CRISPR/Cas9 gene editing has made possible a multitude of biomedical experiments including studies that systematically turn off genes in cancer cells to look for ones that the cancer cells heavily depend on to survive and grow. These genes, or “cancer dependencies,” are often promising drug targets. But new research shows that many of these CRISPR screening experiments rely on components, called CRISPR/Cas9 guides, that do not perform equally well in cells from people of all ancestries, which can cause CRISPR screens to miss cancer dependencies.
These CRISPR guides are short sequences of RNA that steer the CRISPR Cas9 enzyme to a specific site in the genome to cut DNA and deactivate a targeted gene. The new findings, from scientists at the Broad Institute of MIT and Harvard, show about 2 percent of these guides miss their target. This means that Cas9 won’t make a cut and disable a specific gene, thereby obscuring a potential role of that gene in cancer growth. The team found that this happens disproportionately in cells from people of African ancestry, because CRISPR guides were designed using reference genomes from people who are largely of European ancestry and do not fully represent global genetic diversity.
