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A defective nontransmissible recombinant Sendai virus mediates efficient gene transfer to airway epithelium in vivo

Gene Therapy volume 11, pages 1659–1664 (2004)Cite this article

Abstract

Recombinant Sendai virus (SeV)-mediated gene transfer to differentiated airway epithelial cells has shown to be very efficient, because of its ability to overcome the intra- and extracellular barriers known to limit gene delivery. However, this virus is transmission competent and therefore unlikely to be suitable for use in clinical trials. A nontransmissible, replication-competent recombinant SeV has recently been developed by deleting the envelope Fusion (F) protein gene (SeV/ΔF). Here we show that SeV/ΔF is able to mediate β-galactosidase reporter gene transfer to the respiratory tract of mice in vivo, as well as to human nasal epithelial cells in vitro. Further, in an ex vivo model of differentiated airway epithelium, SeV/ΔF gene transfer was not importantly inhibited by native mucus. When compared to the transmission-competent SeV in vivo, no difference in gene expression was observed at the time of peak expression. The development of an F-defective nontransmissible SeV, which can still efficiently mediate gene transfer to the airway epithelium, represents the first important step towards the use of a cytoplasmic RNA viral vector in clinical trials of gene therapy.

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Acknowledgements

We thank M Festing for his help with statistical analysis. This study was supported by the UK Cystic Fibrosis Trust through a grant to the UK Cystic Fibrosis Gene Therapy Consortium (www.cfgenetherapy.org.uk) and by a Wellcome Trust Senior Clinical Fellowship (EWFWA).

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Authors and Affiliations

  1. Department of Gene Therapy, National Heart & Lung Institute, Imperial College Faculty of Medicine, London, UK

    S Ferrari, U Griesenbach, J Williams, J Zhu, P K Jeffery, D M Geddes & E W F W Alton

  2. DNAVEC Corporation, Tsukuba-city, Ibaraki, Japan

    T Shiraki-Iida, T Shu, T Hironaka, X Hou & M Hasegawa

  3. UK Cystic Fibrosis Gene Therapy Consortium, UK

    S Ferrari, U Griesenbach, D M Geddes & E W F W Alton

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  1. S Ferrari
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  2. U Griesenbach
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  3. T Shiraki-Iida
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Ferrari, S., Griesenbach, U., Shiraki-Iida, T. et al. A defective nontransmissible recombinant Sendai virus mediates efficient gene transfer to airway epithelium in vivo. Gene Ther 11, 1659–1664 (2004). https://doi.org/10.1038/sj.gt.3302334

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