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
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author Davis, Kevin M.
Pattanayak, Vikram
Thompson, David B.
Zuris, John A.
Liu, David R.
author_facet Davis, Kevin M.
Pattanayak, Vikram
Thompson, David B.
Zuris, John A.
Liu, David R.
author_sort Davis, Kevin M.
collection PubMed
description 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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spelling pubmed-44021372015-11-01 Small Molecule-Triggered Cas9 Protein with Improved Genome-Editing Specificity Davis, Kevin M. Pattanayak, Vikram Thompson, David B. Zuris, John A. Liu, David R. Nat Chem Biol Article 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. 2015-04-06 2015-05 /pmc/articles/PMC4402137/ /pubmed/25848930 http://dx.doi.org/10.1038/nchembio.1793 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Davis, Kevin M.
Pattanayak, Vikram
Thompson, David B.
Zuris, John A.
Liu, David R.
Small Molecule-Triggered Cas9 Protein with Improved Genome-Editing Specificity
title Small Molecule-Triggered Cas9 Protein with Improved Genome-Editing Specificity
title_full Small Molecule-Triggered Cas9 Protein with Improved Genome-Editing Specificity
title_fullStr Small Molecule-Triggered Cas9 Protein with Improved Genome-Editing Specificity
title_full_unstemmed Small Molecule-Triggered Cas9 Protein with Improved Genome-Editing Specificity
title_short Small Molecule-Triggered Cas9 Protein with Improved Genome-Editing Specificity
title_sort small molecule-triggered cas9 protein with improved genome-editing specificity
topic Article
url 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
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