Challenges of mitochondrial DNA editing in mammalian cells: focus on treatment of cardiovascular disease

Abstract

Atherosclerosis is the major cause of occurrence and development of cardiovascular disease. Mutations in mitochondrial DNA (mtDNA) can lead to the development of several pathologies. Over the last few years, there has been increasing evidence that mitochondrial dysfunction caused by mtDNA mutations is associated with atherogenesis and other diseases of the cardiovascular system. Several therapeutic approaches have been developed for the improvement of mitochondrial function, and they are mainly associated with the cellular and tissue antioxidant defense system. However, these approaches are not targeted at mtDNA mutations, which trigger the pathogenesis of disease. Gene-editing technologies could be a promising approach for the treatment of cardiovascular disease caused by mtDNA mutations. To date, such technologies have shown considerable success in mitochondrial gene editing in cell and animal models. Gene-editing technologies allow the determination of the role of mitochondrial genome mutations in the development and complication of various chronic diseases. Nevertheless, further investigation and optimization in this field is required for future human trials. This review highlights the progress and existing challenges of modern technologies and approaches to mitochondrial gene editing.

Fish Models for Exploring Mitochondrial Dysfunction Affecting Neurodegenerative Disorders

“…The mito-CRISPR/Cas9 system was also successfully used in the knock-in strategy in the zebrafish model [ 261 ]. However, these strategies face difficulty in delivering the editing components into mitochondria [ 262 ]. In addition, mitochondria-targeted nucleases selectively reduced mtDNA haplotypes in the germline, eliminating mitochondrial mutations [ 263 , 264 ].…”