Gene therapy strategies for rare monogenic disorders with nuclear or mitochondrial gene mutations

• Published in: Biomaterials Vol. 277; p. 121108
• Main Authors: Wang, Yi, Hu, Li-Fan, Zhou, Tian-Jiao, Qi, Lian-Yu, Xing, Lei, Lee, Jaiwoo, Wang, Feng-Zhen, Oh, Yu-Kyoung, Jiang, Hu-Lin
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01.10.2021
• Subjects: Gene delivery systems; Gene editing; Gene therapy; Rare monogenic disorders; Gene delivery systems; Rare monogenic disorders; Gene therapy; Gene editing
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2021.121108

Rare monogenic disorders are a group of single-gene-mutated diseases that have a low incidence rate (less than 0.5‰) and eventually lead to patient disability and even death. Due to the relatively low number of people affected, these diseases typically fail to attract a great deal of commercial investment and research interest, and the affected patients thus have unmet medical needs. Advances in genomics biology, gene editing, and gene delivery can now offer potentially effective options for treating rare monogenic diseases. Herein, we review the application of gene therapy strategies (traditional gene therapy and gene editing) against various rare monogenic diseases with nuclear or mitochondrial gene mutations, including eye, central nervous system, pulmonary, systemic, and blood cell diseases. We summarize their pathologic features, address the barriers to gene delivery for these diseases, discuss available therapies in the clinic and in clinical trials, and sum up in-development gene delivery systems for various rare monogenic disorders. Finally, we elaborate the possible directions and outlook of gene therapy for rare monogenic disorders. •For several rare genetic disorders, there are clinically unmet needs.•Gene therapy could be an effective strategy to treat such genetic disorders.•Viral and nonviral vectors are used for delivering genes to eye, central nervous system, lung, and blood cells.•Depending on the target tissues of a given genetic disorder, viral or nonviral delivery strategies must be optimized.