(593a) Invited Talk: Conditional Protein Degradation for Cellular Reprogramming

BioPROTACs are heterobifunctional proteins designed for targeted protein degradation (TPD). They are useful not only for probing protein functions but also offer a therapeutic avenue for modulating disease-related proteins. To extend the use of TPD beyond just protein attenuation, we introduce a synthetic framework for logic-gated, switchable TPD to achieve temporal control of protein content. This new synthetic approach allows us to expand the possible protein degradation outcomes in mammalian cells using Boolean logic operations depending on the input combinations. The flexibility to temporally modulate the level of multiple native intracellular proteins can potentially lead to applications from therapy to diagnostics and biotechnology.