The Reoviridae are a family of viruses with a non-enveloped icosahedral capsid and a segmented double-stranded RNA genome. Prototypes of the mammalian Orthoreoviruses have been isolated from human respiratory and enteric tracts and are not associated with human disease. One of these, human reovirus type 3 Dearing (T3D), usually serves as a model for the family. In the last decade the mammalian Orthoreoviruses, especially T3D, have been evaluated as oncolytic agents in experimental cancer therapy. This is based on the observation that reoviruses induce cell death in tumor cells, but not in healthy non-transformed cells. Cancer cells have developed all kinds of strategies to escape control of normal regulators in tissue. If the strategy involves evading cell death pathways on which the reovirus relies on for replication or if the expression of the canonical receptor is diminished, the effect of the therapy is severely reduced. To boost the oncolytic potency of reoviruses in tumor cells that resist reovirus infection and replication, we used two strategies; 1) a bioselection procedure to select for reoviurses that can replicate in cells lacking the receptor and 2) genetic modification to insert small transgenes in one of the reovirus dsRNA segments (S1).UBL - phd migration 201
