Correction of a pathogenic gene mutation in human embryos Highly Cited Paper

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Title
Correction of a pathogenic gene mutation in human embryos
Author(s)
Hong Ma; Nuria Marti-Gutierrez; Sang-Wook Park; Jun Wu; Yeonmi Lee; Keiichiro Suzuki; Amy Koski; Dongmei Ji; Tomonari Hayama; Riffat Ahmed; Hayley Darby; Crystal Van Dyken; Ying Li; Eunju Kang; A.-Reum Park; Daesik Kim; Sang-Tae Kim; Jianhui Gong; Ying Gu; Xun Xu; David Battaglia; Sacha A. Krieg; David M. Lee; Diana H. Wu; Don P. Wolf; Stephen B. Heitner; Juan Carlos Izpisua Belmonte; Paula Amato; Jin-Soo Kim; Sanjiv Kaul; Shoukhrat Mitalipov
Publication Date
2017-08
Journal
NATURE, v.548, no.7668, pp.413 - 419
Publisher
NATURE PUBLISHING GROUP
Abstract
Genome editing has potential for the targeted correction of germline mutations. Here we describe the correction of the heterozygous MYBPC3 mutation in human preimplantation embryos with precise CRISPR-Cas9-based targeting accuracy and high homology-directed repair efficiency by activating an endogenous, germline-specific DNA repair response. Induced double-strand breaks (DSBs) at the mutant paternal allele were predominantly repaired using the homologous wild-type maternal gene instead of a synthetic DNA template. By modulating the cell cycle stage at which the DSB was induced, we were able to avoid mosaicism in cleaving embryos and achieve a high yield of homozygous embryos carrying the wild-type MYBPC3 gene without evidence of off-target mutations. The efficiency, accuracy and safety of the approach presented suggest that it has potential to be used for the correction of heritable mutations in human embryos by complementing preimplantation genetic diagnosis. However, much remains to be considered before clinical applications, including the reproducibility of the technique with other heterozygous mutations. © 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved
URI
https://pr.ibs.re.kr/handle/8788114/4016
ISSN
0028-0836
Appears in Collections:
Center for Genome Engineering(유전체 교정 연구단) > Journal Papers (저널논문)
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