Effect of liposome-encapsulated clodronate pretreatment on synthetic vector-mediated gene expression in mice

One of the main limitations for the use of synthetic vectors in gene therap y is their relatively low in vivo efficiency when compared with viral vecto rs. Here, we describe a pretreatment protocol with liposome-encapsulated cl odronate in mice by which gene expression levels of a luciferase reporter g ene could be increased up to nine-fold in the lung, after intravenous (i.v. ) injection of glycerolipoplexes. Optimal results were obtained if mice wer e pretreated with liposome-encapsulated clodronate 1 day before injection o f lipoplexes. The enhancement effect could be observed for lipoplexes prepa red with different multivalent cationic glycerolipids. Most remarkably, pol yplexes behaved in the opposite way. Liposome-encapsulated clodronate pretr eatment strongly reduced reporter gene expression after i.v. injection of p olyethylenimine-polyplexes (ExGen500).