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

Gene Therapy volume 6, pages 448–453 (1999)Cite this article

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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Authors and Affiliations

  1. Department of Molecular and Cellular Biology and Department of Biochemistry, TRANSGENE SA, Strasbourg, France

    K Schughart, D Ali Hadji, O Boussif, F Perraud, N Accart, U B Rasmussen, A Pavirani & H V J Kolbe

  2. Department of Bioanalytical Chemistry, Astra-Draco AB, Lund, Sweden

    R Bischoff

  3. Department of Cell Biology and Immunology, Vrije Universiteit, Amsterdam, The Netherlands

    N van Rooijen

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  1. K Schughart
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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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