文献综述

MUT型甲基丙二酸血症基因治疗研究进展

  • 丁一 ,
  • 于玥 综述 ,
  • 韩连书 审校
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  • 上海交通大学医学院附属新华医院 上海市儿科医学研究所儿内分泌遗传代谢科(上海 200092)

收稿日期: 2024-03-25

  网络出版日期: 2024-12-02

Research progress in gene therapy for MUT-type methylmalonic acidemia

  • Yi Reviewer: DING ,
  • Yue YU ,
  • Lianshu Reviser: HAN
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  • Department of Pediatric Endocrinology and Genetic Metabolism, Shanghai Institute for Pediatric Research, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China

Received date: 2024-03-25

  Online published: 2024-12-02

摘要

MUT型甲基丙二酸血症(MMA)是由MMUT基因变异引起的常染色体隐性遗传病,可涉及多脏器损害,以脑损伤为主,死亡率较高。MUT型MMA目前治疗主要包括饮食治疗、左卡尼汀及维生素B12药物治疗,部分严重患者需要肝肾移植,但上述治疗效果不佳,患者预后较差。近几年,在MUT型MMA小鼠模型中已利用腺病毒载体、慢病毒载体、基因编辑、mRNA非病毒载体进行基因治疗及Ⅰ/Ⅱ期临床试验。目前相关临床试验尚处于研发早期,基因治疗有望成为MUT型MMA新治疗方法。文章对MUT型MMA基因治疗研究现状进行系统总结,为后续研究提供参考。

本文引用格式

丁一 , 于玥 综述 , 韩连书 审校 . MUT型甲基丙二酸血症基因治疗研究进展[J]. 临床儿科杂志, 2024 , 42(12) : 1051 -1055 . DOI: 10.12372/jcp.2024.24e0274

Abstract

MUT-type methylmalonic acidemia (MMA) is an autosomal monogenic genetic disorder caused by mutations in the MMUT gene, which can involve multiple organ damage, mainly brain damage, and has a high mortality rate. Diet therapy, levocarnitine and vitamin B12 therapy are the main treatment method for MUT-type MMA, and some severe patients need liver and kidney transplantation, but the treatment effect and prognosis are poor. Gene therapy for MUT-type MMA using various vectors in animal model and phase 1/2 study are underway. Gene therapy in MUT-type MMA clinical trials is still in an early stage and provides a new treatment method. This article reviews the current status of gene therapy research for MUT-type MMA and aims to guide future research.

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