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).
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Acknowledgements
We would like to acknowledge the excellent technical help of J Kintz, M de Meyer, H Schultz, F Mischler, D Elmlinger, C Mougin, V Nourtier, C Gerard and N Settelen; Dr B Cavallini and I Renardet for preparation of plasmid DNA. We thank Dr M Courtney for critical comments on the manuscript and M Autem for help with the statistical analysis. Clodronate was a gift from Boehringer Mannheim GmbH, Mannheim, Germany. We also thank Drs D Heissler and A Nazih (ULP Strasbourg) for the synthesis of cationic glycerolipids and Drs MA Zanta and JP Behr for providing plasmid pCMV-Luc.
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Schughart, K., Bischoff, R., Hadji, D. et al. Effect of liposome-encapsulated clodronate pretreatment on synthetic vector-mediated gene expression in mice. Gene Ther 6, 448–453 (1999). https://doi.org/10.1038/sj.gt.3300826
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DOI: https://doi.org/10.1038/sj.gt.3300826
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