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Recombinant Sendai virus vectors for activated T lymphocytes

Gene Therapy volume 10, pages 1381–1391 (2003)Cite this article

Abstract

T-lymphocyte-directed gene therapy has potential as a treatment of subjects with immunological disorders. One current limitation of this therapeutic strategy is low gene transfer efficiency, even when complex procedures are used. We report herein that a recombinant Sendai virus vector (SeV) was able to overcome this issue. Using jellyfish enhanced green fluorescent protein gene (EGFP), we found that SeV was able to transduce and express a foreign gene specifically and efficiently in activated murine and human T cells, but not in naive T cells, without centrifugation or reagents including polybrene and protamine sulfate; the present findings were in clear contrast to those demonstrated with the use of retroviruses. The transduction was selective in antigen-activated T cells, while antigen-irrelevant T cells were not transduced, even under bystander activation from specific T-cell responses by antigens ex vivo. Receptor saturation studies suggested a possible mechanism of activated T-cell-specific gene transfer, ie, SeV might attach to naive T cells but might be unable to enter their cytoplasm. We therefore propose that the SeV vector system may prove to be a potentially important alternative in the area of T-cell-directed gene therapy used in the clinical setting.

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Acknowledgements

We thank Dr Onoe for kindly providing the 2C transgenic mice and M Ohara for providing editorial services.

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Authors and Affiliations

  1. Division of Pathophygiological and Experimental Pathology, Department of Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    S Okano, Y Yonemitsu, S Nagata, S Sata, M Onimaru, K Nakagawa, S Hashimoto, Y Nakashima & K Sueishi

  2. Department of Cardiovascular Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Y Tomita

  3. Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    K Sugimachi

  4. Division of Molecular and Cellular Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan

    K Kishihara

  5. DNAVEC Research Inc., Tsukuba-city, Ibaraki, Japan

    M Hasegawa

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This work was supported by a Grant for the Promotion of Basic Scientific Research in the Medical Frontier of The Organization for Pharmaceutical Safety and Research

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Okano, S., Yonemitsu, Y., Nagata, S. et al. Recombinant Sendai virus vectors for activated T lymphocytes. Gene Ther 10, 1381–1391 (2003). https://doi.org/10.1038/sj.gt.3301998

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Keywords

  • gene therapy
  • T cells
  • Sendai virus vector
  • enhanced green fluorescent protein gene

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