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

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.

SUBMITTER: Davis KM 

PROVIDER: S-EPMC4402137 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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

Davis Kevin M KM   Pattanayak Vikram V   Thompson David B DB   Zuris John A JA   Liu David R DR  

Nature chemical biology 20150406 5

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. ...[more]

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