Cell-Free Synthetic Biology:Serving Society with Supernatural Processes and Products

Biology is amazing! Organisms and biological processes are incredibly versatile and yet, as our understanding grows, logical in their design and function. Nonetheless, the complexity of biological systems can be daunting. Cells have evolved to conquer multiple challenges and, most importantly, to be resilient self-replicating factories. But we don't need all this to provide important services and products. Cell-free synthetic biology now lets us activate and combine individual biological subsystems to focus on a single objective. This talk will begin by describing how this ability emerged through a series of foundational advances.

As modern cell-free technology emerged, we gained the ability to directly modify, monitor, and control intracellular processes. For example, in a single uniformly mixed reactor we activated synergistic processes that normally occurred in different subcellular compartments. This suggested the potential for supernatural capabilities. We next activated cell membrane dependent processes to economically supply biochemical energy. When non-natural amino acids with biologically orthogonal reactivities were efficiently introduced, we then gained the ability to make supernatural multi-functional molecules and molecular assemblies.

Now Sutro Biopharma has applied and scaled up this foundational technology to make innovative pharmaceuticals such as precisely designed antibody drug conjugates. These are now showing promise in human clinical trials. Innovative biosensor technology has also been produced, and complex adaptive control networks have been activated. More recently, feasibility for small on-demand biopharmaceutical production facilities has been demonstrated. This exciting development offers a new approach to pharmaceutical production and also motivates new concepts for protein pharmaceutical QA and QC. It may also facilitate globalization of cell-free biotechnologies. These are exciting times, and the talk will conclude with glimpses of new cell-free technology platforms that could enable rapid, effective vaccine responses as well as smart nanoparticles that finally provide the magic bullets for precisely targeting diseased tissues such as tumors.