IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v12y2021i1d10.1038_s41467-021-23996-y.html
   My bibliography  Save this article

Efficient precise in vivo base editing in adult dystrophic mice

Author

Listed:
  • Li Xu

    (The Ohio State University Wexner Medical Center)

  • Chen Zhang

    (The Ohio State University Wexner Medical Center)

  • Haiwen Li

    (The Ohio State University Wexner Medical Center)

  • Peipei Wang

    (The Ohio State University Wexner Medical Center)

  • Yandi Gao

    (The Ohio State University Wexner Medical Center)

  • Nahush A. Mokadam

    (The Ohio State University Wexner Medical Center)

  • Jianjie Ma

    (The Ohio State University Wexner Medical Center)

  • W. David Arnold

    (The Ohio State University Wexner Medical Center)

  • Renzhi Han

    (The Ohio State University Wexner Medical Center)

Abstract

Recent advances in base editing have created an exciting opportunity to precisely correct disease-causing mutations. However, the large size of base editors and their inherited off-target activities pose challenges for in vivo base editing. Moreover, the requirement of a protospacer adjacent motif (PAM) nearby the mutation site further limits the targeting feasibility. Here we modify the NG-targeting adenine base editor (iABE-NGA) to overcome these challenges and demonstrate the high efficiency to precisely edit a Duchenne muscular dystrophy (DMD) mutation in adult mice. Systemic delivery of AAV9-iABE-NGA results in dystrophin restoration and functional improvement. At 10 months after AAV9-iABE-NGA treatment, a near complete rescue of dystrophin is measured in mdx4cv mouse hearts with up to 15% rescue in skeletal muscle fibers. The off-target activities remains low and no obvious toxicity is detected. This study highlights the promise of permanent base editing using iABE-NGA for the treatment of monogenic diseases.

Suggested Citation

  • Li Xu & Chen Zhang & Haiwen Li & Peipei Wang & Yandi Gao & Nahush A. Mokadam & Jianjie Ma & W. David Arnold & Renzhi Han, 2021. "Efficient precise in vivo base editing in adult dystrophic mice," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23996-y
    DOI: 10.1038/s41467-021-23996-y
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-021-23996-y
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-021-23996-y?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. Haiwen Li & Peipei Wang & Chen Zhang & Yuanbojiao Zuo & Yuan Zhou & Renzhi Han, 2023. "Defective BVES-mediated feedback control of cAMP in muscular dystrophy," Nature Communications, Nature, vol. 14(1), pages 1-14, 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:12:y:2021:i:1:d:10.1038_s41467-021-23996-y. 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.