Evolution of oncolytic viruses

•Directed evolution has only seldom applied to oncolytic virotherapy.•Basic experimental evolution studies provide a basis for oncolytic virus evolution.•Evolutionary considerations are relevant to oncolytic virus safety.

Owing to their replicative capacity, oncolytic viruses (OVs) can evolve under the action of natural selection. Reversion to virulence and recombination with wild-type strains may compromise OV safety, therefore requiring evolutionary risk assessment studies. On the other hand, evolution can be directed in the laboratory to create more potent and safer OVs. Previous work in the experimental evolution field provides a background for OV directed evolution, and has identified interesting exploitable features. While genetic engineering has greatly advanced the field of oncolytic virotherapy, this approach is sometimes curtailed by the complexity and diversity of virus–host interactions. Directed evolution provides an alternative approach that may help to obtain new OVs without prejudice toward the underlying molecular mechanisms involved.