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Recombinant Sendai virus provides a highly efficient gene transfer into human cord blood-derived hematopoietic stem cells

Gene Therapy volume 10, pages 272–277 (2003)Cite this article

Abstract

Hematopoietic stem cells (HSCs) are a promising target for gene therapy, however, the low efficiencies of gene transfer using currently available vectors face practical limitations. We have recently developed a novel and efficient gene transfer agent, namely recombinant Sendai virus (SeV), and we have here characterized SeV-mediated gene transfer to human cord blood (CB) HSCs and primitive progenitor cells (PPC) using the jelly fish green fluorescent protein (GFP) gene. Even at a relatively low titer (10 multiplicity of infections), SeV achieved highly efficient GFP expression in CB CD34+ cells (85.5±5.8%), as well as more immature CB progenitor cells, CD34+AC133+ (88.2±3.7%) and CD34+CD38− (84.6±5.7%) cells, without cytokines prestimulation, that was a clear contrast to the features of gene transfer using retroviruses. SeV-mediated gene transfer was not seriously affected by the cell cycle status. In vitro cell differentiation studies revealed that gene transfer occurred in progenitor cells of all lineages (GM-CFU, 73.0±11.1%; BFU-E, 24.7±4.0%; Mix-CFU, 59±4.0%; and total, 50.0±7.0%). These findings show that SeV could prove to be a promising vector for efficient gene transfer to CB HSCs, while preserving their ability to reconstitute the entire hematopoietic series.

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Acknowledgements

We thank Dr Kusuo Sanada for providing cord blood samples. This study was supported by a Grant of Promotion of Basic Scientific Research in Medical Frontier of the Organization for Pharmaceutical Safety and Research, and by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan. M Ohara provided language assistance.

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Authors and Affiliations

  1. Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    C H Jin, K Kusuhara, A Nomura & T Hara

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

    Y Yonemitsu, S Okano, H Takeshita & K Sueishi

  3. DNAVEC Research Inc. Tsukuba, Ibaraki, Japan

    M Hasegawa

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  1. C H Jin
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Jin, C., Kusuhara, K., Yonemitsu, Y. et al. Recombinant Sendai virus provides a highly efficient gene transfer into human cord blood-derived hematopoietic stem cells. Gene Ther 10, 272–277 (2003). https://doi.org/10.1038/sj.gt.3301877

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