Recombinant Sendai virus vectors for activated T lymphocytes

S. Okano, Y. Yonemitsu, S. Nagata, S. Sata, M. Onimaru, K. Nakagawa, Y. Tomita, K. Kishihara, S. Hashimoto, Y. Nakashima, K. Sugimachi, M. Hasegawa, K. Sueishi

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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.

Original languageEnglish
Pages (from-to)1381-1391
Number of pages11
JournalGene Therapy
Volume10
Issue number16
DOIs
Publication statusPublished - Aug 1 2003

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All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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