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Effective suicide gene therapy in vivo by EBV-based plasmid vector coupled with polyamidoamine dendrimer

Gene Therapy volume 7, pages 53–60 (2000)Cite this article

Abstract

This study demonstrates in vivo effectiveness of a nonviral vector system, Epstein–Barr virus (EBV)-based plasmid vector coupled with polyamidoamine (PAMAM) dendrimer (EBV/polyplex), in suicide gene therapy of cancer. The EBV-based vector is a plasmid vector containing EBV nuclear antigen 1 (EBNA1) gene and oriP from EBV genome. HSV-1 tk gene was transferred into Ewing's sarcoma cell lines, A4573 and KP-EWS-YI, by using an EBV-based plasmid vector, pSES.Tk, or a conventional plasmid vector, pS.Tk. Cells transfected with pSES.Tk/dendrimer showed approximately 100 times lower ID50 to ganciclovir (GCV) compared with those transfected with pS.Tk/dendrimer. Intratumoral injection of pSES.Tk/dendrimer but not pS.Tk/dendrimer drastically suppressed the growth of tumors which had generated from A4573 or Huh7 hepatocellular carcinoma (HCC) cells inoculated into severe combined immunodeficiency (SCID) mice. The treatment with pSES.Tk/dendrimer also resulted in significant prolongation of survival of the mice implanted with A4573. These results suggest that the EBV/polyplex system could be useful for in vivo suicide gene therapy of cancer.

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Acknowledgements

We thank F Hoffmann-La Roche Ltd (Basel, Switzerland) for kindly providing us with GCV. We also thank Ms Satoko Watanabe (Department of Microbiology, Kyoto Prefectural University of Medicine) for her excellent secretarial assistance. This research was supported by a grant-in-aid for scientific research from the Ministry of Education, Science, Sports and Culture, Japan, and the Japan Heart Foundation and IBM Japan Research Grant.

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Authors and Affiliations

  1. Department of Pediatrics, Kyoto Prefectural University of Medicine, Kamikyo, Kyoto, Japan

    H Maruyama-Tabata, T Matsumura, S Hibi & T Sawada

  2. Department of Microbiology, Kyoto Prefectural University of Medicine, Kamikyo, Kyoto, Japan

    H Maruyama-Tabata, Y Harada, E Satoh, F Cui, M Kita, J Imanishi & O Mazda

  3. Department of Third Department of Internal Medicine, Kyoto Prefectural University of Medicine, Kamikyo, Kyoto, Japan

    Y Harada & M Iwai

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  1. H Maruyama-Tabata
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Maruyama-Tabata, H., Harada, Y., Matsumura, T. et al. Effective suicide gene therapy in vivo by EBV-based plasmid vector coupled with polyamidoamine dendrimer. Gene Ther 7, 53–60 (2000). https://doi.org/10.1038/sj.gt.3301044

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