基因编辑在转甲状腺素蛋白淀粉样变心肌病治疗中的进展  

Advance in the gene editing in the treatment of transthyretin cardiac amyloidosis

作　　者：谢林峰 罗素新[1] 黄毕 XIE Lin-feng;LUO Su-xin;HUANG Bi(Department of Cardiology,The First Affiliated Hospital of Chongqing Medical University,Chongqing 400700,China)

机构地区：[1]重庆医科大学附属第一医院心血管内科,重庆市400700

出　　处：《中国心血管病研究》2024年第3期237-241,共5页Chinese Journal of Cardiovascular Research

基　　金：重庆英才计划项目(cstc2022ycjh-bgzxm0231);重庆医科大学未来医学青年创新团队支持计划(0184)。

摘　　要：转甲状腺素蛋白淀粉样变心肌病(ATTR-CM)是由于不溶性转甲状腺素(TTR)蛋白在心肌中沉积引起包括心脏传导异常以及心力衰竭等在内的多种并发症。既往对ATTR-CM的治疗只针对ATTR-CM的并发症如心力衰竭、心律失常等进行治疗,缺乏针对病因治疗的有效药物。近年来,随着TTR的稳定剂如氯苯唑酸及RNA干扰(SiRNA)药物如patisiran等问世,使ATTR-CM的治疗真正进入了病因治疗的时代。基因组编辑技术是有别于传统药物治疗机制的新方法,是通过CRISPR/Cas9工具对目标基因编辑,从而实现从蛋白到临床表型的改变。在ATTR-CM的小动物模型中已证实,通过CRISPR/Cas9基因编辑可有效降低TTR蛋白在组织中的沉积。小样本的临床研究也取得了和动物实验相似的结果,可能为未来ATTR-CM的治疗带来革命性影响。本文对目前基因编辑技术治疗ATTR-CM的进展作一综述。Transthyretin cardiac amyloidosis(ATTR-CM)is caused by the deposition of insoluble transthyroxine(TTR)protein in the myocardium,leading to various complications including cardiac conduction abnormalities and heart failure.In the past,the treatment of ATTR-CM only focused on its complications such as heart failure and arrhythmia,lacking effective drugs for etiology.In recent years,with the emergence of stabilizers for TTR such as tafamidis acid and RNA interference(SiRNA)drugs such as patisiran,the treatment of ATTR-CM has truly entered the era of etiological treatment.Gene editing is a new method that differs from traditional drug therapy mechanisms.It uses CRISPR/Cas9 to edit target genes and achieves the change from protein to clinical phenotype.It has been confirmed in the animal model of ATTR-CM that CRISPR/Cas9 gene editing can effectively reduce the deposition of TTR protein in tissues.Clinical studies on small samples have also achieved similar results as animal experiments,which may have a revolutionary impact on the treatment of ATTR-CM in the future.This article provides a review of the current progress in gene editing technology for the treatment of ATTR-CM.

关 键 词：转甲状腺素蛋白淀粉样变心肌病 心力衰竭 心律失常 基因编辑 

分 类 号：R542.2[医药卫生—心血管疾病]