(316g) Enabling Design-Driven Medicine with Synthetic Biology: Engineering Programmable Cell-Based Therapies

The complementary disciplines of systems biology and synthetic biology are enabling a transformation in the development and implementation of effective treatments for a broad range of patients and diseases. These technologies allow us to consider health and disease at a systems level, and increasingly, to translate this understanding into the design of novel therapies that overcome existing clinical barriers. Here, I will describe our efforts to harness this new paradigm to enable cancer immunotherapy. In part, we are building understanding of the local immune dysfunction that currently limits therapeutic efficacy, and our systems-level investigations have revealed novel insights into how these multicellular networks develop and persist. In order to translate these insights into therapies, we are also developing technologies that enable us to engineer programmable mammalian cell-based therapies. The emerging field of synthetic biology provides an approach for building novel cellular functions from the bottom up, and the “toolbox” of biological parts that operate in mammalian cells is rapidly expanding. To date, however, we lack the ability to construct synthetic cell-based biosensors that detect and respond to many physiologically relevant environmental cues. Here, I will discuss our work developing novel synthetic biology tools that address this need, enabling the constructs of living devices that interface robustly with host physiology. I will also discuss our application of these technologies to probe and modulate interactions between cancer and the immune system, illustrating the potential of this emerging paradigm of design-driven medicine.