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Therapeutic Manipulation of mtDNA Heteroplasmy: A Shifting Perspective

Lookup NU author(s): Emeritus Professor Doug Turnbull



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2020 Elsevier Ltd. Mutations of mitochondrial DNA (mtDNA) often underlie mitochondrial disease, one of the most common inherited metabolic disorders. Since the sequencing of the human mitochondrial genome and the discovery of pathogenic mutations in mtDNA more than 30 years ago, a movement towards generating methods for robust manipulation of mtDNA has ensued, although with relatively few advances and some controversy. While developments in the transformation of mammalian mtDNA have stood still for some time, recent demonstrations of programmable nuclease-based technology suggest that clinical manipulation of mtDNA heteroplasmy may be on the horizon for these largely untreatable disorders. Here we review historical and recent developments in mitochondrially targeted nuclease technology and the clinical outlook for treatment of hereditary mitochondrial disease.

Publication metadata

Author(s): Jackson CB, Turnbull DM, Minczuk M, Gammage PA

Publication type: Review

Publication status: Published

Journal: Trends in Molecular Medicine

Year: 2020

Volume: 26

Issue: 7

Pages: 698-709

Print publication date: 01/07/2020

Online publication date: 26/03/2020

Acceptance date: 02/04/2018

ISSN (print): 1471-4914

ISSN (electronic): 1471-499X

Publisher: Elsevier Ltd


DOI: 10.1016/j.molmed.2020.02.006