PINCER: improved CRISPR/Cas9 screening by efficient cleavage at conserved residues.

ABSTRACT: CRISPR/Cas9 functional genomic screens have emerged as essential tools in drug target discovery. However, the sensitivity of available genome-wide CRISPR libraries is impaired by guides which inefficiently abrogate gene function. While Cas9 cleavage efficiency optimization and essential domain targeting have been developed as independent guide design rationales, no library has yet combined these into a single cohesive strategy to knock out gene function. Here, in a massive reanalysis of CRISPR tiling data using the most comprehensive feature database assembled, we determine which features of guides and their targets best predict activity and how to best combine them into a single guide design algorithm. We present the ProteIN ConsERvation (PINCER) genome-wide CRISPR library, which for the

SUBMITTER: Veeneman B 

PROVIDER: S-EPMC7515706 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature