Imaging immediate-early and strict-late promoter activity during oncolytic herpes simplex virus type 1 infection and

S Yamamoto1, L A Deckter, K Kasai

  • 1Dardinger Laboratory for Neuro-oncology and Neurosciences, Department of Neurological Surgery, James Cancer Hospital and Solove Research Institute, The Ohio State University Medical Center, Columbus, OH, USA.

Gene Therapy
|July 28, 2006
PubMed

Insights

This study developed oncolytic herpes simplex virus type 1 (HSV-1) for cancer therapy. Luciferase imaging effectively monitored viral infection and replication in tumors, aiding preclinical studies.

Area of Science:

  • Oncolytic virotherapy
  • Molecular imaging
  • Cancer research

Background:

  • Oncolytic viruses are promising cancer therapeutics.
  • Non-invasive monitoring of oncolytic virotherapy is crucial.
  • Luciferase imaging offers a sensitive method for tracking viral activity.

Purpose of the Study:

  • To develop and evaluate oncolytic herpes simplex virus type 1 (HSV-1) vectors for cancer therapy.
  • To utilize luciferase reporter systems for monitoring viral infection and replication in real-time.
  • To assess the utility of strict-late promoter-driven luciferase expression for evaluating tumor oncolysis.

Main Methods:

  • Generated replication-conditional HSV-1 mutants deleted for U(L)39 and gamma(1)34.5.
  • Engineered HSV-1 vectors to express firefly luciferase under immediate-early (IE4/5) or strict-late (gC) promoters.
  • Evaluated luciferase expression in cultured cells and a mouse tumor model.

Main Results:

  • Luciferase expression driven by IE and strict-late promoters confirmed viral infection and replication, respectively.
  • IE promoter-driven luciferase indicated initial viral entry and gene expression.
  • Strict-late promoter-driven luciferase accurately reflected viral replication dynamics.

Conclusions:

  • Luciferase-based bioluminescence is a viable tool for monitoring oncolytic HSV-1 infection and replication.
  • Strict-late promoter-driven luciferase expression is particularly useful for assessing tumor oncolysis in preclinical settings.
  • These engineered HSV-1 vectors hold potential for advancing cancer virotherapy research.