Designing and building oncolytic viruses

Maroun, Justin; Muñoz-Alía, Miguel; Ammayappan, Arun; Schulze, Autumn; Peng, Kah-Whye; Russell, Stephen

Viruses can be further engineered to exclusively replicate in tumor cells by combining a virus' needs with physiologic peculiarities intrinsic in tumorigenesis. For example, a virally encoded thymidine kinase (TK) is required for HSV and vaccinia virus infection to increase the supply of deoxynucleotide triphosphates required for synthesis of progeny virus genomes [113, 114] . Elimination of the TK future science group www.futuremedicine.com gene from the viral genome restricts viral replication to cancer cells where there is an upregulation of human TK [115, 116] . Another example of a virus that exploits the high replication rate of tumor cells is Toca-511, a replication competent C-type retrovirus encoding the drug activating enzyme cytosine deaminase (CD) [117] . Since the integration of C-type retroviruses is S-phase dependent [118] , this virus is selectively amplified in rapidly proliferating tumor tissue.