Small Molecule-Triggered Cas9 Protein with Improved Genome-Editing Specificity

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-hydroxytam...

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Detalles Bibliográficos
Autores principales: Davis, Kevin M., Pattanayak, Vikram, Thompson, David B., Zuris, John A., Liu, David R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2015
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4402137/
https://www.ncbi.nlm.nih.gov/pubmed/25848930
http://dx.doi.org/10.1038/nchembio.1793
Descripción
Sumario: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 (4-HT)-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.

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