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Lipoplexes with alkylphospholipid as new helper lipid for efficient in vitro and in vivo gene transfer in tumor therapy

Cancer Gene Therapy volume 10, pages 302–311 (2003)Cite this article

Abstract

To improve liposomal gene transfer we investigated the influence of membrane-interacting alkylphospholipids (APLs) on gene transfer efficiency in vitro and in vivo using the LacZ reporter gene and the cytosine deaminase (CD) suicide gene. Liposomes were first optimized concerning the kind and amount of APL and the additional liposome components. Thus, an up to 270% increase in the transfer efficiency of the LacZ gene into HCT15 and HCT116 human colon carcinoma cells could be obtained in vitro compared to lipofectin-mediated transfection by using a lipoplex consisting of tetradecylphosphocholine/dimethyldioctadecylamine/cholesterol/dioleylphosphoethanolamine-liposomes and the pSV40-βGal-plasmid. The in vivo experiments revealed that alkylphospholipid-lipoplexes (APL–LPs) were similarly effective in the transfer of the LacZ gene into colon carcinoma as formulations consisting of lipofectin. Using the CD-gene in combination with APL-LPs resulted in a significantly stronger inhibition of C26 colon carcinoma growth compared to lipofectin-mediated gene transfer following treatment of mice with the prodrug 5-fluorocytosine. The results of this study demonstrate for the first time that the utilization of membrane-active APLs as component of the liposomal part of lipoplexes enhances the efficacy of gene therapy in vitro and in vivo.

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Acknowledgements

The technical skills of AD Teppke and L Malcherek are gratefully acknowledged. We thank M Lemm and M Becker for performing the animal experiments. We further thank G Nöβner and P Hilgard from ASTA Medica for generously providing the alkylphospholipids and W. Uckert for kindly providing the pCMV/CD-1 Plasmid.

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Author notes

  1. Angelika Ress

    Present address: Institute of Medical Virology, University of Zurich, Zurich, Switzerland

Authors and Affiliations

  1. Max-Delbrück-Center for Molecular Medicine, Berlin, Germany

    Reinhard Zeisig, Angelika Ress, Iduna Fichtner & Wolfgang Walther

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  1. Reinhard Zeisig
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Correspondence to Reinhard Zeisig.

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Zeisig, R., Ress, A., Fichtner, I. et al. Lipoplexes with alkylphospholipid as new helper lipid for efficient in vitro and in vivo gene transfer in tumor therapy. Cancer Gene Ther 10, 302–311 (2003). https://doi.org/10.1038/sj.cgt.7700572

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