Cell Stem Cell 2015-02-05

Small molecules enhance CRISPR genome editing in pluripotent stem cells.

Chen Yu, Yanxia Liu, Tianhua Ma, Kai Liu, Shaohua Xu, Yu Zhang, Honglei Liu, Marie La Russa, Min Xie, Sheng Ding, Lei S Qi

文献索引：Cell Stem Cell 16(2) , 142-7, (2015)

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摘要

The bacterial CRISPR-Cas9 system has emerged as an effective tool for sequence-specific gene knockout through non-homologous end joining (NHEJ), but it remains inefficient for precise editing of genome sequences. Here we develop a reporter-based screening approach for high-throughput identification of chemical compounds that can modulate precise genome editing through homology-directed repair (HDR). Using our screening method, we have identified small molecules that can enhance CRISPR-mediated HDR efficiency, 3-fold for large fragment insertions and 9-fold for point mutations. Interestingly, we have also observed that a small molecule that inhibits HDR can enhance frame shift insertion and deletion (indel) mutations mediated by NHEJ. The identified small molecules function robustly in diverse cell types with minimal toxicity. The use of small molecules provides a simple and effective strategy to enhance precise genome engineering applications and facilitates the study of DNA repair mechanisms in mammalian cells.Copyright © 2015 Elsevier Inc. All rights reserved.

相关化合物

  • 齐多夫定
  • 布雷菲德菌素A
  • L755507

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