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Intraperitoneal linear polyethylenimine (L-PEI)-mediated gene delivery to ovarian carcinoma nodes in mice

Cancer Gene Therapy volume 13, pages 367–374 (2006)Cite this article

Abstract

Linear polyethylenimine (L-PEI) is an efficient transfection agent for ovarian carcinoma cells in vitro and ex vivo. In the present work, we go a step further and evaluate the efficacy of L-PEI in human ovarian tumor nodes developed in mice. PEI/DNA complexes were administered intraperitoneally instead of intravenously to avoid sequestering of complexes in the lung and liver and to allow transfection of nonvascularized tumor nodes. Plasmid biodistribution was studied by PCR and gene expression was characterized using complementary luciferase and β-galactosidase assays. Intraperitoneal (i.p.) injection of L-PEI/DNA complexes allowed the straightforward distribution of plasmid in the whole peritoneal cavity. Gene expression occurred in many organs, but tumor nodes appeared as preferential sites for transgene expression. The i.p. delivery route allowed repeated injections and administration of large amounts of DNA (up to 400 μg) without signs of toxicity, even for doses well beyond the intravenous lethal dose. Transgene expression was dose-dependent and transient. However, multiple injections allowed its persistence to increase. These results provide encouraging elements towards the development of PEI-based gene therapy protocols for the treatment of advanced stage ovarian carcinoma.

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Acknowledgements

We thank M-C Bon for the technical assistance in animal care, and Dr J-F Héron, Dr H Crouet and Dr F Joly, clinicians of the F Baclesse Cancer Center, for their constant support and their active participation in the field of the development of innovative therapeutics in the ovarian cancer work group. This work was supported by the ‘Ligue Contre le Cancer’ (Comités du Calvados et de l'Orne), the ‘Association pour la Recherche contre le Cancer’ (ARC), The Association ‘Cœur et Cancer’ (Cherbourg, France), the ‘Conseil Régional de Basse-Normandie’, the French State, the European Community (Fonds Européens pour le Développement de la Recherche–FEDER) and the ‘Agence Nationale de Valorisation de la Recherche’ (ANVAR).

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Authors and Affiliations

  1. Groupe Régional d'Etude sur le Cancer (GRECAN), Unité ‘Biologie et Thérapies Innovantes des Cancers Localement Agressifs’ et, Centre F. Baclesse, Caen, cedex, France

    M-H Louis, S Dutoit, E Deslandes, P Gauduchon & L Poulain

  2. Laboratoire d'Anatomie Pathologique, Centre de Lutte Contre le Cancer F.Baclesse, Caen, cedex, France

    Y Denoux

  3. PolyPlus-Transfection SAS BP 90018, Illkirch, cedex, France

    P Erbacher

  4. Laboratoire de Chimie Génétique, CNRS UMR 7514, Faculté de Pharmacie de Strasbourg, Illkirch, France

    J-P Behr

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  1. M-H Louis
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Correspondence to L Poulain.

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Louis, MH., Dutoit, S., Denoux, Y. et al. Intraperitoneal linear polyethylenimine (L-PEI)-mediated gene delivery to ovarian carcinoma nodes in mice. Cancer Gene Ther 13, 367–374 (2006). https://doi.org/10.1038/sj.cgt.7700893

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