Directed Evolution of Oncolytic Viruses

Viruses that selectively infect tumours (oncolytic viruses) constitute a promising therapy against cancer. Many efforts have been made to rationally engineer viruses with improved tumour selectivity, potency, and safety. Nevertheless, such efforts have often been thwarted by our limited knowledge of virus-host interactions, which are extremely complex and varied. Directed evolution constitutes a fundamentally different approach, whereby no a priori knowledge of molecular mechanisms is required, and which takes advantage of a key distinctive feature of viruses compared to conventional therapeutics, that is, their ability to replicate, mutate, and respond to selection. The field of experimental evolution has amply shown that viruses can be readily adapted to different types of environments. However, previous attempts at using directed evolution for improving oncolytic viruses have been restricted to highly simplistic cancer models, mainly standard cell cultures. Here, we propose to investigate the evolution of an oncolytic virus (vesicular stomatitis virus) under more realistic and complex settings.