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DNA lipoplexes: Formation of the inverse hexagonal phase observed by coarse-grained molecular dynamics simulation

DNA lipoplexes: Formation of the inverse hexagonal phase observed by coarse-grained molecular dynamics simulation
DNA lipoplexes: Formation of the inverse hexagonal phase observed by coarse-grained molecular dynamics simulation
Mixtures of dsDNA and lipids, so-called lipoplexes, are widely used as less toxic alternatives to viral vectors in transfection studies. However, the transfection efficiency achieved by lipoplexes is significantly lower than that of viral vectors and is a barrier to their use in the clinic. There is now significant evidence suggesting that the molecular organization and structure (nanoarchitecture) of lipoplexes might correlate with biological activity. As a consequence, the ability to predict quantitatively the nanoarchitecture of new systems, and how these might change intracellularly, would be a major tool in the development of rational discovery strategies for more efficient lipoplex formulations. Here we report the use of a coarse-grain molecular dynamics simulation to predict the phases formed by two lipoplex systems: dsDNA?DOPE and dsDNA?DOPE?DOTAP. The predictions of the simulations show excellent agreement with experimental data from polarized light microscopy and small-angle X-ray diffraction (SAXS); the simulations predicted the formation of phases with d-spacings that were comparable to those measured by SAXS. More significantly, the simulations were able to reproduce for the first time the experimentally observed change from a fluid lamellar to an inverse hexagonal phase in the dsDNA?DOPE?DOTAP system as a function of changes in lipid composition. Our studies indicate that coarse-grain MD simulations could provide a powerful tool to understand, and hence design, new lipoplex systems.
0743-7463
12119-12125
Corsi, Josephine
5ff440af-f469-4352-883c-fa6926d8ee2c
Hawtin, Robert W.
b80d12ed-815b-40a8-ae01-f7e2557f4276
Ces, Oscar
3dc0f432-42f3-4308-acc9-e17271c74068
Attard, George S.
3219075d-2364-4f00-aeb9-1d90f8cd0d36
Khalid, Syma
90fbd954-7248-4f47-9525-4d6af9636394
Corsi, Josephine
5ff440af-f469-4352-883c-fa6926d8ee2c
Hawtin, Robert W.
b80d12ed-815b-40a8-ae01-f7e2557f4276
Ces, Oscar
3dc0f432-42f3-4308-acc9-e17271c74068
Attard, George S.
3219075d-2364-4f00-aeb9-1d90f8cd0d36
Khalid, Syma
90fbd954-7248-4f47-9525-4d6af9636394

Corsi, Josephine, Hawtin, Robert W., Ces, Oscar, Attard, George S. and Khalid, Syma (2010) DNA lipoplexes: Formation of the inverse hexagonal phase observed by coarse-grained molecular dynamics simulation. Langmuir, 26 (14), 12119-12125. (doi:10.1021/la101448m). (PMID:20578750)

Record type: Article

Abstract

Mixtures of dsDNA and lipids, so-called lipoplexes, are widely used as less toxic alternatives to viral vectors in transfection studies. However, the transfection efficiency achieved by lipoplexes is significantly lower than that of viral vectors and is a barrier to their use in the clinic. There is now significant evidence suggesting that the molecular organization and structure (nanoarchitecture) of lipoplexes might correlate with biological activity. As a consequence, the ability to predict quantitatively the nanoarchitecture of new systems, and how these might change intracellularly, would be a major tool in the development of rational discovery strategies for more efficient lipoplex formulations. Here we report the use of a coarse-grain molecular dynamics simulation to predict the phases formed by two lipoplex systems: dsDNA?DOPE and dsDNA?DOPE?DOTAP. The predictions of the simulations show excellent agreement with experimental data from polarized light microscopy and small-angle X-ray diffraction (SAXS); the simulations predicted the formation of phases with d-spacings that were comparable to those measured by SAXS. More significantly, the simulations were able to reproduce for the first time the experimentally observed change from a fluid lamellar to an inverse hexagonal phase in the dsDNA?DOPE?DOTAP system as a function of changes in lipid composition. Our studies indicate that coarse-grain MD simulations could provide a powerful tool to understand, and hence design, new lipoplex systems.

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More information

Published date: 28 June 2010

Identifiers

Local EPrints ID: 179199
URI: http://eprints.soton.ac.uk/id/eprint/179199
ISSN: 0743-7463
PURE UUID: b3e0edab-2dee-443f-bc8d-08636ecec8da
ORCID for George S. Attard: ORCID iD orcid.org/0000-0001-8304-0742
ORCID for Syma Khalid: ORCID iD orcid.org/0000-0002-3694-5044

Catalogue record

Date deposited: 31 Mar 2011 11:52
Last modified: 29 Oct 2019 02:07

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