Browse

Correction of a pathogenic gene mutation in human embryos

Cited 456 time in Web of Science Cited 489 time in Scopus
Authors
Ma, Hong; Marti-Gutierrez, Nuria; Park, Sang-Wook; Wu, Jun; Lee, Yeonmi; Suzuki, Keiichiro; Koski, Amy; Ji, Dongmei; Hayama, Tomonari; Ahmed, Riffat; Darby, Hayley; Van Dyken, Crystal; Li, Ying; Kang, Eunju; Park, A. -Reum; Kim, Daesik; Kim, Sang-Tae; Gong, Jianhui; Gu, Ying; Xu, Xun; Battaglia, David; Krieg, Sacha A.; Lee, David M.; Wu, Diana H.; Wolf, Don P.; Heitner, Stephen B.; Belmonte, Juan Carlos Izpisua; Mato, Paula A.; Kim, Jin-Soo; Kaul, Sanjiv; Mitalipov, Shoukhrat
Issue Date
2017-08
Citation
Nature, Vol.548 No.7668, pp.413-419
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.
ISSN
0028-0836
URI
https://hdl.handle.net/10371/165674
DOI
https://doi.org/10.1038/nature23305
Files in This Item:
There are no files associated with this item.
Appears in Collections:
Seoul National University(서울대학교)Featured Researcher's Articles
  • mendeley

Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse