Innovations in Yeast Synthetic Biology: Engineered Discovery Systems for Immunotherapy

Yeast-based platforms are emerging as innovative synthetic biology tools for the discovery of immunotherapeutic proteins. Through the integration of (i) high-throughput surface display technologies, (ii) automated evolution systems (such as OrthoRep), and (iii) computational design strategies, the field of synthetic biology can make a direct impact toward rapidly identifying and engineering novel protein-based therapeutics. In this review, we will highlight the latest innovations regarding using engineered yeast to display proteins (e.g., nanobodies) and screen for potential antigens for immune receptors (e.g., GPCRs, TCRs). We will also discuss emerging areas in which the field has recently progressed and how the innovative technologies from these efforts help bridge the gap between synthetic biology and immunology such as identifying therapeutic binding events for engineered proteins of interest with the potential to actuate downstream immune responses. These innovations illustrate how yeast enables new design, build, test, and learn (DBTL) workflows in immunoengineering and offers a scalable, programmable chassis for developing tools and technologies for the construction of next-generation biotherapeutics.