Genome-Wide CRISPR Screen Identifies GJB2 and BET1L as Barriers to Editing Efficiency

A six-year project led by Professor Krishanu Saha at the University of Wisconsin–Madison screened more than 19,000 human genes to find cellular factors that impede nonviral CRISPR genome editing, published in Nature Communications. The team narrowed 19,144 candidate genes to 26 whose disruption improved editing efficiency, then validated two — GJB2 and BET1L — whose knockout boosted base-editor efficiency more than sixfold in human model cell systems. In patient-derived retinal cells carrying mutations for Leber congenital amaurosis, inhibiting the two genes more than tripled gene-editing efficiency, suggesting transient co-suppression of these genes as a strategy to improve delivery and efficacy of future CRISPR gene therapies.