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Gene Ther. 2006 Dec;13(24):1731-6. Epub 2006 Jul 27.

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

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Dardinger 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.


An increasing number of oncolytic viruses have been developed and studied for cancer therapy. In response to needs for non-invasive monitoring and imaging of oncolytic virotherapy, several different approaches, including a positron emission tomography-based method, a method using secreted marker peptides, and optical imaging-based methods, have been reported. Among these modalities, we utilized the luciferase-based bioluminescent assay/imaging systems to determine the kinetics and dynamics of a productive viral infection. The replication cycle of herpes simplex virus type 1 (HSV-1) is punctuated by a temporal cascade of three classes of viral genes: immediate-early (IE), early (E) and late (L) genes. U(L)39- and gamma(1)34.5-deleted, replication-conditional HSV-1 mutants that express firefly luciferase under the control of the IE4/5 or strict-late gC promoters were generated. These oncolytic viruses were examined in cultured cells and a mouse tumor model. IE promoter- and strict-late promoter-mediated luciferase expression was confirmed to indicate viral infection and replication, respectively. Incorporation of a strict-late promoter-driven luciferase cassette into oncolytic HSV-1 vectors would be useful for assessing tumor oncolysis in preclinical tumor treatment studies.

[Indexed for MEDLINE]

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