Fixing the powerhouse: genetic engineering of mitochondrial DNA

Abstract

Mitochondria are complex factories that provide our cells with most of the energy we need to survive and perform daily tasks. They comprise their own small genome, mitochondrial DNA (mtDNA), which contains genes for parts of the energy-producing machinery. Mutations in mtDNA can lead to mitochondrial diseases, which are a devastating group of heterogenous inheritable diseases that can develop at any stage of life. Despite rapid developments in genome engineering for nuclear DNA, the incompatibility of certain techniques in mitochondria has meant that the field of mitochondrial genome modification has been impeded for many years. However, recent advances in mtDNA engineering techniques, such as programmable nucleases and base editors, will allow for a deeper understanding of the processes taking place in mitochondria and improve the prospects of developing treatments for mitochondrial diseases.