title: Lipophosphonate/lipophosphoramidates: a family of synthetic vectors efficient for gene delivery.
abstract: Lipophophoramidates constitute a class of synthetic vectors which were especially designed for gene delivery. In this family of compounds, the phosphorus functional group links two lipid chains to a spacer ended by a polar headgroup. Such vectors, which can readily be obtained, offer an alternative to the numerous examples of glycerolipid-based vectors that have been more exhaustively studied. Since the pioneering work describing this series of synthetic vectors, several chemical modifications have been proposed with the aim of correlating the molecular structure with the gene transfection efficacy. It has indeed been observed that some modifications which may be considered as minor at first glance, actually have important consequences on both the transfection efficacy and cytotoxic side effects. We herein discuss the modification of the structure of lipophosphoramidates, in particular of their lipidic part and of the nature of the cationic polar head which may be constituted by a trimethylammonium, trimethylphosphonium or trimethylarsonium motif. We also report that, as well as the in vitro transfection efficacy which governs the selection of the most promising vectors for in vivo studies, other aspects related to the synthetic pathway must be also considered for the development of new synthetic vectors (such as modularity of the synthesis, scaling-up).
authors.affiliation: CEMCA, UMR CNRS 6521, IFR148, Université Européenne de Bretagne, Université de Brest, Faculté des Sciences et Techniques, 6 avenue Le Gorgeu, 29238 Brest, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Berchel
authors.forename: Tony
authors.initials: T
authors.lastname: Le Gall
authors.forename: Hélène
authors.initials: H
authors.lastname: Couthon-Gourvès
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Haelters
authors.forename: Tristan
authors.initials: T
authors.lastname: Montier
authors.forename: Patrick
authors.initials: P
authors.lastname: Midoux
authors.forename: Pierre
authors.initials: P
authors.lastname: Lehn
authors.forename: Paul-Alain
authors.initials: PA
authors.lastname: Jaffrès
mesh_terms: D000577:Amides / Q000737:chemistry*; D002412:Cations; D005822:Genetic Vectors; D008055:Lipids / Q000737:chemistry*; D010756:Phosphoric Acids / Q000737:chemistry*; D014162:Transfection
chemical_list: D000577:Amides; D002412:Cations; D008055:Lipids; D010756:Phosphoric Acids; C011067:phosphoramidic acid