA than Linear DNA in Gene Therapy?

Munoz-Ubeda, Monica and Misra, Santosh K and Barran-Berdon, Ana L and Aicart-Ramos, Clara and Sierra, Maria B and Biswas, Joydeep and Kondaiah, Paturu and Junquera, Elena and Bhattacharya, Santanu and Aicart, Emilio (2011) Why Is Less Cationic Lipid Required To Prepare Lipoplexes from Plasmid DNA than Linear DNA in Gene Therapy? In: Journal of the American Chemical Society, 133 (45). pp. 18014-18017.

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Official URL: http://pubs.acs.org/doi/abs/10.1021/ja204693f

Abstract

The most important objective of the present study was to explain why cationic lipid (CL)-mediated delivery of plasmid DNA (pDNA) is better than that of linear DNA in gene therapy, a question that, until now, has remained unanswered. Herein for the first time we experimentally show that for different types of CLs, pDNA, in contrast to linear DNA, is compacted with a large amount of its counterions, yielding a lower effective negative charge. This feature has been confirmed through a number of physicochemical and biochemical investigations. This is significant for both in vitro and in vivo transfection studies. For an effective DNA transfection, the lower the amount of the CL, the lower is the cytotoxicity. The study also points out that it is absolutely necessary to consider both effective charge ratios between CL and pDNA and effective pDNA charges, which can be determined from physicochemical experiments.

Item Type: Journal Article
Additional Information: Copyright of this article belongs to American Chemical Society.
Department/Centre: Division of Biological Sciences > Molecular Reproduction, Development & Genetics (formed by the merger of DBGL and CRBME)
Division of Chemical Sciences > Organic Chemistry
Date Deposited: 23 Dec 2011 11:37
Last Modified: 23 Dec 2011 11:37
URI: http://eprints.iisc.ernet.in/id/eprint/42847

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