Review Article | Published:

Assisted reproductive technologies to prevent human mitochondrial disease transmission

Nature Biotechnology volume 35, pages 10591068 (2017) | Download Citation

Abstract

Mitochondria are essential cytoplasmic organelles that generate energy (ATP) by oxidative phosphorylation and mediate key cellular processes such as apoptosis. They are maternally inherited and in humans contain a 16,569-base-pair circular genome (mtDNA) encoding 37 genes required for oxidative phosphorylation. Mutations in mtDNA cause a range of pathologies, commonly affecting energy-demanding tissues such as muscle and brain. Because mitochondrial diseases are incurable, attention has focused on limiting the inheritance of pathogenic mtDNA by mitochondrial replacement therapy (MRT). MRT aims to avoid pathogenic mtDNA transmission between generations by maternal spindle transfer, pronuclear transfer or polar body transfer: all involve the transfer of nuclear DNA from an egg or zygote containing defective mitochondria to a corresponding egg or zygote with normal mitochondria. Here we review recent developments in animal and human models of MRT and the underlying biology. These have led to potential clinical applications; we identify challenges to their technical refinement.

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Change history

  • Corrected online 14 December 2017

    In the version of this article initially published, in Table 2, first column, “m.13095T > C” should have been “m.130bT > C,” where “b” refers to the footnote “Characters hidden to respect confidentiality,” as with the other three from the Newcastle Group. In addition, the footnote “a” for Table 2 should have read “http://hfeaarchive.uksouth.cloudapp.azure.com/www.hfea.gov.uk/docs/Fourth_scientific_review_mitochondria_2016.pdf” rather than “Personal communication.” The following acknowledgment was omitted: “The authors thank Rob Taylor, Charlotte Alston, Emma Watson, Sam Byerley, Jane Stewart and Robert McFarland (Wellcome Centre for Mitochondrial Research Newcastle University and Newcastle upon Tyne Hospitals NHS Foundation Trust) for unpublished data included in Table 2.” The errors have been corrected in the HTML and PDF versions of the article.

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Acknowledgements

A.C.F.P. is grateful for support from the Medical Research Council, UK (grants MR/N000080/1 and MR/N020294/1). The authors thank Rob Taylor, Charlotte Alston, Emma Watson, Sam Byerley, Jane Stewart and Robert McFarland (Wellcome Centre for Mitochondrial Research Newcastle University and Newcastle upon Tyne Hospitals NHS Foundation Trust) for unpublished data included in Table 2.

Author information

Affiliations

  1. MRC Harwell Institute, Mammalian Genetics Unit, Harwell Campus, Harwell, Oxfordshire, UK.

    • Andy Greenfield
  2. Division of Women's Health, King's College, London, UK.

    • Peter Braude
  3. Clinical Genetics Department, Guy′s Hospital, Great Maze Pond, London, UK.

    • Frances Flinter
  4. The Francis Crick Institute, London, UK.

    • Robin Lovell-Badge
  5. Genetics Department, Guy's & St Thomas' NHS Foundation Trust and Division of Women's Health, King's College, London, UK.

    • Caroline Ogilvie
  6. Laboratory of Mammalian Molecular Embryology, Department of Biology and Biochemistry, University of Bath, Bath, UK.

    • Anthony C F Perry

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The authors declare no competing financial interests.

Corresponding author

Correspondence to Andy Greenfield.

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DOI

https://doi.org/10.1038/nbt.3997