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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
Volume11
Issue5
Pages316-8
Date Published2015 May
ISSN1552-4469
KeywordsBacterial Proteins, Cells, Cultured, Endonucleases, Genome, HEK293 Cells, High-Throughput Nucleotide Sequencing, Humans, Ligands, Models, Molecular, Protein Conformation, Small Molecule Libraries, Tamoxifen
Abstract

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.

DOI10.1038/nchembio.1793
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/25848930?dopt=Abstract

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