Exosome-mediated horizontal gene transfer occurs in double-strand break repair during genome editing View Full Text


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Article Info

DATE

2019-12

AUTHORS

Ryuichi Ono, Yukuto Yasuhiko, Ken-ichi Aisaki, Satoshi Kitajima, Jun Kanno, Yoko Hirabayashi

ABSTRACT

The CRISPR-Cas9 system has been successfully applied in many organisms as a powerful genome-editing tool. Undoubtedly, it will soon be applied to human genome editing, including gene therapy. We have previously reported that unintentional DNA sequences derived from retrotransposons, genomic DNA, mRNA and vectors are captured at double-strand breaks (DSBs) sites when DSBs are introduced by the CRISPR-Cas9 system. Therefore, it is possible that unintentional insertions associated with DSB repair represent a potential risk for human genome editing gene therapies. To address this possibility, comprehensive sequencing of DSB sites was performed. Here, we report that exosome-mediated horizontal gene transfer occurs in DSB repair during genome editing. Exosomes are present in all fluids from living animals, including seawater and breathing mammals, suggesting that exosome-mediated horizontal gene transfer is the driving force behind mammalian genome evolution. The findings of this study highlight an emerging new risk for this leading-edge technology. More... »

PAGES

57

References to SciGraph publications

  • 2010-12. Evaluation of Models of the Mechanisms Underlying Intron Loss and Gain in Aspergillus Fungi in JOURNAL OF MOLECULAR EVOLUTION
  • 2015-12. Double strand break repair by capture of retrotransposon sequences and reverse-transcribed spliced mRNA sequences in mouse zygotes in SCIENTIFIC REPORTS
  • 2015-05. Increasing the efficiency of precise genome editing with CRISPR-Cas9 by inhibition of nonhomologous end joining in NATURE BIOTECHNOLOGY
  • 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
  • 2018-12. Horizontal transfer of BovB and L1 retrotransposons in eukaryotes in GENOME BIOLOGY
  • 1996-10. Retrotransposon reverse-transcriptase-mediated repair of chromosomal breaks in NATURE
  • 1996-10. Capture of retrotransposon DNA at the sites of chromosomal double-strand breaks in NATURE
  • 2006-12. Annotation, submission and screening of repetitive elements in Repbase: RepbaseSubmitter and Censor in BMC BIOINFORMATICS
  • 2015-05. Increasing the efficiency of homology-directed repair for CRISPR-Cas9-induced precise gene editing in mammalian cells in NATURE BIOTECHNOLOGY
  • 2008-02. Role of retrotransposon-derived imprinted gene, Rtl1, in the feto-maternal interface of mouse placenta in NATURE GENETICS
  • 2007-06. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells in NATURE CELL BIOLOGY
  • 2006-01. Deletion of Peg10, an imprinted gene acquired from a retrotransposon, causes early embryonic lethality in NATURE GENETICS
  • Identifiers

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    http://scigraph.springernature.com/pub.10.1038/s42003-019-0300-2

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    http://dx.doi.org/10.1038/s42003-019-0300-2

    DIMENSIONS

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    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30775458


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    42 schema:description The CRISPR-Cas9 system has been successfully applied in many organisms as a powerful genome-editing tool. Undoubtedly, it will soon be applied to human genome editing, including gene therapy. We have previously reported that unintentional DNA sequences derived from retrotransposons, genomic DNA, mRNA and vectors are captured at double-strand breaks (DSBs) sites when DSBs are introduced by the CRISPR-Cas9 system. Therefore, it is possible that unintentional insertions associated with DSB repair represent a potential risk for human genome editing gene therapies. To address this possibility, comprehensive sequencing of DSB sites was performed. Here, we report that exosome-mediated horizontal gene transfer occurs in DSB repair during genome editing. Exosomes are present in all fluids from living animals, including seawater and breathing mammals, suggesting that exosome-mediated horizontal gene transfer is the driving force behind mammalian genome evolution. The findings of this study highlight an emerging new risk for this leading-edge technology.
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