Expression of a fusogenic membrane glycoprotein by an oncolytic herpes simplex virus potentiates the viral antitumor effect

Xinping Fu, Lihua Tao, Aiwu Jin, Richard Vile, Malcolm K. Brenner, Xiaoliu Zhang

Research output: Contribution to journalArticle

78 Scopus citations

Abstract

Oncolytic viruses have shown considerable promise in the treatment of solid tumors, but their potency must be improved if their full clinical potential is to be realized. We inserted the gene encoding a truncated form of the gibbon ape leukemia virus envelope fusogenic membrane glycoprotein (GALV.fus) into an oncolytic herpes simplex virus, using an enforced ligation procedure. Subsequent in vitro and in vivo studies showed that expression of GALV.fus in the context of an oncolytic virus significantly enhances the antitumor effect of the virus. Furthermore, by controlling GALV.fus expression through a strict late viral promoter, whose activity depends on the initiation of viral DNA replication, we were able to express this glycoprotein in tumor cells but not in normal nondividing cells. It will be of interest to confirm whether functional expression of a strong fusogenic gene by an oncolytic herpes simplex virus enhances viral antitumor activity without increasing its toxicity.

Original languageEnglish (US)
Pages (from-to)748-754
Number of pages7
JournalMolecular Therapy
Volume7
Issue number6
DOIs
StatePublished - Jun 1 2003

Keywords

  • Fusogenic membrane glycoprotein
  • Herpes simplex virus
  • Late viral promoter
  • Liver cancer
  • Oncolytic

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

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