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

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.