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Pharmaceuticals 2011, 4(10), 1381-1399; doi:10.3390/ph4101381

Lipothioureas as Lipids for Gene Transfection: A Review

1, 2, 3, 4, 4, 4 and 4,*
1 UMR 8203, Laboratoire de Vectorologie et Thérapeutiques Anticancéreuses, Université Paris-Sud, 91405 Orsay, CNRS Institut Gustave Roussy, 94805 Villejuif, France 2 Faculté de Pharmacie, Université de Montréal, CP 6128, Succ Centre-Ville, Montréal, QC, H3C 3J7, Canada 3 Commissariat à l’Energie Atomique, Service d’Ingénierie des Protéines, 152, CE-Saclay, 91191 Gif sur Yvette, France 4 UMR 8151 CNRS, U1022 INSERM, Unité de Pharmacologie Chimique et Génétique et d’Imagerie, Université Paris Descartes, Sorbonne Paris Cité, Chimie-ParisTech, 4 avenue de l’observatoire, 75006 Paris, France
* Author to whom correspondence should be addressed.
Received: 1 August 2011 / Revised: 3 October 2011 / Accepted: 11 October 2011 / Published: 24 October 2011
(This article belongs to the Special Issue Gene Therapy)
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Non-viral gene therapy requires innovative strategies to achieve higher transfection efficacy. A few years ago, our group proposed bioinspired lipids whoseinteraction with DNA was not based on ionic interactions, but on hydrogen bonds. We thusdeveloped lipids bearing a thiourea head which allowed an interaction with DNAphosphates through hydrogen bonds. After a proof of concept with a lipid bearing threethiourea functions, a molecular and cellular screening was performed by varying all partsof the lipids: the hydrophobic anchor, the spacer, the linker, and the thiourea head. Twolipothiourea-based structures were identified as highly efficient in vitro transfecting agents.The lipothioureas were shown to reduce non specific interactions with cell membranes anddeliver their DNA content intracellularly more efficiently, as compared to cationiclipoplexes. These lipids could deliver siRNA efficiently and allowed specific cell targetingin vitro. In vivo, thiourea lipoplexes presented a longer retention time in the blood and lessaccumulation in the lungs after an intravenous injection in mice. They also inducedluciferase gene expression in muscle and tumor after local administration in mice.Therefore, these novel lipoplexes represent an excellent alternative to cationic lipoplexes astransfecting agents. In this review we will focus on the structure activity studies thatpermitted the identification of the two most efficient thiourea lipids.
Keywords: lipothiourea; thiourea lipids; DNA; lipoplexes; transfection; gene therapy lipothiourea; thiourea lipids; DNA; lipoplexes; transfection; gene therapy
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Breton, M.; Leblond, J.; Tranchant, I.; Scherman, D.; Bessodes, M.; Herscovici, J.; Mignet, N. Lipothioureas as Lipids for Gene Transfection: A Review. Pharmaceuticals 2011, 4, 1381-1399.

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