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In vivo episomal maintenance of a herpesvirus saimiri-based gene delivery vector

Gene Therapy volume 8, pages 1762–1769 (2001)Cite this article

Abstract

Herpesvirus saimiri (HVS) has several properties that make it amenable to development as a gene delivery vector. HVS offers the potential to incorporate large amounts of heterologous DNA and infect a broad range of human cell lines. Upon infection the viral genome can persist by virtue of episomal maintenance and stably maintains heterologous gene expression. Here we report an evaluation of the in vivo properties of HVS, with a view to its development as a gene delivery system. We demonstrate for the first time, the long-term persistence of the HVS genome in tumour xenografts generated from HVS-infected human carcinoma cell lines. The HVS-based vector remained latent in the xenograft without spreading to other organs. Moreover, the long-term in vivo maintenance of the HVS genome, as a nonintegrated circular episome, provided efficient sustained expression of a heterologous transgene. These in vivo results suggest that HVS-based vectors have potential for gene therapy applications.

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Acknowledgements

We wish to thank Helmut Fickenscher (University of Erlangen, Germany) for the HVS-transformed B133 cell line; Olusola Faluyi and Konstantina Grosios (Molecular Medicine Unit, Leeds, UK) for assistance with sectioning and immunohistochemistry analysis, respectively. This work was supported in parts by grants to AW from Medical Research Council, Candlelighter's Trust, Yorkshire Cancer Research and Association of International Cancer Research.

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  1. Molecular Medicine Unit, University of Leeds, St James's University Hospital, Leeds, LS9 7TF, UK

    PG Smith, PL Coletta, AF Markham & A Whitehouse

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  1. PG Smith
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Smith, P., Coletta, P., Markham, A. et al. In vivo episomal maintenance of a herpesvirus saimiri-based gene delivery vector. Gene Ther 8, 1762–1769 (2001). https://doi.org/10.1038/sj.gt.3301595

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