Abstract

AbstractThe ability of bacteria and viruses to selectively replicate in tumors has led to synthetic engineering of new microbial therapies. Here we design a cooperative strategy whereby S. typhimurium bacteria transcribe and deliver the Senecavirus A RNA genome inside host cells, launching a potent oncolytic viral infection. "Encapsidated" by bacteria, the viral genome can further bypass circulating antiviral antibodies to reach the tumor and initiate replication and spread within immune mice. Finally, we engineer the virus to require a bacterially delivered protease to achieve virion maturation, demonstrating bacterial control over the virus. This work extends bacterially delivered therapeutics to viral genomes, and shows how a consortium of microbes can achieve a cooperative aim.