Assisted reproductive technologies to prevent human mitochondrial disease transmission

A. Greenfield, P. Braude, F. Flinter, Robin Lovell-Badge, C. Ogilvie, Anthony Perry

Research output: Contribution to journalArticle

21 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)1059-1068
Number of pages10
JournalNature Biotechnology
Volume35
Early online date9 Nov 2017
DOIs
Publication statusPublished - 14 Dec 2017

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Mitochondrial Diseases
Assisted Reproductive Techniques
Mitochondria
Mitochondrial DNA
Zygote
Oxidative Phosphorylation
Ovum
Gene encoding
Adenosinetriphosphate
Pathology
Cell death
Polar Bodies
Muscle
Brain
Animals
DNA
Genes
Base Pairing
Organelles
Tissue

Cite this

Assisted reproductive technologies to prevent human mitochondrial disease transmission. / Greenfield, A.; Braude, P.; Flinter, F.; Lovell-Badge, Robin; Ogilvie, C.; Perry, Anthony.

In: Nature Biotechnology, Vol. 35, 14.12.2017, p. 1059-1068.

Research output: Contribution to journalArticle

Greenfield, A, Braude, P, Flinter, F, Lovell-Badge, R, Ogilvie, C & Perry, A 2017, 'Assisted reproductive technologies to prevent human mitochondrial disease transmission', Nature Biotechnology, vol. 35, pp. 1059-1068. https://doi.org/10.1038/nbt.3997
Greenfield, A. ; Braude, P. ; Flinter, F. ; Lovell-Badge, Robin ; Ogilvie, C. ; Perry, Anthony. / Assisted reproductive technologies to prevent human mitochondrial disease transmission. In: Nature Biotechnology. 2017 ; Vol. 35. pp. 1059-1068.
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