Jinek, M., et al. Science 337, 816–821 (2012).

To fend off intruding viruses and plasmids, bacteria use CRISPR (clusters of regularly interspaced short palindromic repeat) RNAs to guide foreign nucleic acids to a silencing effector complex. Jinek et al. show that in the case of CRISPR effector Cas9, two distinct small RNAs direct the complex to specifically bind and cleave DNA. The authors recognized that the blunt-ended cut created by Cas9 could in principle be used to selectively edit any genome, much as with other gene-targeting nucleases. Yet the system does not require protein engineering, instead needing only Cas9 and one hybrid RNA molecule containing a targeting sequence, making it easy to generate unique RNA-guided nucleases for nearly any locus. They demonstrated the method by producing lesions in vitro in plasmid-encoded GFP.