Improving the DNA specificity and applicability of base editing through protein engineering and protein delivery View Full Text


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Article Info

DATE

2017-06-06

AUTHORS

Holly A. Rees, Alexis C. Komor, Wei-Hsi Yeh, Joana Caetano-Lopes, Matthew Warman, Albert S. B. Edge, David R. Liu

ABSTRACT

We recently developed base editing, a genome-editing approach that enables the programmable conversion of one base pair into another without double-stranded DNA cleavage, excess stochastic insertions and deletions, or dependence on homology-directed repair. The application of base editing is limited by off-target activity and reliance on intracellular DNA delivery. Here we describe two advances that address these limitations. First, we greatly reduce off-target base editing by installing mutations into our third-generation base editor (BE3) to generate a high-fidelity base editor (HF-BE3). Next, we purify and deliver BE3 and HF-BE3 as ribonucleoprotein (RNP) complexes into mammalian cells, establishing DNA-free base editing. RNP delivery of BE3 confers higher specificity even than plasmid transfection of HF-BE3, while maintaining comparable on-target editing levels. Finally, we apply these advances to deliver BE3 RNPs into both zebrafish embryos and the inner ear of live mice to achieve specific, DNA-free base editing in vivo. More... »

PAGES

15790

References to SciGraph publications

  • 2014-06. Genome editing with Cas9 in adult mice corrects a disease mutation and phenotype in NATURE BIOTECHNOLOGY
  • 2016-12. Targeted AID-mediated mutagenesis (TAM) enables efficient genomic diversification in mammalian cells in NATURE METHODS
  • 2017-02-27. Highly efficient RNA-guided base editing in mouse embryos in NATURE BIOTECHNOLOGY
  • 2016-05. Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage in NATURE
  • 2013-09. High-throughput profiling of off-target DNA cleavage reveals RNA-programmed Cas9 nuclease specificity in NATURE BIOTECHNOLOGY
  • 2014-12. Genome dynamics of the human embryonic kidney 293 lineage in response to cell biology manipulations in NATURE COMMUNICATIONS
  • 2013-11. Genome engineering using the CRISPR-Cas9 system in NATURE PROTOCOLS
  • 2016-01. High-fidelity CRISPR–Cas9 nucleases with no detectable genome-wide off-target effects in NATURE
  • 2013-09. High-frequency off-target mutagenesis induced by CRISPR-Cas nucleases in human cells in NATURE BIOTECHNOLOGY
  • 2016-12. Directed evolution using dCas9-targeted somatic hypermutation in mammalian cells in NATURE METHODS
  • 2015-03. GUIDE-seq enables genome-wide profiling of off-target cleavage by CRISPR-Cas nucleases in NATURE BIOTECHNOLOGY
  • 2001-01. Viral vectors for gene therapy: the art of turning infectious agents into vehicles of therapeutics in NATURE MEDICINE
  • 2014-04. CRISPR-Cas systems for editing, regulating and targeting genomes in NATURE BIOTECHNOLOGY
  • 2016-02. Optimized sgRNA design to maximize activity and minimize off-target effects of CRISPR-Cas9 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
  • 2013-09. DNA targeting specificity of RNA-guided Cas9 nucleases in NATURE BIOTECHNOLOGY
  • 2015-05. Small molecule–triggered Cas9 protein with improved genome-editing specificity in NATURE CHEMICAL BIOLOGY
  • 2014-04. Broad specificity profiling of TALENs results in engineered nucleases with improved DNA-cleavage specificity in NATURE METHODS
  • 2016-03. Enhancing homology-directed genome editing by catalytically active and inactive CRISPR-Cas9 using asymmetric donor DNA in NATURE BIOTECHNOLOGY
  • 2015-02. Therapeutic genome editing: prospects and challenges in NATURE MEDICINE
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ncomms15790

    DOI

    http://dx.doi.org/10.1038/ncomms15790

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1085880702

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/28585549


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