Genetically-encoded degraders as versatile modulators of intracellular therapeutic targets

Abstract

Targeted protein degradation (TPD) is an emerging therapeutic approach that has attracted significant interest. The traditional TPD degraders rely on small molecules that can only target proteins of interest (POI) with known small-molecule binders or appropriate binding pockets. Recently, several genetic-encoded TPD (GE-TPD) strategies have been developed in which the degrader molecules are expressed in cells based on genetic information. GE-TPD discovers POI binders through techniques such as yeast and phage display and expands the E3 ligase toolbox through genetic encoding. In this review, we assess the progress of GE-TPD technologies in recent years and highlight innovative technologies that have the potential to advance the development of GE-TPD.