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Generation of adenoviruses encoding the herpes simplex virus vhs gene: A novel strategy to generate adenoviruses expressing genes toxic to producer cells

Cancer Gene Therapy volume 8, pages 566–572 (2001)Cite this article

Abstract

Adenovirus vectors expressing suicide genes represent a promising approach for cancer gene therapy. We wanted to determine whether the virion host shutoff ( vhs ) gene of herpes simplex virus could be used as a suicide gene for gene therapy of glioblastomas. The vhs gene was cloned downstream of the glial fibrillary acidic protein promoter to direct tissue-specific expression, and recombinant adenoviruses were generated in 293 cells. Viruses, which contained the vhs gene but did not express it, could readily be isolated; however, we were unable to plaque purify viruses that expressed vhs protein. We constructed a derivative of 293 cells expressing an antisense RNA to the vhs gene and used them to generate adenovirus vectors that express vhs protein. These cells were used to complement vhs -expressing adenoviruses through three rounds of plaque purification. This approach could be generalized to produce adenovirus vectors expressing other toxic transgenes. Cancer Gene Therapy (2001) 8, 566–572

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Acknowledgements

We thank G.S. Read for kindly providing the anti- vhs antisera and J. Koga for helpful discussions. We also thank Kathleen Hiemstra Brite for excellent technical assistance and Debra Parker for her help in preparation of this manuscript.

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  1. JCR Biopharmaceuticals, San Diego, 92121, California, USA

    Gary M Glenn & Subhendra Chatterjee

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  1. Gary M Glenn
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  2. Subhendra Chatterjee
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Correspondence to Subhendra Chatterjee.

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Glenn, G., Chatterjee, S. Generation of adenoviruses encoding the herpes simplex virus vhs gene: A novel strategy to generate adenoviruses expressing genes toxic to producer cells. Cancer Gene Ther 8, 566–572 (2001). https://doi.org/10.1038/sj.cgt.7700339

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