title: Effect of liposome-encapsulated clodronate pretreatment on synthetic vector-mediated gene expression in mice.
abstract: One of the main limitations for the use of synthetic vectors in gene therapy is their relatively low in vivo efficiency when compared with viral vectors. Here, we describe a pretreatment protocol with liposome-encapsulated clodronate in mice by which gene expression levels of a luciferase reporter gene could be increased up to nine-fold in the lung, after intravenous (i.v.) injection of glycerolipoplexes. Optimal results were obtained if mice were pretreated with liposome-encapsulated clodronate 1 day before injection of lipoplexes. The enhancement effect could be observed for lipoplexes prepared with different multivalent cationic glycerolipids. Most remarkably, polyplexes behaved in the opposite way. Liposome-encapsulated clodronate pretreatment strongly reduced reporter gene expression after i.v. injection of polyethylenimine-polyplexes (ExGen500).
authors.affiliation: Department of Molecular and Cellular Biology, TRANSGENE SA, Strasbourg, France.
authors.forename: K
authors.initials: K
authors.lastname: Schughart
authors.forename: R
authors.initials: R
authors.lastname: Bischoff
authors.forename: D A
authors.initials: DA
authors.lastname: Hadji
authors.forename: O
authors.initials: O
authors.lastname: Boussif
authors.forename: F
authors.initials: F
authors.lastname: Perraud
authors.forename: N
authors.initials: N
authors.lastname: Accart
authors.forename: U B
authors.initials: UB
authors.lastname: Rasmussen
authors.forename: A
authors.initials: A
authors.lastname: Pavirani
authors.forename: N
authors.initials: N
authors.lastname: van Rooijen
authors.forename: H V
authors.initials: HV
authors.lastname: Kolbe
mesh_terms: D000818:Animals; D004002:Clodronic Acid / Q000008:administration & dosage*; D015870:Gene Expression; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D005990:Glycerol; D007275:Injections, Intravenous; D008081:Liposomes; D008156:Luciferases / Q000235:genetics; D008168:Lung / Q000378:metabolism*; D051379:Mice; D011094:Polyethyleneimine
chemical_list: D008081:Liposomes; D004002:Clodronic Acid; D011094:Polyethyleneimine; D008156:Luciferases; D005990:Glycerol