The Anti-CRISPR Story: A Battle for Survival

The last decade has seen the fields of molecular biology and genetics transformed by the development of CRISPR-based gene editing technologies. These technologies were derived from bacterial defense systems that protect against viral invasion. Elegant studies focused on the evolutionary battle between CRISPR-encoding bacteria and the viruses that infect and kill them revealed the next step in this arms race, the anti-CRISPR proteins. Investigation of these proteins has provided important new insight into how CRISPR-Cas systems work and how bacterial genomes evolve. They have also led to the development of important biotechnological tools that can be used for genetic engineering, including off switches for CRISPR-Cas9 genome editing in human cells. Bacteriophage proteins that inactivate the type I-F CRISPR-Cas system, known as anti-CRISPRs, were first described in 2013. Since then, anti-CRISPR proteins that inhibit the type I-E, II-A, and II-C CRISPR-Cas systems have been identified. This perspective reviews the discovery of anti-CRISPR proteins, summarizes the insight we have gained into their structures and mechanisms of activity, and touches on their potential uses in gene editing technologies.