Aptazyme-embedded guide RNAs enable ligand-responsive genome editing and transcriptional activation

Nat Commun. 2017 Jun 28:8:15939. doi: 10.1038/ncomms15939.

Abstract

Programmable sequence-specific genome editing agents such as CRISPR-Cas9 have greatly advanced our ability to manipulate the human genome. Although canonical forms of genome-editing agents and programmable transcriptional regulators are constitutively active, precise temporal and spatial control over genome editing and transcriptional regulation activities would enable the more selective and potentially safer use of these powerful technologies. Here, by incorporating ligand-responsive self-cleaving catalytic RNAs (aptazymes) into guide RNAs, we developed a set of aptazyme-embedded guide RNAs that enable small molecule-controlled nuclease-mediated genome editing and small molecule-controlled base editing, as well as small molecule-dependent transcriptional activation in mammalian cells.

Publication types

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

MeSH terms

  • CRISPR-Cas Systems
  • Gene Editing*
  • HEK293 Cells
  • Humans
  • Ligands
  • Nucleic Acid Conformation
  • RNA, Catalytic / genetics
  • RNA, Catalytic / metabolism*
  • RNA, Guide, CRISPR-Cas Systems / chemistry
  • RNA, Guide, CRISPR-Cas Systems / genetics
  • RNA, Guide, CRISPR-Cas Systems / metabolism*
  • Transcriptional Activation*

Substances

  • Ligands
  • RNA, Catalytic
  • RNA, Guide, CRISPR-Cas Systems