Redesigning human cells as living medicines

One of the central motivations of our lab is to engineer curative treatments that replace a lifetime of pills and injections with a single one-off implant of living drugs that will continuously monitor and treat disease.

Active therapeutic devices that interact directly with the fundamental cellular and molecular causes of disease will be transformative for medicine. The huge success of peptide and protein-based drugs offers the opportunity for these agents to be generated in situ at the disease site. Our goal is to extend this to synthesizing and secreting therapeutic agents in response to external stimuli --such as molecules that are related to specific diseases. The most tractable approach is to use existing biological cells as the basis for such devices.

Living cells are advantageous as they maintain a homeostatic environment distinct from their surroundings and integrate a wide variety of input signals to execute context-dependent actions. These highly sophisticated computers are contained in a package that is a fraction of a cubic millimeter, has its own power supply, repair mechanisms, and works when wet. Each of the distinct cell types in the human body therefore represents a potential basic chassis for the design of a cellular therapeutic device.

We design proteins and the supporting genetic circuitry, and transfer it directly to cell genomes. Alternatively we build an additional micro-chromosome containing the genetic circuitry, and then transfer it to the host cell.

Our goal is curative or quasi-curative treatments that provide localized treatment, ensure guaranteed compliance, and deliver a highly nuanced response to fluctuating disease severity.