Evidence map›Paper›PMID 27281217›Full record

ArticleNature2016

Towards clinical application of pronuclear transfer to prevent mitochondrial DNA disease.

Louise A Hyslop, Paul Blakeley, Lyndsey Craven, Jessica Richardson, Norah M E Fogarty, Elpida Fragouli, Mahdi Lamb, Sissy E Wamaitha, Nilendran Prathalingam, Qi Zhang and 13 more

Erratum issuedOpen access · greenAbstract read
In one paragraph

Article in Nature, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 150 papers.

0numbers the graph read from it
0cells of the map it votes in
150citing papers in PubMed
25.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

150 citing papers in PubMed, 345 citations in OpenAlex.

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  9. Article
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  13. Observational
  14. Review
  15. Article
  16. Pronuclear Transfer and Maternal Spindle Transfer in the Mouse.Methods in molecular biology (Clifton, N.J.) · 2026
    Article
  17. Mechanistic study on the role of multi-pathway autophagy in ovarian aging: literature review.Apoptosis : an international journal on programmed cell death · 2025
    Review
  18. Review
  19. Article
  20. Article

90 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors at 6 institutions in 1 country.

Louise A HyslopWellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Biomedicine West Wing, Centre for Life, Times Square, Newcastle upon Tyne NE1 3BZ, UK.
Paul BlakeleyThe Francis Crick Institute, Human Embryo and Stem Cell Laboratory, Mill Hill Laboratory, Mill Hill, London NW7 1AA, UK.
Lyndsey CravenWellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience, Newcastle University, The Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.
Jessica RichardsonWellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Biomedicine West Wing, Centre for Life, Times Square, Newcastle upon Tyne NE1 3BZ, UK.
Norah M E FogartyThe Francis Crick Institute, Human Embryo and Stem Cell Laboratory, Mill Hill Laboratory, Mill Hill, London NW7 1AA, UK.
Elpida FragouliReprogenetics UK, Institute of Reproductive Sciences, Oxford Business Park North, Oxford OX4 2HW, UK.
Mahdi LambWellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Biomedicine West Wing, Centre for Life, Times Square, Newcastle upon Tyne NE1 3BZ, UK.
Sissy E WamaithaThe Francis Crick Institute, Human Embryo and Stem Cell Laboratory, Mill Hill Laboratory, Mill Hill, London NW7 1AA, UK.
Nilendran PrathalingamWellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Biomedicine West Wing, Centre for Life, Times Square, Newcastle upon Tyne NE1 3BZ, UK.
Qi ZhangWellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Biomedicine West Wing, Centre for Life, Times Square, Newcastle upon Tyne NE1 3BZ, UK.
Hannah O'KeefeWellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Biomedicine West Wing, Centre for Life, Times Square, Newcastle upon Tyne NE1 3BZ, UK.
Yuko TakedaWellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Biomedicine West Wing, Centre for Life, Times Square, Newcastle upon Tyne NE1 3BZ, UK.
Lucia ArizziWellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Biomedicine West Wing, Centre for Life, Times Square, Newcastle upon Tyne NE1 3BZ, UK.
Samer AlfarawatiReprogenetics UK, Institute of Reproductive Sciences, Oxford Business Park North, Oxford OX4 2HW, UK.
Helen A TuppenWellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience, Newcastle University, The Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.
Laura IrvingWellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Biomedicine West Wing, Centre for Life, Times Square, Newcastle upon Tyne NE1 3BZ, UK.
Dimitrios KalleasWellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Biomedicine West Wing, Centre for Life, Times Square, Newcastle upon Tyne NE1 3BZ, UK.
Meenakshi ChoudharyNewcastle Fertility Centre, Biomedicine West Wing, Centre for Life, Times Square, Newcastle upon Tyne NE1 4EP, UK.
Dagan WellsUniversity of Oxford, Nuffield Department of Obstetrics and Gynaecology, John Radcliffe Hospital, Oxford OX3 9DU, UK.
Alison P MurdochNewcastle Fertility Centre, Biomedicine West Wing, Centre for Life, Times Square, Newcastle upon Tyne NE1 4EP, UK.
Douglass M TurnbullWellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience, Newcastle University, The Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.
Kathy K NiakanThe Francis Crick Institute, Human Embryo and Stem Cell Laboratory, Mill Hill Laboratory, Mill Hill, London NW7 1AA, UK.
Mary HerbertWellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Biomedicine West Wing, Centre for Life, Times Square, Newcastle upon Tyne NE1 3BZ, UK.
Centre for Life · GBWellcome Centre for Mitochondrial Research · GBThe Francis Crick Institute · GBNewcastle University · GBOxford Fertility · GBJohn Radcliffe Hospital · GB

Funding

Cancer Research UKMedical Research Council G0601157Medical Research Council MC_UP_1202/9Medical Research Council MR/J003603/1Medical Research Council MR/L016354/1Wellcome Trust 096919
6 · The paper itself

Abstract

Mitochondrial DNA (mtDNA) mutations are maternally inherited and are associated with a broad range of debilitating and fatal diseases. Reproductive technologies designed to uncouple the inheritance of mtDNA from nuclear DNA may enable affected women to have a genetically related child with a greatly reduced risk of mtDNA disease. Here we report the first preclinical studies on pronuclear transplantation (PNT). Surprisingly, techniques used in proof-of-concept studies involving abnormally fertilized human zygotes were not well tolerated by normally fertilized zygotes. We have therefore developed an alternative approach based on transplanting pronuclei shortly after completion of meiosis rather than shortly before the first mitotic division. This promotes efficient development to the blastocyst stage with no detectable effect on aneuploidy or gene expression. After optimization, mtDNA carryover was reduced to <2% in the majority (79%) of PNT blastocysts. The importance of reducing carryover to the lowest possible levels is highlighted by a progressive increase in heteroplasmy in a stem cell line derived from a PNT blastocyst with 4% mtDNA carryover. We conclude that PNT has the potential to reduce the risk of mtDNA disease, but it may not guarantee prevention.

Indexed as

Nuclear Transfer TechniquesAdultBlastocystCell NucleusCytoplasmDNA, MitochondrialFemaleGene Expression ProfilingHumansMaleMeiosisMitochondriaMitochondrial DiseasesMitochondrial Replacement TherapyStem CellsTranslational Research, BiomedicalDNA, Mitochondrial

Identifiers

PMID27281217
PMCPMC5131843
OpenAlexW2412655997

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.