基于CRISPR-Cas13家族的RNA编辑系统及其最新进展

Research Progress on CRISPR-Cas13-mediated RNA Editing System

存在于细菌和古菌中的获得性免疫系统CRISPR-Cas目前已被广泛应用到生物技术领域,尤其是靶向DNA的CRISPR-Cas9技术。然而CRISPR-Cas系统靶向RNA的技术还处于初步应用阶段。Ⅵ型CRISPR-Cas系统(CRISPR-Cas13)的发现,揭示了RNA引导的RNA靶向性。CRISPR-Cas13是目前CRISPR-Cas家族中唯一只靶向ssRNA的系统,为RNA靶向和RNA编辑奠定了基础。根据Cas13系统发育已证明将Ⅵ型CRISPR-Cas系统分为4种亚型(A-D)。主要对目前最新的靶向RNA技术的CRISPR-Cas13家族的分类以及防御机制进行了综述,介绍了CRISPR-Cas13技术的应用以及基于CRISPR-Cas13家族的RNA编辑系统的最新研究进展。最后,对目前CRISPR-Cas13 RNA编辑技术体系存在的问题进行了分析和对未来的发展进行展望。

The immune defense system CRISPR-Cas,which is universal in bacteria and archaea,has now been extensively used in the field of biotechnology,especially CRISPR-Cas9 for targeting DNA.However,the RNA-targeted CRISPR-Cas technology is still in the preliminary application stage.The discovery of VI-type CRISPR-Cas system(CRISPR-Cas13)reveals RNA-guided RNA targeting.CRISPRCas13 is the system in the CRISPR-Cas family that targets only ssRNA so far,which lays a foundation for RNA targeting and RNA editing.It has recently been demonstrated that VI-type CRISPR-Cas system can be divided into 4 subtypes(A-D)based on Cas13 phylogeny.Here we review the classification and defense mechanisms of the latest RNA-targeting CRISPR-Cas13 systems,describes the advances in applications of CRISPR-Cas13 systems and in CRISPR-Cas13-mediated RNA editing system,and finally we analyze the remaining questions and highlight the prospects in CRISPR-Cas13-mediated RNA editing system.