A new era in functional genomics screens

The past 25 years of genomics research first revealed which genes are encoded by the human genome and then a detailed catalogue of human genome variation associated with many diseases. Despite this, the function of many genes and gene regulatory elements remains poorly characterized, which limits our ability to apply these insights to human disease. The advent of new CRISPR functional genomics tools allows for scalable and multiplexable characterization of genes and gene regulatory elements encoded by the human genome. These approaches promise to reveal mechanisms of gene function and regulation, and to enable exploration of how genes work together to modulate complex phenotypes. In this Review, Przybyla and Gilbert describe the latest approaches for CRISPR-based functional genomics screens, including the adoption of single-cell transcriptomic read-outs and applications in characterizing the non-coding genome and mapping genetic interactions at scale.