CRISPR-Cas9基因编辑技术在范可尼贫血中的研究进展  

Advancements in CRISPR-Cas9 for Fanconi anemia

作　　者：高怡曼 常丽贤 竺晓凡 Gao Yiman;Chang Lixian;Zhu Xiaofan(State Key Laboratory of Experimental Hematology,National Clinical Research Center for Blood Diseases,Haihe Laboratory of Cell Ecosystem,Institute of Hematology&Blood Diseases Hospital,Chinese Academy of Medical Sciences&Peking Union Medical College,Tianjin 300020,China;Tianjin Institutes of Health Science,Tianjin 301600,China)

机构地区：[1]中国医学科学院血液病医院(中国医学科学院血液学研究所),血液与健康全国重点实验室,国家血液系统疾病临床医学研究中心,细胞生态海河实验室,天津300020 [2]天津医学健康研究院,天津301600

出　　处：《中华血液学杂志》2025年第3期276-280,共5页Chinese Journal of Hematology

基　　金：国家自然科学基金(82270144);中国医学科学院医学与健康科技创新工程项目(2022-I2M-1-022)。

摘　　要：范可尼贫血(FA)是一种以基因组不稳定和对DNA交联剂敏感为特征的遗传性骨髓衰竭综合征。近年来,CRISPR-Cas9技术在FA的基因治疗领域取得了突破性进展。传统CRISPR-Cas9技术在FA基因编辑中已得到成功应用,单碱基编辑技术基于CRISPR/Cas9系统,能够对FA患者中常见的基因突变进行精准、高效的基因修复;尽管引导编辑技术提供了新的基因编辑可能性,但目前在FA中的应用尚未开展。FA基因编辑技术虽取得了显著进步,但仍面临诸多挑战,包括收集足够的造血干细胞、基因编辑后增加肿瘤发生风险、染色体不稳定、脱靶效应等。未来研究应聚焦在优化单链向导RNA和Cas9核酸酶、设计更严格的PAM序列方式等减少脱靶效应,设计个性化的基因编辑策略。伦理与监管问题和长期随访同样也是今后开展基因编辑工作的重点。随着技术的不断进步和临床试验的深入,我们有望在未来看到CRISPR-Cas9技术在FA治疗中取得更多的突破。本文就常用的CRISPR技术在FA治疗领域的最新研究进展展开综述,并分析了该技术在FA基因治疗中的优势与挑战。Fanconi anemia(FA)is a hereditary bone marrow failure syndrome that is characterized by genomic instability and heightened sensitivity to DNA cross-linking agents.In recent years,the CRISPR-Cas9 technology has exhibited groundbreaking progress in the field of gene therapy for FA.The traditional CRISPR-Cas9 technology has been successfully applied in FA gene editing.Further,single-base editing technology,based on the CRISPR/Cas9 system,performs precise and efficient gene repair for prevalent gene mutations in patients with FA.The prime editing technology provides new possibilities for gene editing;however,its application in FA has not been initiated.Despite significant advancements in FA gene editing technology,several challenges remain,including the collection of sufficient hematopoietic stem cells,the risk of increased tumorigenesis postgene editing,chromosomal instability,and off-target effects.Future research is recommended to focus on optimizing sgRNA and Cas9 nucleases,designing stricter PAM sequences to reduce off-target effects,and devising personalized gene editing strategies.Further,ethical and regulatory issues as well as long-term follow-ups are crucial priorities for future gene editing work.With continuous technological advancements and in-depth clinical trials,we expect more breakthroughs in FA treatment using the CRISPR-Cas9 technology in the future.This article reviews the latest research progress of CRISPR technology in FA treatment and analyzes the advantages and disadvantages of this technology in FA gene therapy.

关 键 词：引导编辑 单碱基编辑 范可尼贫血 CRISPR-Cas9 

分 类 号：R55[医药卫生—血液循环系统疾病]