Director R&D Broad Institute, Massachusetts, United States
CRISPR technology has enabled the manipulation of genetic information with tremendous scale and flexibility. Here we will present screens utilizing Base Editor technology, which enables amino-acid-level resolution of drug-target interactions. Such screens can be used to identify a resistance mutation that helps to prove the actual target of a less-characterized small molecule. Additionally, this approach can provide insight into potential resistance mechanisms long before seeing what arises in patients. The low upfront costs of generating a pooled, base editing library, coupled with the small-scale and relative ease of execution, argues for applying this technique early in the drug discovery process.