Combinatorial screening of biological degrader modules to destroy intractable proteins – Kinetic Data

Abstract – kinetic data Targeted protein degradation is a potent strategy against intracellular proteins impervious to traditional drugs. We describe a platform reliant on high-throughput cloning and mRNA-based delivery to quickly screen 100s-1000s modular biological degraders which we challenge against the intractable and high-turnover c-Myc oncoprotein. We uncover critical principles to drive the discovery of degraders against any target, capable of operating without prior cell line engineering, with direct applications in research and potentially therapy.