A guide to genome engineering with programmable nucleases

Nat Rev Genet. 2014 May;15(5):321-34. doi: 10.1038/nrg3686. Epub 2014 Apr 2.


Programmable nucleases - including zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and RNA-guided engineered nucleases (RGENs) derived from the bacterial clustered regularly interspaced short palindromic repeat (CRISPR)-Cas (CRISPR-associated) system - enable targeted genetic modifications in cultured cells, as well as in whole animals and plants. The value of these enzymes in research, medicine and biotechnology arises from their ability to induce site-specific DNA cleavage in the genome, the repair (through endogenous mechanisms) of which allows high-precision genome editing. However, these nucleases differ in several respects, including their composition, targetable sites, specificities and mutation signatures, among other characteristics. Knowledge of nuclease-specific features, as well as of their pros and cons, is essential for researchers to choose the most appropriate tool for a range of applications.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • DNA Breaks, Double-Stranded
  • DNA Repair
  • Endonucleases / chemistry
  • Endonucleases / metabolism*
  • Genetic Engineering / methods*
  • Genome*
  • Humans
  • Mutagenesis, Site-Directed / methods*
  • Translocation, Genetic / genetics
  • Zinc Fingers


  • Endonucleases