Abstract
Base editing installs a precise nucleotide change in specific gene loci without causing a double-strand break. Its efficiency in human embryos is generally low, limiting its utility in functional genetic studies. Here, we report that injecting base editors into human cleaving two-cell and four-cell embryos results in much higher (up to 13-fold) homozygotic nucleotide substitution efficiency as opposed to MII oocytes or zygotes. Furthermore, as a proof-of-principle study, a point mutation can be efficiently corrected by our method. Our study indicates that human cleaving embryos provide an efficient base editing window for robust gene disruption and correction.
| Original language | English (US) |
|---|---|
| Article number | 101 |
| Journal | Genome biology |
| Volume | 20 |
| Issue number | 1 |
| DOIs | |
| State | Published - May 22 2019 |
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Keywords
- Base editing
- Homozygotic nucleotide substitution
- Human cleaving embryos
ASJC Scopus subject areas
- Ecology, Evolution, Behavior and Systematics
- Genetics
- Cell Biology
Cite this
Human cleaving embryos enable robust homozygotic nucleotide substitutions by base editors. / Zhang, Meiling; Zhou, Changyang; Wei, Yu; Xu, Chunlong; Pan, Hong; Ying, Wenqin; Sun, Yidi; Sun, Yun; Xiao, Qingquan; Yao, Ning; Zhong, Wanxia; Li, Yun; Wu, Keliang; Yuan, Gao; Mitalipov, Shoukhrat; Chen, Zi Jiang; Yang, Hui.
In: Genome biology, Vol. 20, No. 1, 101, 22.05.2019.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Human cleaving embryos enable robust homozygotic nucleotide substitutions by base editors
AU - Zhang, Meiling
AU - Zhou, Changyang
AU - Wei, Yu
AU - Xu, Chunlong
AU - Pan, Hong
AU - Ying, Wenqin
AU - Sun, Yidi
AU - Sun, Yun
AU - Xiao, Qingquan
AU - Yao, Ning
AU - Zhong, Wanxia
AU - Li, Yun
AU - Wu, Keliang
AU - Yuan, Gao
AU - Mitalipov, Shoukhrat
AU - Chen, Zi Jiang
AU - Yang, Hui
PY - 2019/5/22
Y1 - 2019/5/22
N2 - Base editing installs a precise nucleotide change in specific gene loci without causing a double-strand break. Its efficiency in human embryos is generally low, limiting its utility in functional genetic studies. Here, we report that injecting base editors into human cleaving two-cell and four-cell embryos results in much higher (up to 13-fold) homozygotic nucleotide substitution efficiency as opposed to MII oocytes or zygotes. Furthermore, as a proof-of-principle study, a point mutation can be efficiently corrected by our method. Our study indicates that human cleaving embryos provide an efficient base editing window for robust gene disruption and correction.
AB - Base editing installs a precise nucleotide change in specific gene loci without causing a double-strand break. Its efficiency in human embryos is generally low, limiting its utility in functional genetic studies. Here, we report that injecting base editors into human cleaving two-cell and four-cell embryos results in much higher (up to 13-fold) homozygotic nucleotide substitution efficiency as opposed to MII oocytes or zygotes. Furthermore, as a proof-of-principle study, a point mutation can be efficiently corrected by our method. Our study indicates that human cleaving embryos provide an efficient base editing window for robust gene disruption and correction.
KW - Base editing
KW - Homozygotic nucleotide substitution
KW - Human cleaving embryos
UR - http://www.scopus.com/inward/record.url?scp=85066466267&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85066466267&partnerID=8YFLogxK
U2 - 10.1186/s13059-019-1703-6
DO - 10.1186/s13059-019-1703-6
M3 - Article
C2 - 31118069
AN - SCOPUS:85066466267
VL - 20
JO - Genome Biology
JF - Genome Biology
SN - 1474-7596
IS - 1
M1 - 101
ER -