The Role of Protein Engineering in Biomedical Applications of Mammalian Synthetic Biology

Engineered proteins with enhanced or altered functionality, generated for example by mutation or domain fusion, are at the core of nearly all synthetic biology endeavors in the context of precision medicine, also known as personalized medicine. From designer receptors sensing elevated blood markers to effectors rerouting signaling pathways to synthetic transcription factors and the customized therapeutics they regulate, engineered proteins play a crucial role at every step of novel therapeutic approaches using synthetic biology. Here, recent developments in protein engineering aided by advances in directed evolution, de novo design, and machine learning are discussed. Building on clinical successes already achieved with chimeric antigen receptor (CAR‐) T cells and other cell‐based therapies, these developments are expected to further enhance the capabilities of mammalian synthetic biology in biomedical and other applications. While DNA encodes all of life's information, proteins perform all necessary functions. This makes protein engineering one of the most important endeavors to modify life in turn, as is the aim of synthetic biology. Here, the newest developments and the evergrowing importance of protein engineering in the mammalian context are presented, spanning applications from basic research up to biomedical therapies.