Awakening the Genome: CRISPR Activation to Unravel the Origin and Vulnerabilities of Cancer

CRISPR activation (CRISPRa) co-opts nuclease-dead Cas-molecule DNA-binding capabilities to direct transcriptional activators to specific loci, driving gene expression. CRISPRa technology has advanced rapidly in the past few years, and it is now applicable to a wide range of biological questions, including the study of cancer. In this review, we discuss the different forms of CRISPRa technologies, their in vitro and in vivo applications, and recent studies that have used CRISPRa in their cancers of choice. We further discuss the different CRISPRa tools that are available, including mouse models and single-guide RNA libraries. Finally, we examine the maturation of CRISPRa, as its potential therapeutic applications are beginning to be explored.