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Small molecules promote CRISPR-Cpf1-mediated genome editing in human pluripotent stem cells

Author

Listed:
  • Xiaojie Ma

    (Zhejiang University)

  • Xi Chen

    (Zhejiang University)

  • Yan Jin

    (Zhejiang University)

  • Wenyan Ge

    (Zhejiang University)

  • Weiyun Wang

    (Zhejiang University)

  • Linghao Kong

    (Zhejiang University)

  • Junfang Ji

    (Zhejiang University)

  • Xing Guo

    (Zhejiang University)

  • Jun Huang

    (Zhejiang University)

  • Xin-Hua Feng

    (Zhejiang University)

  • Junfen Fu

    (Zhejiang University School of Medicine)

  • Saiyong Zhu

    (Zhejiang University
    Zhejiang University)

Abstract

Human pluripotent stem cells (hPSCs) have potential applications in biological studies and regenerative medicine. However, precise genome editing in hPSCs remains time-consuming and labor-intensive. Here we demonstrate that the recently identified CRISPR-Cpf1 can be used to efficiently generate knockout and knockin hPSC lines. The unique properties of CRISPR-Cpf1, including shorter crRNA length and low off-target activity, are very attractive for many applications. In particular, we develop an unbiased drug-selection-based platform feasible for high-throughput screening in hPSCs and this screening system enables us to identify small molecules VE-822 and AZD-7762 that can promote CRISPR-Cpf1-mediated precise genome editing. Significantly, the combination of CRISPR-Cpf1 and small molecules provides a simple and efficient strategy for precise genome engineering.

Suggested Citation

  • Xiaojie Ma & Xi Chen & Yan Jin & Wenyan Ge & Weiyun Wang & Linghao Kong & Junfang Ji & Xing Guo & Jun Huang & Xin-Hua Feng & Junfen Fu & Saiyong Zhu, 2018. "Small molecules promote CRISPR-Cpf1-mediated genome editing in human pluripotent stem cells," Nature Communications, Nature, vol. 9(1), pages 1-7, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03760-5
    DOI: 10.1038/s41467-018-03760-5
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    Cited by:

    1. Xiaojie Ma & Jie Cao & Ziyu Zhou & Yunkun Lu & Qin Li & Yan Jin & Guo Chen & Weiyun Wang & Wenyan Ge & Xi Chen & Zhensheng Hu & Xiao Shu & Qian Deng & Jiaqi Pu & Chengzhen Liang & Junfen Fu & Jianzhao, 2022. "N6-methyladenosine modification-mediated mRNA metabolism is essential for human pancreatic lineage specification and islet organogenesis," Nature Communications, Nature, vol. 13(1), pages 1-14, December.

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