Evidence map›Paper›PMID 27919073›Full record

ArticleNature2016

Mitochondrial replacement in human oocytes carrying pathogenic mitochondrial DNA mutations.

Eunju Kang, Jun Wu, Nuria Marti Gutierrez, Amy Koski, Rebecca Tippner-Hedges, Karen Agaronyan, Aida Platero-Luengo, Paloma Martinez-Redondo, Hong Ma, Yeonmi Lee and 20 more

RetractedErratum issuedAbstract read
PubMed Publisher
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. It has been retracted, and should not be counted. Cited by 169 papers.

0numbers the graph read from it
0cells of the map it votes in
169citing papers in PubMed
19.1field-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

169 citing papers in PubMed, 333 citations in OpenAlex.

  1. Trial
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  10. Mechanistic study on the role of multi-pathway autophagy in ovarian aging: literature review.Apoptosis : an international journal on programmed cell death · 2025
    Review
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  17. Causes of and Solutions to Mitochondrial Disorders: A Literature Review.International journal of molecular sciences · 2025
    Review
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  19. Review
  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

30 authors at 5 institutions in 1 country.

Eunju KangCenter for Embryonic Cell and Gene Therapy, Oregon Health &Science University, 3303 SW Bond Avenue, Portland, Oregon 97239, USA.
Jun WuGene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.
Nuria Marti GutierrezCenter for Embryonic Cell and Gene Therapy, Oregon Health &Science University, 3303 SW Bond Avenue, Portland, Oregon 97239, USA.
Amy KoskiCenter for Embryonic Cell and Gene Therapy, Oregon Health &Science University, 3303 SW Bond Avenue, Portland, Oregon 97239, USA.
Rebecca Tippner-HedgesCenter for Embryonic Cell and Gene Therapy, Oregon Health &Science University, 3303 SW Bond Avenue, Portland, Oregon 97239, USA.
Karen AgaronyanDepartment of Cell Biology School of Osteopathic Medicine, Rowan University, 2 Medical Center Drive, Stratford, New Jersey 08084, USA.
Aida Platero-LuengoGene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.
Paloma Martinez-RedondoGene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.
Hong MaCenter for Embryonic Cell and Gene Therapy, Oregon Health &Science University, 3303 SW Bond Avenue, Portland, Oregon 97239, USA.
Yeonmi LeeCenter for Embryonic Cell and Gene Therapy, Oregon Health &Science University, 3303 SW Bond Avenue, Portland, Oregon 97239, USA.
Tomonari HayamaCenter for Embryonic Cell and Gene Therapy, Oregon Health &Science University, 3303 SW Bond Avenue, Portland, Oregon 97239, USA.
Crystal Van DykenCenter for Embryonic Cell and Gene Therapy, Oregon Health &Science University, 3303 SW Bond Avenue, Portland, Oregon 97239, USA.
Xinjian WangDivision of Human Genetics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio 45229, USA.
Shiyu LuoDivision of Human Genetics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio 45229, USA.
Riffat AhmedCenter for Embryonic Cell and Gene Therapy, Oregon Health &Science University, 3303 SW Bond Avenue, Portland, Oregon 97239, USA.
Ying LiCenter for Embryonic Cell and Gene Therapy, Oregon Health &Science University, 3303 SW Bond Avenue, Portland, Oregon 97239, USA.
Dongmei JiCenter for Embryonic Cell and Gene Therapy, Oregon Health &Science University, 3303 SW Bond Avenue, Portland, Oregon 97239, USA.
Refik KayaliIviGen Los Angeles, 406 Amapola Avenue, Suite 215, Torrance, California 90501, USA.
Cengiz CinniogluIviGen Los Angeles, 406 Amapola Avenue, Suite 215, Torrance, California 90501, USA.
Susan OlsonResearch Cytogenetics Laboratory, Oregon Health &Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA.
Jeffrey JensenDivision of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Oregon Health &Science University, 3303 SW Bond Avenue, Portland, Oregon 97239, USA.
David BattagliaDivision of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Oregon Health &Science University, 3303 SW Bond Avenue, Portland, Oregon 97239, USA.
David LeeDivision of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Oregon Health &Science University, 3303 SW Bond Avenue, Portland, Oregon 97239, USA.
Diana WuDivision of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Oregon Health &Science University, 3303 SW Bond Avenue, Portland, Oregon 97239, USA.
Taosheng HuangDivision of Human Genetics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio 45229, USA.
Don P WolfCenter for Embryonic Cell and Gene Therapy, Oregon Health &Science University, 3303 SW Bond Avenue, Portland, Oregon 97239, USA.
Dmitry TemiakovDepartment of Cell Biology School of Osteopathic Medicine, Rowan University, 2 Medical Center Drive, Stratford, New Jersey 08084, USA.
Juan Carlos Izpisua BelmonteGene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.
Paula AmatoDivision of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Oregon Health &Science University, 3303 SW Bond Avenue, Portland, Oregon 97239, USA.
Shoukhrat MitalipovCenter for Embryonic Cell and Gene Therapy, Oregon Health &Science University, 3303 SW Bond Avenue, Portland, Oregon 97239, USA.
Oregon Health & Science University · USSalk Institute for Biological Studies · USCincinnati Children's Hospital Medical Center · USRowan University · USOregon National Primate Research Center · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Maternally inherited mitochondrial (mt)DNA mutations can cause fatal or severely debilitating syndromes in children, with disease severity dependent on the specific gene mutation and the ratio of mutant to wild-type mtDNA (heteroplasmy) in each cell and tissue. Pathogenic mtDNA mutations are relatively common, with an estimated 778 affected children born each year in the United States. Mitochondrial replacement therapies or techniques (MRT) circumventing mother-to-child mtDNA disease transmission involve replacement of oocyte maternal mtDNA. Here we report MRT outcomes in several families with common mtDNA syndromes. The mother's oocytes were of normal quality and mutation levels correlated with those in existing children. Efficient replacement of oocyte mutant mtDNA was performed by spindle transfer, resulting in embryos containing >99% donor mtDNA. Donor mtDNA was stably maintained in embryonic stem cells (ES cells) derived from most embryos. However, some ES cell lines demonstrated gradual loss of donor mtDNA and reversal to the maternal haplotype. In evaluating donor-to-maternal mtDNA interactions, it seems that compatibility relates to mtDNA replication efficiency rather than to mismatch or oxidative phosphorylation dysfunction. We identify a polymorphism within the conserved sequence box II region of the D-loop as a plausible cause of preferential replication of specific mtDNA haplotypes. In addition, some haplotypes confer proliferative and growth advantages to cells. Hence, we propose a matching paradigm for selecting compatible donor mtDNA for MRT.

Indexed as

MutationBlastocystCell LineConserved SequenceDNA, MitochondrialEmbryonic Stem CellsFemaleHaplotypesHumansMaleMaternal InheritanceMeiosisMitochondrial DiseasesMitochondrial Replacement TherapyOocyte DonationOocytesDNA, Mitochondrial

Identifiers

PMID27919073
OpenAlexW2558936320

What OpenQuestion holds

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Registered trials

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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.