The potential of mitochondrial genome engineering

Nat Rev Genet. 2022 Apr;23(4):199-214. doi: 10.1038/s41576-021-00432-x. Epub 2021 Dec 2.

Abstract

Mitochondria are subject to unique genetic control by both nuclear DNA and their own genome, mitochondrial DNA (mtDNA), of which each mitochondrion contains multiple copies. In humans, mutations in mtDNA can lead to devastating, heritable, multi-system diseases that display different tissue-specific presentation at any stage of life. Despite rapid advances in nuclear genome engineering, for years, mammalian mtDNA has remained resistant to genetic manipulation, hampering our ability to understand the mechanisms that underpin mitochondrial disease. Recent developments in the genetic modification of mammalian mtDNA raise the possibility of using genome editing technologies, such as programmable nucleases and base editors, for the treatment of hereditary mitochondrial disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • DNA, Mitochondrial / genetics
  • Genome, Mitochondrial*
  • Humans
  • Mammals / genetics
  • Mitochondria / genetics
  • Mitochondrial Diseases* / genetics
  • Mitochondrial Diseases* / therapy
  • Mutation

Substances

  • DNA, Mitochondrial