title: DOPC-Detergent Conjugates: Fusogenic Carriers for Improved In Vitro and In Vivo Gene Delivery.
abstract: Phospholipid-detergent conjugates are proposed as fusogenic carriers for gene delivery. Eleven compounds are prepared and their properties are investigated. The ability of the conjugates to promote fusion with a negatively charged model membrane is determined. Their DNA delivery efficiency and cytotoxicity are assessed in vitro. Lipoplexes are administered in the mouse lung, and transgene expression Indeterminate inflammatory activity are measured. The results show that conjugation of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) with C12 E4 produces a carrier that can efficiently deliver DNA to cells, with negligible -associated toxicity. Fusogenicity of the conjugates shows good correlation with in vitro transfection efficiency and crucially depends on the length of the polyether moiety of the detergent. Finally, DOPC-C12 E4 reveals highly potent for in vivo DNA delivery and favorably compares to GL67A, the current golden standard for gene delivery to the airway, opening the way for further promising developments.
authors.affiliation: Laboratoire de Conception et Application de Molécules Bioactives, UMR 7199 CNRS - Université de Strasbourg, Faculté de Pharmacie, 74 route du Rhin - BP 60024, 67401, Illkirch, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Pierrat
authors.affiliation: Laboratoire de Conception et Application de Molécules Bioactives, UMR 7199 CNRS - Université de Strasbourg, Faculté de Pharmacie, 74 route du Rhin - BP 60024, 67401, Illkirch, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Casset
authors.affiliation: Laboratoire de Conception et Application de Molécules Bioactives, UMR 7199 CNRS - Université de Strasbourg, Faculté de Pharmacie, 74 route du Rhin - BP 60024, 67401, Illkirch, France.
authors.forename: Dimitri
authors.initials: D
authors.lastname: Kereselidze
authors.affiliation: Laboratoire de Conception et Application de Molécules Bioactives, UMR 7199 CNRS - Université de Strasbourg, Faculté de Pharmacie, 74 route du Rhin - BP 60024, 67401, Illkirch, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Lux
authors.affiliation: Laboratoire de Conception et Application de Molécules Bioactives, UMR 7199 CNRS - Université de Strasbourg, Faculté de Pharmacie, 74 route du Rhin - BP 60024, 67401, Illkirch, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Pons
authors.affiliation: Laboratoire de Conception et Application de Molécules Bioactives, UMR 7199 CNRS - Université de Strasbourg, Faculté de Pharmacie, 74 route du Rhin - BP 60024, 67401, Illkirch, France.
authors.forename: Luc
authors.initials: L
authors.lastname: Lebeau
mesh_terms: D000818:Animals; D004247:DNA / Q000737:chemistry* / Q000494:pharmacology; D003902:Detergents / Q000737:chemistry; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D051379:Mice; D010316:Particle Size; D010713:Phosphatidylcholines / Q000737:chemistry* / Q000494:pharmacology; D010743:Phospholipids / Q000737:chemistry / Q000494:pharmacology; D014162:Transfection; D019076:Transgenes / Q000235:genetics
chemical_list: D003902:Detergents; D010713:Phosphatidylcholines; D010743:Phospholipids; D004247:DNA; C017251:1,2-oleoylphosphatidylcholine
keywords: cationic lipid; drug delivery systems; gene delivery; lung transfection; nanomedicine