线粒体单基因突变罕见病的基因治疗研究进展  

Advances in Research on Gene Therapeutics for Rare Diseases with Mitochondrial Monogenic Mutation

作　　者：刘娜辉 王译 邢磊 姜虎林 LIU Nahui;WANG Yi;XING Lei;JIANG Hulin(School of Pharmacy,China Pharmaceutical University,Nanjing 210009,China)

机构地区：[1]中国药科大学药学院,江苏南京210009

出　　处：《药学进展》2022年第11期804-812,共9页Progress in Pharmaceutical Sciences

摘　　要：线粒体单基因突变罕见病是一组由单个线粒体基因突变而引发的疾病,具有病情严重、诊断困难、治愈率低等特点;其中有些疾病甚至会致残致死,给家庭和社会带来了沉重的负担。目前,小分子药物在线粒体单基因突变罕见病的大多数治疗策略中仍占据主导地位,但由于小分子药物仅能缓解疾病症状,无法改变线粒体基因突变所导致的问题,因此,众多患者仍然面临无药可治的困难境地。近年来,基因组生物学、基因编辑和基因递送系统的发展给线粒体单基因突变罕见病的治疗带来了希望。以2个具有代表性的线粒体单基因突变罕见病为例,归纳了其病理特征、基因递送屏障和临床试验中使用的治疗方法,并总结了针对该类疾病已开发的基因递送系统。最后,对基因疗法治疗线粒体单基因突变罕见病所面临的挑战和应用前景进行了系统的讨论。Rare diseases with mitochondrial monogenic mutation are a group of diseases caused by mutations in a single mitochondrial gene. They are characterized by severe disease, difficult diagnosis and low cure rate. Some of these diseases can even lead to disability and death, imposing a heavy burden on families and society. Currently, small-molecule drugs still dominate most of the treatment strategies for these rare diseases with mitochondrial monogenic mutation. However, such small-molecule drugs generally only relieve the symptoms of these disorders and cannot fundamentally solve the problem. Therefore, the affected patients still have unmet medical needs. In recent years,the development of genomics biology, gene editing, and gene delivery systems has brought hope for the treatment of rare diseases with mitochondrial monogenic mutation. Taking two representative rare diseases with mitochondrial monogenic mutation as examples, we have summarized their pathologic features, gene delivery barriers, and therapeutic methods used in clinical trials, as well as the gene delivery systems that has been developed for these diseases in this article. Finally, we systematically discussed the challenges and application prospects of gene therapy for the treatment of rare diseases with mitochondrial monogenic mutation.

关 键 词：线粒体单基因突变罕见病 基因治疗 非病毒载体 病毒载体 

分 类 号：R945[医药卫生—微生物与生化药学]