IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v475y2011i7355d10.1038_nature10177.html
   My bibliography  Save this article

In vivo genome editing restores haemostasis in a mouse model of haemophilia

Author

Listed:
  • Hojun Li

    (CTRB 5000, Children’s Hospital of Philadelphia, 3501 Civic Center Boulevard)

  • Virginia Haurigot

    (CTRB 5000, Children’s Hospital of Philadelphia, 3501 Civic Center Boulevard)

  • Yannick Doyon

    (Sangamo BioSciences, Point Richmond Tech Center, 501 Canal Boulevard, Suite A100, Richmond, California 94804, USA)

  • Tianjian Li

    (Sangamo BioSciences, Point Richmond Tech Center, 501 Canal Boulevard, Suite A100, Richmond, California 94804, USA)

  • Sunnie Y. Wong

    (Sangamo BioSciences, Point Richmond Tech Center, 501 Canal Boulevard, Suite A100, Richmond, California 94804, USA)

  • Anand S. Bhagwat

    (CTRB 5000, Children’s Hospital of Philadelphia, 3501 Civic Center Boulevard)

  • Nirav Malani

    (426 Johnson Pavilion, University of Pennsylvania School of Medicine, 3610 Hamilton Walk, Philadelphia, Pennsylvania 19104, USA)

  • Xavier M. Anguela

    (CTRB 5000, Children’s Hospital of Philadelphia, 3501 Civic Center Boulevard)

  • Rajiv Sharma

    (CTRB 5000, Children’s Hospital of Philadelphia, 3501 Civic Center Boulevard)

  • Lacramiora Ivanciu

    (CTRB 5000, Children’s Hospital of Philadelphia, 3501 Civic Center Boulevard)

  • Samuel L. Murphy

    (CTRB 5000, Children’s Hospital of Philadelphia, 3501 Civic Center Boulevard)

  • Jonathan D. Finn

    (CTRB 5000, Children’s Hospital of Philadelphia, 3501 Civic Center Boulevard)

  • Fayaz R. Khazi

    (CTRB 5000, Children’s Hospital of Philadelphia, 3501 Civic Center Boulevard)

  • Shangzhen Zhou

    (CTRB 5000, Children’s Hospital of Philadelphia, 3501 Civic Center Boulevard)

  • David E. Paschon

    (Sangamo BioSciences, Point Richmond Tech Center, 501 Canal Boulevard, Suite A100, Richmond, California 94804, USA)

  • Edward J. Rebar

    (Sangamo BioSciences, Point Richmond Tech Center, 501 Canal Boulevard, Suite A100, Richmond, California 94804, USA)

  • Frederic D. Bushman

    (426 Johnson Pavilion, University of Pennsylvania School of Medicine, 3610 Hamilton Walk, Philadelphia, Pennsylvania 19104, USA)

  • Philip D. Gregory

    (Sangamo BioSciences, Point Richmond Tech Center, 501 Canal Boulevard, Suite A100, Richmond, California 94804, USA)

  • Michael C. Holmes

    (Sangamo BioSciences, Point Richmond Tech Center, 501 Canal Boulevard, Suite A100, Richmond, California 94804, USA)

  • Katherine A. High

    (CTRB 5000, Children’s Hospital of Philadelphia, 3501 Civic Center Boulevard
    Howard Hughes Medical Institute, 415 Curie Boulevard)

Abstract

Gene correction in a blood disorder Direct editing of disease-causing mutations has obvious attractions for the treatment of genetic disorders if the many practical obstacles to the technique can be overcome. One promising line of research centres on the development of zinc finger nucleases (ZFNs) produced by fusing an engineered zinc finger DNA-binding domain to an endonuclease. These artificial enzymes induce efficient gene correction in cultured cells. Li et al. now report that zinc finger nucleases induce double-strand breaks in specifically selected locations on the genome and stimulate genome editing at a clinically meaningful level in vivo. In a proof-of-principle experiment, ZFNs delivered to the liver in a mouse model of haemophilia B achieved a level of gene replacement that was sufficient to correct the clotting defect, and the effect persisted following liver regeneration.

Suggested Citation

  • Hojun Li & Virginia Haurigot & Yannick Doyon & Tianjian Li & Sunnie Y. Wong & Anand S. Bhagwat & Nirav Malani & Xavier M. Anguela & Rajiv Sharma & Lacramiora Ivanciu & Samuel L. Murphy & Jonathan D. F, 2011. "In vivo genome editing restores haemostasis in a mouse model of haemophilia," Nature, Nature, vol. 475(7355), pages 217-221, July.
    • Handle: RePEc:nat:nature:v:475:y:2011:i:7355:d:10.1038_nature10177
    DOI: 10.1038/nature10177
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/nature10177
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1038/nature10177?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
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

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


    Cited by:

    1. Patrizia Tornabene & Rita Ferla & Manel Llado-Santaeularia & Miriam Centrulo & Margherita Dell’Anno & Federica Esposito & Elena Marrocco & Emanuela Pone & Renato Minopoli & Carolina Iodice & Edoardo N, 2022. "Therapeutic homology-independent targeted integration in retina and liver," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    2. Xiangjun He & Zhenjie Zhang & Junyi Xue & Yaofeng Wang & Siqi Zhang & Junkang Wei & Chenzi Zhang & Jue Wang & Brian Anugerah Urip & Chun Christopher Ngan & Junjiang Sun & Yuefeng Li & Zhiqian Lu & Hui, 2022. "Low-dose AAV-CRISPR-mediated liver-specific knock-in restored hemostasis in neonatal hemophilia B mice with subtle antibody response," Nature Communications, Nature, vol. 13(1), pages 1-17, 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:nature:v:475:y:2011:i:7355:d:10.1038_nature10177. 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.