Controlling CRISPR-Cas9 with ligand-activated and ligand-deactivated sgRNAs

Nat Commun. 2019 May 9;10(1):2127. doi: 10.1038/s41467-019-09985-2.


The CRISPR-Cas9 system provides the ability to edit, repress, activate, or mark any gene (or DNA element) by pairing of a programmable single guide RNA (sgRNA) with a complementary sequence on the DNA target. Here we present a new method for small-molecule control of CRISPR-Cas9 function through insertion of RNA aptamers into the sgRNA. We show that CRISPR-Cas9-based gene repression (CRISPRi) can be either activated or deactivated in a dose-dependent fashion over a >10-fold dynamic range in response to two different small-molecule ligands. Since our system acts directly on each target-specific sgRNA, it enables new applications that require differential and opposing temporal control of multiple genes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aptamers, Nucleotide / genetics*
  • CRISPR-Associated Protein 9 / genetics*
  • CRISPR-Cas Systems / genetics*
  • DNA / genetics
  • Gene Editing / methods*
  • Ligands
  • RNA, Guide / genetics*


  • Aptamers, Nucleotide
  • Ligands
  • RNA, Guide
  • DNA
  • CRISPR-Associated Protein 9