RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA, USA.
Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Department of Biochemistry, University of Toronto, Toronto, ON, Canada.
Curr Opin Microbiol. 2017 Jun;37:120-127. doi: 10.1016/j.mib.2017.06.003. Epub 2017 Jun 29.
Clustered, regularly interspaced, short, palindromic repeats (CRISPR) loci, together with their CRISPR-associated (Cas) proteins, provide bacteria and archaea with adaptive immunity against invasion by bacteriophages, plasmids, and other mobile genetic elements. These host defenses impart selective pressure on phages and mobile elements to evolve countermeasures against CRISPR immunity. As a consequence of this pressure, phages and mobile elements have evolved 'anti-CRISPR' proteins that function as direct inhibitors of diverse CRISPR-Cas effector complexes. Some of these CRISPR-Cas complexes can be deployed as genome engineering platforms, and anti-CRISPRs could therefore be useful in exerting spatial, temporal, or conditional control over genome editing and related applications. Here we describe the discovery of anti-CRISPRs, the range of CRISPR-Cas systems that they inhibit, their mechanisms of action, and their potential utility in biotechnology.
成簇、规律间隔、短回文重复序列(CRISPR)位点及其相关的 CRISPR 关联(Cas)蛋白为细菌和古菌提供了针对噬菌体、质粒和其他移动遗传元件入侵的适应性免疫。这些宿主防御系统对噬菌体和移动元件施加选择性压力,促使它们进化出对抗 CRISPR 免疫的对策。作为这种压力的结果,噬菌体和移动元件进化出了“抗 CRISPR”蛋白,这些蛋白作为多种 CRISPR-Cas 效应复合物的直接抑制剂发挥作用。其中一些 CRISPR-Cas 复合物可用作基因组工程平台,因此抗 CRISPR 蛋白可用于对基因组编辑和相关应用进行空间、时间或条件控制。在这里,我们描述了抗 CRISPR 蛋白的发现、它们抑制的 CRISPR-Cas 系统的范围、它们的作用机制以及它们在生物技术中的潜在应用。