Yonsei University College of Medicine, Seoul, 03722, Republic of Korea.
Department of Pharmacology, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea.
Hum Genet. 2019 Jun;138(6):563-590. doi: 10.1007/s00439-019-02028-2. Epub 2019 May 21.
Since its discovery, the Clustered Regularly Interspaced Short Palindromic Repeat (the CRISPR) system has been increasingly applied to therapeutic genome editing. Employment of several viral and non-viral vectors has enabled efficient delivery of the CRISPR system to target cells or tissues. In addition, the CRISPR system is able to modulate the target gene's expression in various ways, such as mutagenesis, gene integration, epigenome regulation, chromosomal rearrangement, base editing and mRNA editing. However, there are still limitations hindering an ideal application of the system: inefficient delivery, dysregulation of the delivered gene, the immune response against the CRISPR system, the off-target effects or the unintended on-target mutations. In addition, there are recent discoveries that have not been yet applied to CRISPR-mediated therapeutic genome editing. Here, we review the overall principles related to the therapeutic application of the CRISPR system, along with new strategies for the further application and prospects to overcome the limitations.
自发现以来，成簇规律间隔短回文重复序列（CRISPR）系统已越来越多地应用于治疗性基因组编辑。几种病毒和非病毒载体的应用使 CRISPR 系统能够有效地将其递送至靶细胞或组织。此外，CRISPR 系统能够以多种方式调节靶基因的表达，如诱变、基因整合、表观基因组调控、染色体重排、碱基编辑和 mRNA 编辑。然而，仍存在一些限制因素阻碍了该系统的理想应用：递送效率低、递送基因失调、对 CRISPR 系统的免疫反应、脱靶效应或意外的靶上突变。此外，最近还有一些尚未应用于 CRISPR 介导的治疗性基因组编辑的发现。在这里，我们综述了 CRISPR 系统治疗应用的总体原则，以及进一步应用的新策略和克服限制的前景。
