Human cleaving embryos enable robust homozygotic nucleotide substitutions by base editors

Meiling Zhang, Changyang Zhou, Yu Wei, Chunlong Xu, Hong Pan, Wenqin Ying, Yidi Sun, Yun Sun, Qingquan Xiao, Ning Yao, Wanxia Zhong, Yun Li, Keliang Wu, Gao Yuan, Shoukhrat Mitalipov, Zi Jiang Chen, Hui Yang

    Research output: Contribution to journalArticle

    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 languageEnglish (US)
    Article number101
    JournalGenome biology
    Volume20
    Issue number1
    DOIs
    StatePublished - May 22 2019

    Fingerprint

    embryo
    embryo (animal)
    substitution
    Embryonic Structures
    Nucleotides
    nucleotides
    gene
    Zygote
    gene targeting
    zygote
    point mutation
    Point Mutation
    Genes
    Oocytes
    mutation
    oocytes
    cells
    fold
    loci
    genes

    Keywords

    • Base editing
    • Homozygotic nucleotide substitution
    • Human cleaving embryos

    ASJC Scopus subject areas

    • Ecology, Evolution, Behavior and Systematics
    • Genetics
    • Cell Biology

    Cite this

    Zhang, M., Zhou, C., Wei, Y., Xu, C., Pan, H., Ying, W., ... Yang, H. (2019). Human cleaving embryos enable robust homozygotic nucleotide substitutions by base editors. Genome biology, 20(1), [101]. https://doi.org/10.1186/s13059-019-1703-6

    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 journalArticle

    Zhang, M, Zhou, C, Wei, Y, Xu, C, Pan, H, Ying, W, Sun, Y, Sun, Y, Xiao, Q, Yao, N, Zhong, W, Li, Y, Wu, K, Yuan, G, Mitalipov, S, Chen, ZJ & Yang, H 2019, 'Human cleaving embryos enable robust homozygotic nucleotide substitutions by base editors', Genome biology, vol. 20, no. 1, 101. https://doi.org/10.1186/s13059-019-1703-6
    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. / Human cleaving embryos enable robust homozygotic nucleotide substitutions by base editors. In: Genome biology. 2019 ; Vol. 20, No. 1.
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