Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 362, Issue 2, Pages 419-424Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2007.08.001
Keywords
adenovirus vector; gene therapy; HSVtk/GCV system; systemic administration; telomere reverse transcriptase promoter
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Adenovirus vectors (Adv) are used widely in cancer gene therapy research. However, the clinical application of Adv currently is limited to local, intratumoral administration; systemic administration leads to redundant transgene expression in the liver and subsequent hepatotoxicity. Here we replaced the conventional cytomegalovirus (CMV) promoter of Adv with a tumor-specific telomere reverse transcriptase (TERT) promoter, to restrict expression of the Adv-transduced transgene to tumor tissue alone. We evaluated the therapeutic and side effects after systemic administration of Adv expressing herpes simplex virus thymidine kinase (Ad-HSVtk) in mice bearing Meth-A tumors. Although systemically injected CNIV promoter-driven Ad-HSVtk lacked therapeutic effect, mice injected with 2 x 10 11 viral particles containing TERT promoter-driven Ad-HSVtk showed inhibited tumor growth and prolonged survival with minimal side effects. Our results suggest that Adv in which transgene expression is driven by the TERT promoter are a promising prototype of tumor-targeting vectors for effective and safe cancer gene therapy. (c) 2007 Elsevier Inc. All rights reserved.
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