Therapeutic potential of engineering the mitochondrial genome

Abstract

Mitochondrial diseases are a group of clinical disorders caused by mutations in the genes encoded by either the nuclear or the mitochondrial genome involved in mitochondrial oxidative phosphorylation. Disorders become evident when mitochondrial dysfunction reaches a cell-specific threshold. Similarly, the severity of disorders is related to the degree of gene mutation. Clinical treatments for mitochondrial diseases mainly rely on symptomatic management. Theoretically, replacing or repairing dysfunctional mitochondria to acquire and preserve normal physiological functions should be effective. Significant advances have been made in gene therapies, including mitochondrial replacement therapy, mitochondrial genome manipulation, nuclease programming, mitochondrial DNA editing, and mitochondrial RNA interference. In this paper, we review the recent progress in these technologies by focusing on advancements that overcome limitations.

Keywords: Embryonic stem cell; Mitochondrial disorders; Mitochondrial replacement therapy; Programmable nucleases; mtDNA editing; mtDNA mutation.