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

Xiaojie Ma, Xi Chen, Yan Jin, Wenyan Ge, Weiyun Wang, Linghao Kong, Junfang Ji, Xing Guo, Jun Huang, Xin-Hua Feng, Junfen Fu and Saiyong Zhu ()
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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

Nature Communications, 2018, vol. 9, issue 1, 1-7

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-03760-5

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