Summary
Virus vectors have been employed as gene transfer vehicles for various pre-clinical and clinical gene therapy applications. Replication-competent herpes simplex virus (HSV) vectors that replicate specifically in actively dividing glial tumor cells have been used in Phase I–II human trials in patients with glioblastoma multiforme (GBM), a fatal form of brain cancer. Research during the last decade on the development of HSV vectors has resulted in the engineering of recombinant vectors that are totally replication defective, non-toxic, and capable of long-term transgene expression. This chapter describes methods for the construction of recombinant genomic HSV vectors based on the HSV-1 replication-defective vector backbones, steps in their purification, and their small-scale production for use in cell culture experiments as well as studies in animals.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Roizman, B. and Knipe, D.M. (2001) Herpes simplex viruses and their replication, in Fields Virology, 4th edition (Knipe, D.M. and Howley, P.M., eds.), Lippincott Williams and Wilkins, Philadelphia, PA, pp. 2399–2459.
Mackem, S. and Roizman, B. (1982) Structural features of the herpes simplex virus alpha gene 4, 0, and 27 promoter-regulatory sequences which confer alpha regulation on chimeric thymidine kinase. J. Virol. 44, 939–949.
Oroskar, A. and Read, G. (1989) Control of mRNA stability by the virion host shutoff function of herpes simplex virus. J. Virol. 63, 1897–1906.
Burton, E.A., Wechuck, J.B., Wendell, S.K., Goins, W.F., Fink, D.J., and Glorioso, J.C. (2001) Multiple applications for replication-defective herpes simplex virus vectors. Stem Cells 19, 358–377.
Goins, W.F., Wolfe, D., Krisky, D.M., Bai, Q., Burton, E.A., Fink, D.J., and Glorioso, J.C. (2004) Delivery using herpes simplex virus: an overview. Methods Mol. Biol. 246, 257–299.
Wolfe, D., Goins, W.F., Yamada, M., Moriuchi, S., Krisky, D.M., Oligino, T.J., Marconi, P.C., Fink, D.J., and Glorioso, J.C. (1999) Engineering herpes simplex virus vectors for CNS applications. Exp. Neurol. 159, 34–46.
Glorioso, J., Goins, W., Meaney, C., Fink, D., and DeLuca, N. (1994) Gene transfer to brain using herpes simplex virus vectors. Ann. Neurol. 35, S28–34.
Haarr, L., Shukla, D., Rodahl, E., Dal Canto, M., and Spear, P. (2001) Transcription from the gene encoding the herpesvirus entry receptor nectin-1 (HveC) in nervous tissue of adult mouse. Virology 287, 301–309.
Mata, M., Zhang, M., Hu, X., and Fink, D. (2001) HveC (nectin-1) is expressed at high levels in sensory neurons, but not in motor neurons of the rat peripheral nervous system. J. NeuroVirol. 7, 1–5.
Goins, W.F., Lee, K.A., Cavalcoli, J.D., O’Malley, M.E., DeKosky, S.T., Fink, D.J. and Glorioso, J.C. (1999) Herpes simplex virus type 1 vector-mediated expression of nerve growth factor protects dorsal root ganglia neurons from peroxide toxicity. J. Virol. 73, 519–532.
Goins, W.F., Sternberg, L.R., Croen, K.D., Krause, P.R., Hendricks, R.L., Fink, D.J., Straus, S.E., Levine, M. and Glorioso, J.C. (1994) A novel latency-active promoter is contained within the herpes simplex virus type 1 \(U_{L}\) flanking repeats. J. Virol. 68, 2239–2252.
Goins, W.F., Yoshimura, N., Ozawa, h., Yokoyama, T., Phelan, M., Bennet, N., deGroat, W.C., Glorioso, J.C. and Chancellor, M.B. (2000) Herpes simplex virus vector-mediated nerve growth factor expression in bladder and afferent neurons: potential treatment for diabetic bladder dysfunction. J. Urol. 165, 1748–1754.
Akkaraju, G.R., Huard, J., Hoffman, E.P., Goins, W.F., Pruchnic, R., Watkins, S.C., Cohen, J.B. and Glorioso, J.C. (1999) Herpes simplex virus vector-mediated dystrophin gene transfer and expression in MDX mouse skeletal muscle. J. Gene Med. 1, 280–289.
Krisky, D.M., Marconi, P.C., Oligino, T.J., Rouse, R.J., Fink, D.J., Cohen, J.B., Watkins, S.C., and Glorioso, J.C. (1998a) Development of herpes simplex virus replication-defective multigene vectors for combination gene therapy applications. Gene Ther. 5, 1517–1530.
Honess, R. and Roizman, B. (1974) Regulation of herpes simplex virus macromolecular synthesis. I. Cascade regulation of the synthesis of three groups of viral proteins. J. Virol. 14, 8–19.
DeLuca, N.A., McCarthy, A.M., and Schaffer, P.A. (1985) Isolation and characterization of deletion mutants of herpes simplex virus type 1 in the gene encoding immediate-early regulatory protein ICP4. J. Virol. 56, 558–570.
Johnson, P., Miyanohara, A., Levine, F., Cahill, T., and Friedmann, T. (1992) Cytotoxicity of a replication-defective mutant herpes simplex virus type 1. J. Virol. 66, 2952–2965.
Krisky, D.M., Wolfe, D., Goins, W.F., Marconi, P.C., Ramakrishnan, R., Mata, M., Rouse, R.J., Fink, D.J., and Glorioso, J.C. (1998b) Deletion of multiple immediate-early genes from herpes simplex virus reduces cytotoxicity and permits long-term gene expression in neurons. Gene Ther. 5, 1593–1603.
Samaniego, L., Webb, A., and DeLuca, N. (1995) Functional interaction between herpes simplex virus immediate-early proteins during infection: gene expression as a consequence of ICP27 and different domains of ICP4. J. Virol. 69, 5705–5715.
Wu, N., Watkins, S.C., Schaffer, P.A., and DeLuca, N.A. (1996) Prolonged gene expression and cell survival after infection by a herpes simplex virus mutant defective in the immediate-early genes encoding ICP4, ICP27, and ICP22. J. Virol. 70, 6358–6368.
Krisky, D., Marconi, P., Oligino, T., Rouse, R., Fink, D., and Glorioso, J. (1997) Rapid method for construction of recombinant HSV gene transfer vectors. Gene Ther. 4, 1120–1125.
Marconi, P., Krisky, D., Oligino, T., Poliani, P.L., Ramakrishnan, R., Goins, W.F., Fink, D. J., and Glorioso, J.C. (1996) Replication-defective HSV vectors for gene transfer in vivo. PNAS 93, 11319–11320.
Markert, J., Medlock, M., Rabkin, S., Gillespie, G., Todo,T., Hunter, W., Palmer, C., Feigenbaum, F., Tornatore, C., Tufaro, F., and Martuza, R. (2000). Conditionally replicating herpes simplex virus mutant, G207 for the treatment of malignant glioma: results of a phase I trial. Gene Ther. 7, 867–874.
Rampling, R., Cruickshank, G., Papanastassiou, V., Nicoll, J., Hadley, D., Brennan, D., Petty, R., MacLean, A., Harland, J., McKie, E., Mabbs, R., and Brown, M. (2000) Toxicity evaluation of replication-competent herpes simplex virus (ICP 34.5 null mutant 1716) in patients with recurrent malignant glioma. Gene Ther. 7, 859–866.
Author information
Authors and Affiliations
Rights and permissions
Copyright information
© 2008 Humana Press, a part of Springer Science+Business Media, LLC
About this protocol
Cite this protocol
Goins, W.F., Krisky, D.M., Wechuck, J.B., Huang, S., Glorioso, J.C. (2008). Construction and Production of Recombinant Herpes Simplex Virus Vectors. In: Gene Therapy Protocols. Methods in Molecular Biology™, vol 433. Humana Press. https://doi.org/10.1007/978-1-59745-237-3_6
Download citation
DOI: https://doi.org/10.1007/978-1-59745-237-3_6
Publisher Name: Humana Press
Print ISBN: 978-1-58829-903-1
Online ISBN: 978-1-59745-237-3
eBook Packages: Springer Protocols