IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v10y2019i1d10.1038_s41467-019-13342-8.html
   My bibliography  Save this article

Targeting specificity of APOBEC-based cytosine base editor in human iPSCs determined by whole genome sequencing

Author

Listed:
  • Erica McGrath

    (Food and Drug Administration)

  • Hyunsu Shin

    (Food and Drug Administration)

  • Linyi Zhang

    (Food and Drug Administration)

  • Je-Nie Phue

    (Food and Drug Administration)

  • Wells W. Wu

    (Food and Drug Administration)

  • Rong-Fong Shen

    (Food and Drug Administration)

  • Yoon-Young Jang

    (Johns Hopkins School of Medicine)

  • Javier Revollo

    (Food and Drug Administration)

  • Zhaohui Ye

    (Food and Drug Administration)

Abstract

DNA base editors have enabled genome editing without generating DNA double strand breaks. The applications of this technology have been reported in a variety of animal and plant systems, however, their editing specificity in human stem cells has not been studied by unbiased genome-wide analysis. Here we investigate the fidelity of cytidine deaminase-mediated base editing in human induced pluripotent stem cells (iPSCs) by whole genome sequencing after sustained or transient base editor expression. While base-edited iPSC clones without significant off-target modifications are identified, this study also reveals the potential of APOBEC-based base editors in inducing unintended point mutations outside of likely in silico-predicted CRISPR-Cas9 off-targets. The majority of the off-target mutations are C:G->T:A transitions or C:G->G:C transversions enriched for the APOBEC mutagenesis signature. These results demonstrate that cytosine base editor-mediated editing may result in unintended genetic modifications with distinct patterns from that of the conventional CRISPR-Cas nucleases.

Suggested Citation

  • Erica McGrath & Hyunsu Shin & Linyi Zhang & Je-Nie Phue & Wells W. Wu & Rong-Fong Shen & Yoon-Young Jang & Javier Revollo & Zhaohui Ye, 2019. "Targeting specificity of APOBEC-based cytosine base editor in human iPSCs determined by whole genome sequencing," Nature Communications, Nature, vol. 10(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-13342-8
    DOI: 10.1038/s41467-019-13342-8
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-019-13342-8
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-019-13342-8?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Ang Li & Hitoshi Mitsunobu & Shin Yoshioka & Takahisa Suzuki & Akihiko Kondo & Keiji Nishida, 2022. "Cytosine base editing systems with minimized off-target effect and molecular size," Nature Communications, Nature, vol. 13(1), pages 1-8, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-13342-8. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.