Chernega Timofei, Choi Jaehyoung, Salmena Leonardo, Andreazza Ana Cristina
Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON M5S 1A8, Canada.
Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada.
Mol Ther Nucleic Acids. 2022 Oct 27;30:359-377. doi: 10.1016/j.omtn.2022.10.012. eCollection 2022 Dec 13.
Mitochondrial diseases are one of the largest groups of neurological genetic disorders. Despite continuous efforts of the scientific community, no cure has been developed, and most treatment strategies rely on managing the symptoms. After the success of coronavirus disease 2019 (COVID-19) mRNA vaccines and accelerated US Food and Drug Administration (FDA) approval of four new RNAi drugs, we sought to investigate the potential of mitochondrion-targeting RNA-based therapeutic agents for treatment of mitochondrial diseases. Here we describe the causes and existing therapies for mitochondrial diseases. We then detail potential RNA-based therapeutic strategies for treatment of mitochondrial diseases, including use of antisense oligonucleotides (ASOs) and RNAi drugs, allotopic therapies, and RNA-based antigenomic therapies that aim to decrease the level of deleterious heteroplasmy in affected tissues. Finally, we review different mechanisms by which RNA-based therapeutic agents can be delivered to the mitochondrial matrix, including mitochondrion-targeted nanocarriers and endogenous mitochondrial RNA import pathways.
线粒体疾病是最大的神经遗传疾病群体之一。尽管科学界不断努力，但尚未开发出治愈方法，大多数治疗策略都依赖于症状管理。在2019冠状病毒病（COVID-19）mRNA疫苗取得成功以及美国食品药品监督管理局（FDA）加速批准四种新型RNA干扰（RNAi）药物之后，我们试图研究靶向线粒体的RNA治疗剂治疗线粒体疾病的潜力。在此，我们描述线粒体疾病的病因和现有疗法。然后，我们详细介绍治疗线粒体疾病的潜在RNA治疗策略，包括使用反义寡核苷酸（ASO）和RNAi药物、异位疗法以及旨在降低受影响组织中有害异质性水平的基于RNA的反基因组疗法。最后，我们综述基于RNA的治疗剂递送至线粒体基质的不同机制，包括靶向线粒体的纳米载体和内源性线粒体RNA导入途径。
Zotero 插件
