Search and rescue: Engineering targeted cell delivery for repair of the central nervous system

Over the last decade, advances in genome engineering and stem cell biology have massively expanded the potential of engineered cells as therapeutics. However, engineering mammalian cells remains limited by inefficient methods of genome engineering, slow workflows, and unpredictable outcomes. As a chemical engineer working at the intersection of stem cell biology, synthetic biology, and molecular systems biology, I aim to make the programming of human cells fast, reliable, and efficient. Using a combination of molecular engineering and computational modeling, my lab is accelerating the rate at which we develop genetic programs to scalably engineer cells for diverse applications in biotechnology and biomedical research including neuron replacement therapies. Engineering cells to deliver themselves to sites of damage solves one important hurdle in scaling neuron replacement therapies to the growing number of patients suffering from CNS trauma and neurodegeneration.

Dr. Katie Galloway's research focuses on defining the fundamental principles of how to integrate synthetic circuitry into native gene regulatory processes and networks to drive cellular behaviors. While a graduate student at Caltech, Dr. Galloway designed, constructed, and tuned wrap-around RNA-based genetic control systems capable of dynamically programming cell fate in yeast. Developing tools that reliably guide cells from one identity to another provides an essential foundation for realizing the promise of synthetic biology in translational therapies. However, building tools that predictably control cell processes and fate remains a challenge in primary cells and stem cells. As a postdoc training in stem cell biology and neuroscience, she worked to improve the process of conversion of mouse and human skin cells into motor neurons. At MIT, her lab uses these insights to streamline the reprogramming process and deliver reprogrammed neurons in vivo. Harnessing insights from biophysics, synthetic biology, molecular biology, and gene regulation, the Galloway Lab is now building genetic control systems. With these control systems, they can tailor the delivery of therapeutic molecules and drive changes in cell fate. With these tools and insights, Dr. Galloway is improving the performance of engineered cells and enhancing cellular reprogramming approaches for regenerative medicine.

My lab aims to change how we deliver neuron replacement therapies by engineering cells to deliver themselves. Instead of relying on invasive direct injections, we will use synthetic biology to program induced pluripotent stem cells into a smart therapeutic called "Search and Rescue". These cells will be programmed to deliver themselves to sites of damage and then repair damaged tissue. In the first phase of Search and Rescue, engineered microglia-like cells will home to sites of injury. Once at these sites, we will direct these cells to convert into neurons that can regenerate damaged neural tissue. Search and Rescue combines synthetic biology, gene circuits, stem cells, and transcription factor-mediated forward programming to improve cell therapy delivery. By solving the challenge of cell delivery, this technology will support efficient and effective repair of the brain and nervous systems from neurodegenerative diseases, strokes, and injuries.

"Production and delivery of neural cells remains a significant barrier to providing effective cell-based therapies for repair of the central nervous system. The MIND Prize allows us to take this next, bold step to synthesizing advances in synthetic biology and stem cell biology which will transform how we deliver cell therapies to repair the central nervous system."