CRISPR/Cas9 and cDNA overexpression screens to identify transmembrane transporters involved in PROTAC sensitivity/resistance

Proteolysis targeting chimeras (PROTACs) are bifunctional molecules that induce selective protein degradation by linking an E3 ubiquitin ligase enzyme to a target protein. Here we used transporter-focused and genome-wide CRISPR/Cas9 as well as a barcoded solute carriere (SLC)-focused cDNA libraray to screen for transporters that are involved in the resistance or sensitivity to BET- and SLC9-targeting PROTACs. Drug resistance screens with CRISPR/Cas9 and cDNA overexpression libraries in HAP1 cells under PROTAC selection.