A chemical-inducible CRISPR–Cas9 system for rapid control of genome editing View Full Text


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Article Info

DATE

2016-11

AUTHORS

Kaiwen Ivy Liu, Muhammad Nadzim Bin Ramli, Cheok Wei Ariel Woo, Yuanming Wang, Tianyun Zhao, Xiujun Zhang, Guo Rong Daniel Yim, Bao Yi Chong, Ali Gowher, Mervyn Zi Hao Chua, Jonathan Jung, Jia Hui Jane Lee, Meng How Tan

ABSTRACT

CRISPR-Cas9 has emerged as a powerful technology that enables ready modification of the mammalian genome. The ability to modulate Cas9 activity can reduce off-target cleavage and facilitate precise genome engineering. Here we report the development of a Cas9 variant whose activity can be switched on and off in human cells with 4-hydroxytamoxifen (4-HT) by fusing the Cas9 enzyme with the hormone-binding domain of the estrogen receptor (ERT2). The final optimized variant, termed iCas, showed low endonuclease activity without 4-HT but high editing efficiency at multiple loci with the chemical. We also tuned the duration and concentration of 4-HT treatment to reduce off-target genome modification. Additionally, we benchmarked iCas against other chemical-inducible methods and found that it had the fastest on rate and that its activity could be toggled on and off repeatedly. Collectively, these results highlight the utility of iCas for rapid and reversible control of genome-editing function. More... »

PAGES

980-987

References to SciGraph publications

  • 2013-09. CAS9 transcriptional activators for target specificity screening and paired nickases for cooperative genome engineering in NATURE BIOTECHNOLOGY
  • 2013-09. High-frequency off-target mutagenesis induced by CRISPR-Cas nucleases in human cells in NATURE BIOTECHNOLOGY
  • 2010-12. REAP: A two minute cell fractionation method in BMC RESEARCH NOTES
  • 2014-06. Fusion of catalytically inactive Cas9 to FokI nuclease improves the specificity of genome modification in NATURE BIOTECHNOLOGY
  • 2016-01. High-fidelity CRISPR–Cas9 nucleases with no detectable genome-wide off-target effects in NATURE
  • 2015-03. Unbiased detection of off-target cleavage by CRISPR-Cas9 and TALENs using integrase-defective lentiviral vectors in NATURE BIOTECHNOLOGY
  • 2015-07. Photoactivatable CRISPR-Cas9 for optogenetic genome editing in NATURE BIOTECHNOLOGY
  • 2015-03. GUIDE-seq enables genome-wide profiling of off-target cleavage by CRISPR-Cas nucleases in NATURE BIOTECHNOLOGY
  • 2015-04. Inducible in vivo genome editing with CRISPR-Cas9 in NATURE BIOTECHNOLOGY
  • 2015-03. A split-Cas9 architecture for inducible genome editing and transcription modulation in NATURE BIOTECHNOLOGY
  • 2014-03. Improving CRISPR-Cas nuclease specificity using truncated guide RNAs in NATURE BIOTECHNOLOGY
  • 2015-01. Cationic lipid-mediated delivery of proteins enables efficient protein-based genome editing in vitro and in vivo in NATURE BIOTECHNOLOGY
  • 2015-05. Small molecule–triggered Cas9 protein with improved genome-editing specificity in NATURE CHEMICAL BIOLOGY
  • 2009-12. A recombinant polypeptide extends the in vivo half-life of peptides and proteins in a tunable manner in NATURE BIOTECHNOLOGY
  • 2014-04. Efficient genome modification by CRISPR-Cas9 nickase with minimal off-target effects in NATURE METHODS
  • 2015-03. A light-inducible CRISPR-Cas9 system for control of endogenous gene activation in NATURE CHEMICAL BIOLOGY
  • 2014-06. Dimeric CRISPR RNA-guided FokI nucleases for highly specific genome editing in NATURE BIOTECHNOLOGY
  • 2013-03. Targeted genome engineering in human cells with the Cas9 RNA-guided endonuclease in NATURE BIOTECHNOLOGY
  • 2013-08. Optical control of mammalian endogenous transcription and epigenetic states in NATURE
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nchembio.2179

    DOI

    http://dx.doi.org/10.1038/nchembio.2179

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1037967734

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/27618190


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    Download the RDF metadata as:  json-ld nt turtle xml License info

    HOW TO GET THIS DATA PROGRAMMATICALLY:

    JSON-LD is a popular format for linked data which is fully compatible with JSON.

    curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/nchembio.2179'

    N-Triples is a line-based linked data format ideal for batch operations.

    curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/nchembio.2179'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/nchembio.2179'

    RDF/XML is a standard XML format for linked data.

    curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/nchembio.2179'


     

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