Nuclear genome transfer in human oocytes eliminates mitochondrial DNA variants

Daniel Paull, Valentina Emmanuele, Keren A. Weiss, Nathan Treff, Latoya Stewart, Haiqing Hua, Matthew Zimmer, David J. Kahler, Robin S. Goland, Scott A. Noggle, Robert Prosser, Michio Hirano, Mark V. Sauer () and Dieter Egli ()
Additional contact information
Daniel Paull: The New York Stem Cell Foundation Laboratory
Valentina Emmanuele: Columbia University
Keren A. Weiss: The New York Stem Cell Foundation Laboratory
Nathan Treff: Reproductive Medicine Associates of New Jersey
Latoya Stewart: The New York Stem Cell Foundation Laboratory
Haiqing Hua: The New York Stem Cell Foundation Laboratory
Matthew Zimmer: The New York Stem Cell Foundation Laboratory
David J. Kahler: The New York Stem Cell Foundation Laboratory
Robin S. Goland: Naomi Berrie Diabetes Center, College of Physicians and Surgeons, Columbia University
Scott A. Noggle: The New York Stem Cell Foundation Laboratory
Robert Prosser: Center for Women’s Reproductive Care, College of Physicians and Surgeons, Columbia University
Michio Hirano: Columbia University
Mark V. Sauer: Center for Women’s Reproductive Care, College of Physicians and Surgeons, Columbia University
Dieter Egli: The New York Stem Cell Foundation Laboratory

Nature, 2013, vol. 493, issue 7434, 632-637

Abstract: Abstract Mitochondrial DNA mutations transmitted maternally within the oocyte cytoplasm often cause life-threatening disorders. Here we explore the use of nuclear genome transfer between unfertilized oocytes of two donors to prevent the transmission of mitochondrial mutations. Nuclear genome transfer did not reduce developmental efficiency to the blastocyst stage, and genome integrity was maintained provided that spontaneous oocyte activation was avoided through the transfer of incompletely assembled spindle–chromosome complexes. Mitochondrial DNA transferred with the nuclear genome was initially detected at levels below 1%, decreasing in blastocysts and stem-cell lines to undetectable levels, and remained undetectable after passaging for more than one year, clonal expansion, differentiation into neurons, cardiomyocytes or β-cells, and after cellular reprogramming. Stem cells and differentiated cells had mitochondrial respiratory chain enzyme activities and oxygen consumption rates indistinguishable from controls. These results demonstrate the potential of nuclear genome transfer to prevent the transmission of mitochondrial disorders in humans.

Date: 2013
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/nature11800 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:493:y:2013:i:7434:d:10.1038_nature11800

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature11800

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().