摘要
线粒体疾病是指由线粒体DNA(mtDNA)或核DNA(nDNA)突变引起线粒体代谢酶的功能缺陷导致三磷酸腺苷(ATP)合成障碍、能量产生不足而出现的一组多系统疾病,可单独或同时累及神经、肌肉、眼、耳、消化、内分泌、心血管、肾脏及血液系统等。mtDNA的遗传特性是非常复杂的,因为每个细胞中都会有多个mtDNA的拷贝,mtDNA的突变可以是同质的(基本上所有的mtDNA都是突变型),也可以是异质的(混合了突变和野生型的mtDNA),只有当突变型mtDNA所占比例达到临界阈值时才会出现功能障碍。线粒体疾病不仅可以发生在任何年龄段,而且可以在任何器官系统中引起症状。因此,探索相关的临床治疗方法具有重大意义。新一代生物技术催生了针对线粒体基因组突变导致的线粒体疾病的治疗思路和方法,本文总结了处于研究阶段的相关的探索性研究工作,并提出了相关的治疗瓶颈问题,为研发线粒体疾病治疗新方法提供参考。
Mitochondrial diseases refer to a group of multi-system diseases caused by mitochondrial DNA(mtDNA)or nuclear DNA(nDNA)mutations that cause functional defects of mitochondrial metabolic enzymes,leading to adenosine triphosphate(ATP)synthesis disorders and insufficient energy production.It can involve nerves,muscles,eyes,ears,digestion,endocrine,cardiovascular,kidney and blood system alone or simultaneously.The genetic properties of mtDNA are very complex because there are multiple copies of mtDNA in each cell,and mtDNA mutations can be homogeneous(basically all mtDNA is a mutant)or heterogeneous(a mixture of mutated and wild-type mtDNA).Dysfunction occurs only when the proportion of mutant mtDNA reaches a critical threshold.Not only can mitochondrial diseases occur at any age,but they can cause symptoms in any organ system.Therefore,it is of great significance to study gene therapy for mitochondrial diseases.The new generation of biotechnology has given birth to the treatment ideas and methods for mitochondrial diseases caused by mitochondrial genome mutations.In the present paper,we summarize the clinical application and the related exploratory research work in the research stage and highlight the bottlenecks for the treatments.It may pave a way for the development of novel therapeutic methods for mitochondrial diseases.
作者
杨振
任凯群
谷峰
YANG Zhen;RENG Kaiqun;GU Feng(The Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province,School of Medicine,Hunan Normal University,Changsha 410013,China;Guangxiu Hospital Affiliated with Hunan Normal University/Hunan Guangxiu Hospital,Changsha 410205,China)
出处
《晓庄学院学报（医学版）》
2023年第5期1-7,共7页
Journal of Hunan Normal University(Medical Sciences)
基金
国家自然科学基金项目(82271910)
关键词
线粒体疾病
基因编辑
基因治疗
mitochondrial diseases
gene editing
gene therapy
