CRISPR/Cas9: a historical and chemical biology perspective of targeted genome engineering

Chem Soc Rev. 2016 Dec 21;45(24):6666-6684. doi: 10.1039/c6cs00197a. Epub 2016 Sep 14.


The CRISPR-Cas9 system has revolutionized the process of making changes to the DNA sequence of organisms. Relying on a simplistic model of RNA guided DNA binding and cleavage, this molecular toolbox has found application in nearly every branch of biological sciences. The story of CRISPR-Cas9 is one of discovery and development where a component of bacterial adaptive immunity has been harnessed to address important biological questions using significant inputs from physicochemical structure-function studies. In this review, we trace the evolution of CRISPR-Cas9 from its predecessor genome editing tools and document its current status with an emphasis on chemical biology aspects of modulating its activity to generate a potent tool for gene therapy applications.

Publication types

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

MeSH terms

  • CRISPR-Cas Systems*
  • DNA / genetics
  • DNA Cleavage
  • Gene Editing / methods
  • Genetic Engineering / methods*
  • Genetic Therapy / methods
  • Humans
  • Protein Binding
  • Protein Conformation
  • Recombinases / genetics
  • Recombination, Genetic
  • Transcription Activator-Like Effector Nucleases / genetics
  • Zinc Finger Nucleases / genetics


  • Recombinases
  • DNA
  • Transcription Activator-Like Effector Nucleases
  • Zinc Finger Nucleases