Engineered bacteria launch and control an oncolytic virus

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 wherebyS. typhimuriumbacteria transcribe and deliver the Senecavirus A RNA genome inside host cells, launching a potent oncolytic viral infection. Then, we engineer the virus to require a bacterially delivered protease in order to achieve virion maturation, demonstrating bacterial control over the virus. This work extends bacterially delivered therapeutics to viral genomes, and the governing of a viral population through engineered microbial interactions.One-Sentence SummaryBacteria are engineered to act as a synthetic “capsid” delivering Senecavirus A genome and controlling its spread.