CRISPR/Cas9系统已经彻底改革了基因编辑领域，使之变得可能，在人类基因组中高精度地中断、插入或替换感兴趣的序列。其简易的设计和广泛的适用性为治疗遗传性疾病开辟了多种治疗替代方案。确确实实，在最近几年中，基于造血干细胞的自我更新和多能分化特性，已经发展出了非常有前途的用于纠正血液学疾病的方法，使这个细胞亚集成为生物技术治疗的理想目标。这种技术已经应用于不同的先天性血液疾病，如原发性免疫功能不足、X-连锁严重综合征、X-连锁慢性肉芽肿病或Wiskott-Aldrich综合征，以及遗传性骨髓衰竭综合征，如Fanconi贫血、先天性无巨大核磷体血小板减少症或严重先天性中性粒细胞减少症。此外，CRISPR/Cas9基因编辑已经成功实现了用于癌症免疫疗法的新疗法，通过开发有前途的策略，如使用肿瘤溶解病毒或采用嵌合抗原受体T细胞疗法进行细胞转移。因此，考虑到不同基因和突变的多样性，我们可以通过CRISPR/Cas9以不同的方式利用不同的DNA修复机制，从同源修复到非同源端联接，再到最新的技术如碱基和质量编辑。虽然造血干细胞中的输送系统仍然是这种技术的瓶颈，但这次评论中显示的某些基因组编辑进展已经达到了临床阶段，并显示出非常有前途的初步结果。版权©2022国际细胞和基因治疗学会。由Elsevier Inc.发表。保留所有权利。

The clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system has revolutionized the gene editing field, making it possible to interrupt, insert or replace a sequence of interest with high precision in the human genome. Its easy design and wide applicability open up a variety of therapeutic alternatives for the treatment of genetic diseases. Indeed, very promising approaches for the correction of hematological disorders have been developed in the recent years, based on the self-renewal and multipotent differentiation properties of hematopoietic stem and progenitor cells, which make this cell subset the ideal target for gene therapy purposes. This technology has been applied in different congenital blood disorders, such as primary immunodeficiencies, X-linked severe combined immunodeficiency, X-linked chronic granulomatous disease or Wiskott-Aldrich syndrome, and inherited bone marrow failure syndromes, such as Fanconi anemia, congenital amegakaryocytic thrombocytopenia or severe congenital neutropenia. Furthermore, CRISPR/Cas9-based gene editing has been implemented successfully as a novel therapy for cancer immunotherapy, by the development of promising strategies such as the use of oncolytic viruses or adoptive cellular therapy to the chimeric antigen receptor-T-cell therapy. Therefore, considering the variety of genes and mutations affected, we can take advantage of the different DNA repair mechanisms by CRISPR/Cas9 in different manners, from homology-directed repair to non-homologous-end-joining to the latest emerging technologies such as base and prime editing. Although the delivery systems into hematopoietic stem and progenitor cells are still the bottleneck of this technology, some of the advances in genome editing shown in this review have already reached a clinical stage and show very promising preliminary results.Copyright © 2022 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.