Hille Frank, Charpentier Emmanuelle
Department of Regulation in Infection Biology, Max Planck Institute for Infection Biology, Berlin 10117, Germany.
Department of Regulation in Infection Biology, Max Planck Institute for Infection Biology, Berlin 10117, Germany The Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå Centre for Microbial Research (UCMR), Department of Molecular Biology, Umeå University, Umeå 90187, Sweden
Philos Trans R Soc Lond B Biol Sci. 2016 Nov 5;371(1707). doi: 10.1098/rstb.2015.0496.
Prokaryotes have evolved several defence mechanisms to protect themselves from viral predators. Clustered regularly interspaced short palindromic repeats (CRISPR) and their associated proteins (Cas) display a prokaryotic adaptive immune system that memorizes previous infections by integrating short sequences of invading genomes-termed spacers-into the CRISPR locus. The spacers interspaced with repeats are expressed as small guide CRISPR RNAs (crRNAs) that are employed by Cas proteins to target invaders sequence-specifically upon a reoccurring infection. The ability of the minimal CRISPR-Cas9 system to target DNA sequences using programmable RNAs has opened new avenues in genome editing in a broad range of cells and organisms with high potential in therapeutical applications. While numerous scientific studies have shed light on the biochemical processes behind CRISPR-Cas systems, several aspects of the immunity steps, however, still lack sufficient understanding. This review summarizes major discoveries in the CRISPR-Cas field, discusses the role of CRISPR-Cas in prokaryotic immunity and other physiological properties, and describes applications of the system as a DNA editing technology and antimicrobial agent.This article is part of the themed issue 'The new bacteriology'.
原核生物已经进化出多种防御机制来保护自己免受病毒捕食者的侵害。成簇规律间隔短回文重复序列（CRISPR）及其相关蛋白（Cas）构成了一种原核生物适应性免疫系统，该系统通过将入侵基因组的短序列（称为间隔序列）整合到CRISPR基因座中来记忆先前的感染。与重复序列间隔排列的间隔序列被表达为小向导CRISPR RNA（crRNA），在再次感染时，Cas蛋白利用这些crRNA对入侵者进行序列特异性靶向。最小的CRISPR-Cas9系统利用可编程RNA靶向DNA序列的能力，为广泛细胞和生物体中的基因组编辑开辟了新途径，在治疗应用方面具有很高潜力。虽然众多科学研究已经阐明了CRISPR-Cas系统背后的生化过程，但免疫步骤的几个方面仍缺乏足够的了解。本综述总结了CRISPR-Cas领域的主要发现，讨论了CRISPR-Cas在原核生物免疫及其他生理特性中的作用，并描述了该系统作为一种DNA编辑技术和抗菌剂的应用。本文是主题为“新细菌学”的特刊的一部分。
