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Reply to: Reversion after replacement of mitochondrial DNA

Nature volume 574, pages E12–E13 (2019)Cite this article

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The Original Article was published on 16 October 2019

replying to G. Hudson et al. Nature https://doi.org/10.1038/s41586-019-1623-3 (2019)

In the accompanying Comment1, Hudson et al. argue that one of our research volunteers (ED5, with U5a haplotype), who was assigned to the unaffected-oocyte cohort of donors in our original study2, should be allocated to the mitochondrial DNA (mtDNA)-disease group because she carries a homoplasmic m.14484T>C variant of mtDNA that is implicated in Leber’s hereditary optic neuropathy (LHON). However, for the purposes of our in vitro study, oocyte donors were assigned to the healthy cohort on the basis of clinical criteria alone—that is, the absence of a diagnosis or symptoms of disease caused by mutations in mtDNA. In addition, the inclusion and exclusion criteria of our approved study protocol dictated that, to be considered as possessing a pathogenic mutation in their mtDNA, the research volunteer had to be diagnosed with a maternally transmitted mitochondrial disease. Because this oocyte donor was healthy, and lacked any evidence of LHON in her family for four generations, she was assigned to the healthy-oocyte cohort of donors. However, carriers of 14484T>C variants of mtDNA should not be used as oocyte donors in future clinical applications of mitochondrial replacement therapy—whether the carrier is asymptomatic, or not.

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Fig. 1: Distribution of reversed ES cell lines based on CSBII sequence.

Data availability

All data presented in this study have previously been published2,3,4.

References

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Author information

Authors and Affiliations

  1. Department of Convergence Medicine and Stem Cell Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea

    Eunju Kang

  2. Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, Portland, OR, USA

    Amy Koski, Paula Amato & Shoukhrat Mitalipov

  3. Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Oregon Health & Science University, Portland, OR, USA

    Paula Amato & Shoukhrat Mitalipov

  4. Department of Biochemistry and Molecular Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA

    Dmitry Temiakov

Authors
  1. Eunju Kang
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  2. Amy Koski
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  3. Paula Amato
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  4. Dmitry Temiakov
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  5. Shoukhrat Mitalipov
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Contributions

E.K., A. K. and S.M. drafted the first version of the manuscript. E.K., A. K., P.A., D.T., and S.M. provided feedback and edited the final version.

Corresponding author

Correspondence to Shoukhrat Mitalipov.

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Competing interests

S.M. is a co-founder and shareholder of Mitogenome Therapeutics, Inc. The other authors declare no competing financial interests

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Kang, E., Koski, A., Amato, P. et al. Reply to: Reversion after replacement of mitochondrial DNA. Nature 574, E12–E13 (2019). https://doi.org/10.1038/s41586-019-1624-2

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