Controlling and enhancing CRISPR systems

Nat Chem Biol. 2021 Jan;17(1):10-19. doi: 10.1038/s41589-020-00700-7. Epub 2020 Dec 16.


Many bacterial and archaeal organisms use clustered regularly interspaced short palindromic repeats-CRISPR associated (CRISPR-Cas) systems to defend themselves from mobile genetic elements. These CRISPR-Cas systems are classified into six types based on their composition and mechanism. CRISPR-Cas enzymes are widely used for genome editing and offer immense therapeutic opportunity to treat genetic diseases. To realize their full potential, it is important to control the timing, duration, efficiency and specificity of CRISPR-Cas enzyme activities. In this Review we discuss the mechanisms of natural CRISPR-Cas regulatory biomolecules and engineering strategies that enhance or inhibit CRISPR-Cas immunity by altering enzyme function. We also discuss the potential applications of these CRISPR regulators and highlight unanswered questions about their evolution and purpose in nature.

Publication types

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

MeSH terms

  • Antibiosis / genetics
  • Archaea / genetics*
  • Archaea / metabolism
  • Archaea / virology
  • Bacteria / genetics*
  • Bacteria / metabolism
  • Bacteria / virology
  • Bacteriophages / genetics
  • Bacteriophages / growth & development
  • Bacteriophages / metabolism
  • CRISPR-Associated Protein 9 / genetics
  • CRISPR-Associated Protein 9 / metabolism
  • CRISPR-Cas Systems*
  • Clustered Regularly Interspaced Short Palindromic Repeats*
  • Gene Editing / methods
  • Gene Expression Regulation, Archaeal*
  • Gene Expression Regulation, Bacterial*
  • Genetic Engineering / methods
  • Humans
  • Interspersed Repetitive Sequences
  • RNA, Guide, CRISPR-Cas Systems / genetics
  • RNA, Guide, CRISPR-Cas Systems / metabolism


  • RNA, Guide, CRISPR-Cas Systems
  • CRISPR-Associated Protein 9