1. ¹Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa Health Research Institute, Centre for Cancer Therapeutics, Ottawa, Ontario, Canada
2. ²Department of Pathology and Molecular Medicine, Centre for Gene Therapeutics, Michael DeGroote Centre for Learning and Discovery McMaster University, Ottawa, Ontario, Canada

Correspondence: John C. Bell, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa Health Research Institute, Centre for Cancer Therapeutics, 503 Smyth Road, Ottawa, Ontario K1H 8L6, Canada. E-mail: jbell@ohri.ca

Received 20 March 2008; Accepted 15 May 2008; Published online 17 June 2008.

Abstract

Creation of potent oncolytic viruses (OVs) suitable for the clinic may require new strategies in virus design. Replication-competent viruses facilitate a variety of approaches to achieving tumor specificity. Altered expression of microRNAs is a common hallmark of cancer that we demonstrate can be used to alter expression of a potent wild-type viral gene to achieve tumor-specific replication of an engineered vesicular stomatitis virus (VSV). Incorporation of let-7 microRNA complementary sequences within VSV eliminates undesirable replication and associated toxicity in normal cells but permits growth in cancer cells in vitro and in vivo. This is proof of concept that viruses designed to exploit the differential microRNA expression in cancer cells is a viable approach, potentially useful in optimizing oncolytic viral gene expression for maximal antitumor activity and safety.