Dimeric CRISPR RNA-guided FokI nucleases for highly specific genome editing View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-06

AUTHORS

Shengdar Q Tsai, Nicolas Wyvekens, Cyd Khayter, Jennifer A Foden, Vishal Thapar, Deepak Reyon, Mathew J Goodwin, Martin J Aryee, J Keith Joung

ABSTRACT

Monomeric CRISPR-Cas9 nucleases are widely used for targeted genome editing but can induce unwanted off-target mutations with high frequencies. Here we describe dimeric RNA-guided FokI nucleases (RFNs) that can recognize extended sequences and edit endogenous genes with high efficiencies in human cells. RFN cleavage activity depends strictly on the binding of two guide RNAs (gRNAs) to DNA with a defined spacing and orientation substantially reducing the likelihood that a suitable target site will occur more than once in the genome and therefore improving specificities relative to wild-type Cas9 monomers. RFNs guided by a single gRNA generally induce lower levels of unwanted mutations than matched monomeric Cas9 nickases. In addition, we describe a simple method for expressing multiple gRNAs bearing any 5' end nucleotide, which gives dimeric RFNs a broad targeting range. RFNs combine the ease of RNA-based targeting with the specificity enhancement inherent to dimerization and are likely to be useful in applications that require highly precise genome editing. More... »

PAGES

569

References to SciGraph publications

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  • Journal

    TITLE

    Nature Biotechnology

    ISSUE

    6

    VOLUME

    32

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nbt.2908

    DOI

    http://dx.doi.org/10.1038/nbt.2908

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1012868720

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/24770325


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