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Oncolytic Herpes Simplex Virus Engineering and Preparation

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Oncolytic Viruses

Part of the book series: Methods in Molecular Biology ((MIMB,volume 797))

Abstract

Herpes simplex virus-1 (HSV-1) is an enveloped, double-stranded DNA virus that has been used with modification as an oncolytic virus against a number of tumor types. Modifications that make HSV-1 replication-­conditional, i.e., selectively divide in replicating cells make it fulfill a prerequisite criteria for oncolytic viruses. Other appealing features of HSV-1 as an oncolytic virus include its large, modifiable genome; its sensitivity to antiviral agents, such as ganciclovir; and its lack of host cell integration. Here, we review the methods of HSV-1 engineering, through traditional recombination techniques as well as through bacterial artificial chromosome (BAC) technology. We then describe protocols for titering, amplification, and purification of engineered HSV-1-derived oncolytic viruses.

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References

  1. Chiocca, E. A. (2002). Oncolytic viruses. Nat Rev Cancer2, 938–50.

    Article  Google Scholar 

  2. Aghi, M., and Chiocca, E. A. (2003). Genetically engineered herpes simplex viral vectors in the treatment of brain tumors: a review. Cancer Invest21, 278–92.

    Article  CAS  Google Scholar 

  3. Shen, Y., and Nemunaitis, J. (2006). Herpes simplex virus 1 (HSV-1) for cancer treatment. Cancer Gene Ther13, 975–92.

    Article  CAS  Google Scholar 

  4. Aghi, M., and Martuza, R. (2005). Oncolytic viral therapies - the clinical experience. Oncogene24, 7802–16.

    Article  CAS  Google Scholar 

  5. Martuza, R. L., Malick, A., Markert, J. M., Ruffner, K. L., and Coen, D. M. (1991). Experimental therapy of human glioma by means of a genetically engineered virus mutant. Science252, 854–6.

    Article  CAS  Google Scholar 

  6. Markert, J. M., Parker, J. N., Buchsbaum, D. J., Grizzle, W. E., Gillespie, G. Y., and Whitley, R. J. (2006). Oncolytic HSV-1 for the treatment of brain tumours. Herpes : the journal of the IHMF13, 66–71.

    Google Scholar 

  7. Mineta, T., Rabkin, S. D., Yazaki, T., Hunter, W. D., and Martuza, R. L. (1995). Attenuated multi-mutated herpes simplex virus-1 for the treatment of malignant gliomas. Nat Med1, 938–43.

    Article  CAS  Google Scholar 

  8. Kramm, C. M., Chase, M., Herrlinger, U., Jacobs, A., Pechan, P. A., Rainov, N. G., Sena-Esteves, M., Aghi, M., Barnett, F. H., Chiocca, E. A., and Breakefield, X. O. (1997). Therapeutic efficiency and safety of a second-generation replication-conditional HSV1 vector for brain tumor gene therapy. Hum Gene Ther8, 2057–68.

    Article  CAS  Google Scholar 

  9. Ino, Y., Saeki, Y., Fukuhara, H., and Todo, T. (2006). Triple combination of oncolytic herpes simplex virus-1 vectors armed with interleukin-12, interleukin-18, or soluble B7-1 results in enhanced antitumor efficacy. Clin Cancer Res12, 643–52.

    Article  CAS  Google Scholar 

  10. Fukuhara, H., Ino, Y., Kuroda, T., Martuza, R., and Todo, T. (2005). Triple gene-deleted oncolytic herpes simplex virus vector double-armed with interleukin 18 and soluble B7-1 constructed by bacterial artificial chromosome-mediated system. Cancer Research65, 10663–8.

    Article  CAS  Google Scholar 

  11. Todo, T., Martuza, R. L., Rabkin, S. D., and Johnson, P. A. (2001). Oncolytic herpes simplex virus vector with enhanced MHC class I presentation and tumor cell killing. Proc Natl Acad Sci USA98, 6396–401.

    Article  CAS  Google Scholar 

  12. Chou, J., Kern, E. R., Whitley, R. J., and Roizman, B. (1990). Mapping of herpes simplex virus-1 neurovirulence to gamma 134.5, a gene nonessential for growth in culture. Science250, 1262–6.

    Article  CAS  Google Scholar 

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Acknowledgments

The authors wish to thank Drs. Samuel Rabkin, Riyuchi Kanai, and Slawomir Antoszczyk for the figures and assistance. PKA is supported by a continuing clinical research grant from the Doris Duke Charitable Foundation. MKA was supported by a research grant from the American Brain Tumor Association (ABTA) at the time studies cited in this chapter were completed.

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Correspondence to Manish K. Aghi .

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Agarwalla, P.K., Aghi, M.K. (2012). Oncolytic Herpes Simplex Virus Engineering and Preparation. In: Kirn, D., Liu, TC., Thorne, S. (eds) Oncolytic Viruses. Methods in Molecular Biology, vol 797. Humana, Totowa, NJ. https://doi.org/10.1007/978-1-61779-340-0_1

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  • DOI: https://doi.org/10.1007/978-1-61779-340-0_1

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  • Publisher Name: Humana, Totowa, NJ

  • Print ISBN: 978-1-61779-339-4

  • Online ISBN: 978-1-61779-340-0

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