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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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References

  1. Blaese RM et al. T lymphocyte-directed gene therapy for ADA-SCID: initial trial results after 4 years. Science 1995; 270: 475–480.

    Article  CAS  PubMed  Google Scholar 

  2. Altenschmidt U, Moritz D, Groner B . Specific cytotoxic T lymphocytes in gene therapy. J Mol Med 1997; 75: 259–266.

    Article  CAS  PubMed  Google Scholar 

  3. Misaki Y et al. Gene-transferred oligoclonal T cells predominantly persist in peripheral blood from an adenosine deaminase-deficient patient during gene therapy. Mol Ther 2001; 3: 24–27.

    Article  CAS  PubMed  Google Scholar 

  4. Lam JS et al. Improved gene transfer into human lymphocytes using retroviruses with the gibbon ape leukemia virus envelope. Hum Gene Ther 1996; 7: 1415–1422.

    Article  CAS  PubMed  Google Scholar 

  5. Pollok KE et al. High-efficiency gene transfer into normal and adenosine deaminase-deficient T lymphocytes is mediated by transduction on recombinant fibronectin fragments. J Virol 1998; 72: 4882–4892.

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Ayuk F et al. Establishment of an optimised gene transfer protocol for human primary T lymphocytes according to clinical requirements. Gene Therapy 1999; 6: 1788–1792.

    Article  CAS  PubMed  Google Scholar 

  7. Movassagh M et al. Retrovirus-mediated gene transfer into T cells: 95% transduction efficiency without further in vitro selection. Hum Gene Ther 2000; 11: 1189–1200.

    Article  CAS  PubMed  Google Scholar 

  8. Kuhlcke K et al. Highly efficient retroviral gene transfer based on centrifugation-mediated vector preloading of tissue culture vessels. Mol Ther 2002; 5: 473–478.

    Article  CAS  PubMed  Google Scholar 

  9. Hege KM, Roberts MR . T-cell gene therapy. Curr Opin Biotechnol 1996; 7: 629–634.

    Article  CAS  PubMed  Google Scholar 

  10. Tuohy VK, Mathisen PM . T cell design for therapy in autoimmune demyelinating disease. J Neuroimmunol 2000; 107: 226–232.

    Article  CAS  PubMed  Google Scholar 

  11. Rosenberg SA et al. Gene transfer into humans – immunotherapy of patients with advanced melanoma, using tumor-infiltrating lymphocytes modified by retroviral gene transduction. N Engl J Med 1990; 323: 570–578.

    Article  CAS  PubMed  Google Scholar 

  12. Dardalhon V et al. Lentivirus-mediated gene transfer in primary T cells is enhanced by a central DNA flap. Gene Therapy 2001; 8: 190–198.

    Article  CAS  PubMed  Google Scholar 

  13. Buchschacher Jr GL, Wong-Staal F . Development of lentiviral vectors for gene therapy for human diseases. Blood 2000; 95: 2499–2504.

    CAS  PubMed  Google Scholar 

  14. Lamb RA, Kolakofsky D . Paramyxoviridae: the viruses and their replication. In: Fields BN, Howley PM et al (eds). Fields of Virology. Lippincott-Raven Publishers: Philadelphia, 1996, pp 1177–1204.

    Google Scholar 

  15. Collins PL, Chanock RM, Mclntosh K . Parainfluenza viruses. In: Fields BN, Howley PM et al (eds). Fields of Virology. Lippincott-Raven Publisher: Philadelphia, 1996, pp. 1205–1241.

    Google Scholar 

  16. Kumar M, Hassan MQ, Tyagi SK, Sarkar DP . A 45,000-M(r) glycoprotein in the Sendai virus envelope triggers virus-cell fusion. J Virol 1997; 71: 6398–6406.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Eguchi A et al. Identification and characterization of cell lines with a defect in a post-adsorption stage of Sendai virus-mediated membrane fusion. J Biol Chem 2000; 275: 17549–17555.

    Article  CAS  PubMed  Google Scholar 

  18. Glezen WP, Denny FW . Parainfluenza virus. In: Evans AS, Kaslow RA (eds). Viral Infection of Humans. Plenum Medical Book Company: New York, 1997, pp 551–567.

    Chapter  Google Scholar 

  19. Li HO et al. A cytoplasmic RNA vector derived from nontransmissible Sendai virus with efficient gene transfer and expression. J Virol 2000; 74: 6564–6569.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Yonemitsu Y et al. Efficient gene transfer to airway epithelium using recombinant Sendai virus. Nat Biotechnol 2000; 18: 970–973.

    Article  CAS  PubMed  Google Scholar 

  21. Masaki I et al. Recombinant Sendai virus-mediated gene transfer to vasculature: a new class of efficient gene transfer vector to the vascular system. FASEB J 2001; 15: 1294–1296.

    Article  CAS  PubMed  Google Scholar 

  22. Masaki I et al. Angiogenic gene therapy for experimental critical limb ischemia: acceleration of limb loss by overexpression of vascular endothelial growth factor 165 but not of fibroblast growth factor-2. Circ Res 2002; 90: 966–973.

    Article  CAS  PubMed  Google Scholar 

  23. Yamashita A et al. Fibroblast growth factor-2 determines severity of joint disease in adjuvant-induced arthritis in rats. J Immunol 2002; 168: 450–457.

    Article  CAS  PubMed  Google Scholar 

  24. Ikeda Y et al. Recombinant sendai virus-mediated gene transfer into adult rat retinal tissue: efficient gene transfer by brief exposure. Exp Eye Res 2002; 75: 39–48.

    Article  CAS  PubMed  Google Scholar 

  25. Shiotani A et al. Skeletal muscle regeneration after insulin-like growth factor I gene transfer by recombinant Sendai virus vector. Gene Therapy 2001; 8: 1043–1050.

    Article  CAS  PubMed  Google Scholar 

  26. Moyer SA, Baker SC, Lessard JL . Tubulin: a factor necessary for the synthesis of both Sendai virus and vesicular stomatitis virus RNAs. Proc Natl Acad Sci USA 1986; 83: 5405–5409.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Sha WC et al. Selective expression of an antigen receptor on CD8-bearing T lymphocytes in transgenic mice. Nature 1988; 335: 271–274.

    Article  CAS  PubMed  Google Scholar 

  28. Markwell MA, Paulson JC . Sendai virus utilizes specific sialyloligosaccharides as host cell receptor determinants. Proc Natl Acad Sci USA 1980; 77: 5693–5697.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Okada Y, Tadokoro J . The distribution of cell fusion capacity among several cell strains or cells caused by HVJ. Exp Cell Res 1963; 32: 417–430.

    Article  CAS  PubMed  Google Scholar 

  30. Bunnell BA et al. High-efficiency retroviral-mediated gene transfer into human and nonhuman primate peripheral blood lymphocytes. Proc Natl Acad Sci USA 1995; 92: 7739–7743.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Chuck AS, Palsson BO . Consistent and high rates of gene transfer can be obtained using flow-through transduction over a wide range of retroviral titers. Hum Gene Ther 1996; 7: 743–750.

    Article  CAS  PubMed  Google Scholar 

  32. Chinnasamy D et al. Lentiviral-mediated gene transfer into human lymphocytes: role of HIV-1 accessory proteins. Blood 2000; 96: 1309–1316.

    CAS  PubMed  Google Scholar 

  33. Fehse B et al. Highly-efficient gene transfer with retroviral vectors into human T lymphocytes on fibronectin. Br J Haematol 1998; 102: 566–574.

    Article  CAS  PubMed  Google Scholar 

  34. Watts TH, DeBenedette MA . T cell co-stimulatory molecules other than CD28. Curr Opin Immunol 1999; 11: 286–293.

    Article  CAS  PubMed  Google Scholar 

  35. Kato A et al. Y2, the smallest of the Sendai virus C proteins, is fully capable of both counteracting the antiviral action of interferons and inhibiting viral RNA synthesis. J Virol 2001; 75: 3802–3810.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Biron CA, Sen GC . Interferons and other cytokine. In: Fields BN, Howley PM et al (eds). Fields of Virology. Lippincott-Raven Publishers: Philadelphia, 1996, pp 321–351.

    Google Scholar 

  37. Maus MV et al. Ex vivo expansion of polyclonal and antigen-specific cytotoxic T lymphocytes by artificial APCs expressing ligands for the T-cell receptor, CD28 and 4-1BB. Nat Biotechnol 2002; 20: 143–148.

    Article  CAS  PubMed  Google Scholar 

  38. Kato A et al. Initiation of Sendai virus multiplication from transfected cDNA or RNA with negative or positive sense. Genes Cells 1996; 1: 569–579.

    Article  CAS  PubMed  Google Scholar 

  39. Sakai Y et al. Accommodation of foreign genes into the Sendai virus genome: sizes of inserted genes and viral replication. FEBS Lett 1999; 456: 221–226.

    Article  CAS  PubMed  Google Scholar 

  40. Kolakofsky D et al. Paramyxovirus RNA synthesis and the requirement for hexamer genome length: the rule of six revisited. J Virol 1998; 72: 891–899.

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Fuerst TR, Niles EG, Studier FW, Moss B . Eukaryotic transient-expression system based on recombinant vaccinia virus that synthesizes bacteriophage T7 RNA polymerase. Proc Natl Acad Sci USA 1986; 83: 8122–8126.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Yonemitsu Y, Kaneda Y . Hemagglutinating virus of japan liposome-mediated gene delivery to vascular cells. In: Baker AH (ed). Vascular Disease: Molecular Biology and Gene Therapy Protocols. Humana Press: Totowa, NJ, 1999, pp 295–306.

    Chapter  Google Scholar 

  43. Picker LJ et al. Control of lymphocyte recirculation in man. I. Differential regulation of the peripheral lymph node homing receptor L-selection on T cells during the virgin to memory cell transition. J Immunol 1993; 150: 1105–1121.

    CAS  PubMed  Google Scholar 

  44. Ostrowski MA et al. Both memory and CD45RA+/CD62L+ naive CD4(+) T cells are infected in human immunodeficiency virus type 1-infected individuals. J Virol 1999; 73: 6430–6435.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Jin CH et al. Recombinant Sendai virus provides a highly efficient gene transfer into human cord blood-derived hematopoietic stem cells. Gene Therapy 10: 272–277.

    Article  CAS  PubMed  Google Scholar 

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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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