Small Molecule-Triggered Cas9 Protein with Improved Genome-Editing Specificity
By K. Davis, V. Pattanayak, David B. Thompson, John A. Zuris, David R. Liu. 2015
392 citations recorded by the source corpus.
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.
Subfields: Cardiology and Cardiovascular Medicine, Molecular Biology
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Citations in the corpus
- Biology and Applications of CRISPR Systems: Harnessing Nature's Toolbox for Genome Engineering. (2016, neutral): “Recent work has focused on developing various chemical- and light-inducible Cas9 constructs to allow for greater spatiotemporal control and on employing Cas9 orthologs with different PAM sequences and smaller sizes, allowing for easier packaging in adeno-associated virus vectors (Davis et al., 2015;”
- CRISPR/Cas9 in Genome Editing and Beyond. (2016, positive): “(158) created intein-Cas9 fusion proteins that produce active Cas9s when a cell-permeable ligand is present.”