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Nat Chem Biol DOI:10.1038/nchembio.1793

Small molecule-triggered Cas9 protein with improved genome-editing specificity.

Publication TypeJournal Article
Year of Publication2015
AuthorsDavis, KM, Pattanayak, V, Thompson, DB, Zuris, JA, Liu, DR
JournalNat Chem Biol
Date Published2015 May
KeywordsBacterial Proteins, Cells, Cultured, Endonucleases, Genome, HEK293 Cells, High-Throughput Nucleotide Sequencing, Humans, Ligands, Models, Molecular, Protein Conformation, Small Molecule Libraries, Tamoxifen

Directly modulating the activity of genome-editing proteins has the potential to increase their specificity by reducing activity following target locus modification. We developed Cas9 nucleases that are activated by the presence of a cell-permeable small molecule by inserting an evolved 4-hydroxytamoxifen-responsive intein at specific positions in Cas9. In human cells, conditionally active Cas9s modify target genomic sites with up to 25-fold higher specificity than wild-type Cas9.


Alternate JournalNat. Chem. Biol.
PubMed ID25848930
PubMed Central IDPMC4402137
Grant ListF32 GM 106601-2 / GM / NIGMS NIH HHS / United States
T32 GM007753 / GM / NIGMS NIH HHS / United States
/ / Howard Hughes Medical Institute / United States
F32 GM106601 / GM / NIGMS NIH HHS / United States
R01 GM095501 / GM / NIGMS NIH HHS / United States