Researchers from the Broad Institute and Dana-Farber Cancer Institute identified that CRISPR-Cas9 guide RNA efficiency varies by ancestry, with off-target effects occurring more frequently in cell lines of African ancestry compared to others. This disparity, published in Nature Communications, indicates that current CRISPR screening methodologies may systematically miss essential cancer dependencies in diverse populations, potentially overlooking key therapeutic targets. The findings underscore the need for guide RNA designs that account for genetic diversity to improve cancer research and drug discovery.