Single-guide RNAs were designed with CRISPRtool (http://crispr.mit.edu) and then cloned into lentiCRISPR v2 (Addgene, 52961) vector. Targeting vector and single-stranded DNA donor were cotransfected in cells for 24 hours and followed by 2 days of puromycin selection. Targeted single-cell clones were screened by PCR.

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