单基因遗传病的治疗

摘要/Abstract

摘要： 单基因遗传病是指由一对等位基因控制的遗传病。目前已知的单基因遗传病超过6000种。虽然每一种单基因遗传病的发病率很低（大多属于罕见病的范畴），但因其种类众多，总体患病率较高。很多单基因遗传病的临床症状亦较严重，甚至导致患者死亡，因此单基因遗传病的治疗对于缓解临床症状、提升患者生活质量至关重要。根据症状和致病机制的不同，对不同单基因遗传病的治疗方式也不尽相同。本研究从蛋白质（包括生物制剂靶向治疗、老药新用、小分子治疗以及蛋白质替代治疗）、基因（体外基因治疗和体内基因治疗）、RNA（ASO疗法、siRNA疗法、miRNA疗法、外显子跳读疗法、tRNA疗法和mRNA疗法）和细胞（造血干细胞移植、干细胞治疗和免疫细胞治疗）4个层面梳理总结现有的单基因遗传病的治疗方法、临床进展，对比不同治疗方法的优势和局限，提出目前单基因遗传病的治疗方式主要集中在蛋白质层面，而基因和RNA层面的治疗方法价格昂贵，并且只有少数疾病获得批准。细胞层面的治疗则大多仍处于临床前研究阶段，应用于临床服务患者仍然任重道远，还有很多科学问题亟待研究与解决。建议在单基因遗传病临床治疗方式的选择上仍需要谨慎考虑其疗效与风险。

关键词: font-size:medium, ">单基因遗传病；蛋白质；基因；RNA；细胞

Abstract: Monogenic diseases are genetic disorders determined by the alleles at a single locus， and more than 6000 monogenic diseases have been identified until now. Although the prevalence of each monogenic disease is low (most are rare diseases)， the overall prevalence is high due to the wide variety of monogenic diseases. Many monogenic diseases have severe clinical symptoms， and even lead to death. Therefore， the treatment of monogenic diseases is very important to relieve clinical symptoms and improve the quality of life of the patients. The treatment of different monogenic diseases varies according to different symptoms and pathogenesis. This study summarized the existing therapeutic methods and clinical progress of monogenic diseases from four levels： protein(including targeted therapies with biological agents，drug repurposing，small molecule therapies，and protein replacement therapies)， gene (ex vivo gene therapy and in vivo gene therapy)， RNA (ASO therapy， siRNA therapy， miRNA therapy， exon skipping therapy， tRNA therapy， and mRNA therapy)， and cell (hematopoietic stem cell transplantation， stem cell therapy， and immune cell therapy). The study compared the advantages and limitations of different therapies， and proposed that the current therapies for monogenic diseases are mainly focused on the protein level， whereas therapies at the gene and RNA levels are costly and only approved for a few diseases. Therapies at the cellular level， on the other hand， are still mostly in the preclinical research stage and have a long way to go before they can be used in the clinic， and there are still a lot of scientific issues that need to be researched and solved. It is recommended that the choice of clinical treatment for monogenic diseases should be carefully considered in terms of efficacy and risk.

Key words: font-size:medium, ">Monogenic diseases； Protein； Gene； RNA； Cell

中图分类号:

王金博, 张嘉会, 周青, 王宇沙. 单基因遗传病的治疗[J]. 中国医药导刊, 2023, 25(7): 661-668.

WANG Jinbo, ZHANG Jiahui, ZHOU Qing, WANG Yusha. The Treatment of Monogenic Diseases[J]. CHINESE JOURNAL OF MEDICINAL GUIDE, 2023, 25(7): 661-668.

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