Engineering Synthetic Gene Circuits for Bacterial Therapeutic Delivery In Vivo

Engineering bacteria to locally sense and produce therapeutics in disease sites such as tumors is emerging as a promising application of synthetic biology. However, a central challenge for translating this next-generation therapy to clinics is the precise control of bacterial behavior in vivo. We recently constructed a library of biosensors and therapeutic payloads, and rapidly characterized their performance in a novel 3D multicellular co-culture platform that recapitulates bacterial tumor colonization. Using this system, bacteria were engineered to selectively grow in tumor-specific environmental conditions and deliver payloads. In murine cancer models, we demonstrated that the engineered bacteria improved safety and efficacy profiles. These approaches can be utilized towards accelerating the development of therapeutic bacteria for clinical applications.