Enhancing zinc-finger-nuclease activity with improved obligate heterodimeric architectures View Full Text


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Article Info

DATE

2011-01

AUTHORS

Yannick Doyon, Thuy D Vo, Matthew C Mendel, Shon G Greenberg, Jianbin Wang, Danny F Xia, Jeffrey C Miller, Fyodor D Urnov, Philip D Gregory, Michael C Holmes

ABSTRACT

Zinc-finger nucleases (ZFNs) drive efficient genome editing by introducing a double-strand break into the targeted gene. Cleavage is induced when two custom-designed ZFNs heterodimerize upon binding DNA to form a catalytically active nuclease complex. The importance of this dimerization event for subsequent cleavage activity has stimulated efforts to engineer the nuclease interface to prevent undesired homodimerization. Here we report the development and application of a yeast-based selection system designed to functionally interrogate the ZFN dimer interface. We identified critical residues involved in dimerization through the isolation of cold-sensitive nuclease domains. We used these residues to engineer ZFNs that have superior cleavage activity while suppressing homodimerization. The improvements were portable to orthogonal domains, allowing the concomitant and independent cleavage of two loci using two different ZFN pairs. These ZFN architectures provide a general means for obtaining highly efficient and specific genome modification. More... »

PAGES

74

References to SciGraph publications

  • 2009-05. Precise genome modification in the crop species Zea mays using zinc-finger nucleases in NATURE
  • 2005-06. Highly efficient endogenous human gene correction using designed zinc-finger nucleases in NATURE
  • 2010-01. Engineering a polarity-sensitive biosensor for time-lapse imaging of apoptotic processes and degeneration in NATURE METHODS
  • 2008-06. Heritable targeted gene disruption in zebrafish using designed zinc-finger nucleases in NATURE BIOTECHNOLOGY
  • 2010-06. Transient cold shock enhances zinc-finger nuclease–mediated gene disruption in NATURE METHODS
  • 2008-07. Establishment of HIV-1 resistance in CD4+ T cells by genome editing using zinc-finger nucleases in NATURE BIOTECHNOLOGY
  • 2010-09. Genome editing with engineered zinc finger nucleases in NATURE REVIEWS GENETICS
  • 2010-08. Human hematopoietic stem/progenitor cells modified by zinc-finger nucleases targeted to CCR5 control HIV-1 in vivo in NATURE BIOTECHNOLOGY
  • 2009-04. Targeted transgene integration in plant cells using designed zinc finger nucleases in PLANT MOLECULAR BIOLOGY
  • 2007-07. Structure-based redesign of the dimerization interface reduces the toxicity of zinc-finger nucleases in NATURE BIOTECHNOLOGY
  • 2010-02. Genome editing with modularly assembled zinc-finger nucleases in NATURE METHODS
  • 2007-07. An improved zinc-finger nuclease architecture for highly specific genome editing in NATURE BIOTECHNOLOGY
  • 2008-11. Progress and prospects: Zinc-finger nucleases as gene therapy agents in GENE THERAPY
  • 2010-06-25. A Rapid and General Assay for Monitoring Endogenous Gene Modification in ENGINEERED ZINC FINGER PROTEINS
  • Journal

    TITLE

    Nature Methods

    ISSUE

    1

    VOLUME

    8

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nmeth.1539

    DOI

    http://dx.doi.org/10.1038/nmeth.1539

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1010147854

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/21131970


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