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GFP-on mouse model for interrogation of in vivo gene editing

Author

Listed:
  • Carla Dib

    (Stanford University School of Medicine
    Stanford University)

  • Jack A. Queenan

    (Broad Institute of MIT and Harvard
    Harvard University
    Harvard University)

  • Leah Swartzrock

    (Stanford University School of Medicine
    Stanford University)

  • Hana Willner

    (Stanford University School of Medicine
    Stanford University)

  • Morgane Denis

    (Stanford University School of Medicine
    Stanford University)

  • Nouraiz Ahmed

    (Broad Institute of MIT and Harvard
    Harvard University
    Harvard University)

  • Fareha Moulana Zada

    (University of California San Francisco
    University of California San Francisco
    University of California San Francisco)

  • Beltran Borges

    (University of California San Francisco
    University of California San Francisco
    University of California San Francisco)

  • Carsten T. Charlesworth

    (Stanford University)

  • Tony Lum

    (University of California San Francisco
    University of California San Francisco
    University of California San Francisco)

  • Bradley P. Yates

    (Johns Hopkins University School of Medicine)

  • Caleb Y. Kwon

    (Thayer School of Engineering)

  • Augustino V. Scorzo

    (Thayer School of Engineering)

  • Scott C. Davis

    (Thayer School of Engineering)

  • Jessie R. Davis

    (Broad Institute of MIT and Harvard
    Harvard University
    Harvard University)

  • Ran He

    (University of Massachusetts Chan Medical School
    University of Massachusetts Chan Medical School)

  • Jun Xie

    (University of Massachusetts Chan Medical School
    University of Massachusetts Chan Medical School
    University of Massachusetts Chan Medical School
    University of Massachusetts Chan Medical School)

  • Guangping Gao

    (University of Massachusetts Chan Medical School
    University of Massachusetts Chan Medical School
    University of Massachusetts Chan Medical School
    University of Massachusetts Chan Medical School)

  • Tippi C. MacKenzie

    (University of California San Francisco
    University of California San Francisco
    University of California San Francisco)

  • David R. Liu

    (Broad Institute of MIT and Harvard
    Harvard University
    Harvard University)

  • Gregory A. Newby

    (Broad Institute of MIT and Harvard
    Harvard University
    Harvard University
    Johns Hopkins University School of Medicine)

  • Agnieszka D. Czechowicz

    (Stanford University School of Medicine
    Stanford University)

Abstract

Gene editing technologies have revolutionized therapies for numerous genetic diseases. However, in vivo gene editing hinges on identifying efficient delivery vehicles for editing in targeted cell types, a significant hurdle in fully realizing its therapeutic potential. A model system to rapidly evaluate systemic gene editing would advance the field. Here, we develop the GFP-on reporter mouse, which harbors a nonsense mutation in a genomic EGFP sequence correctable by adenine base editor (ABE) among other genome editors. The GFP-on system was validated using single and dual adeno-associated virus (AAV9) encoding ABE8e and sgRNA. Intravenous administration of AAV9-ABE8e-sgRNA into adult GFP-on mice results in EGFP expression consistent with the tropism of AAV9. Intrahepatic delivery of AAV9-ABE8e-sgRNA into GFP-on fetal mice restores EGFP expression in AAV9-targeted organs lasting at least six months post-treatment. The GFP-on model provides an ideal platform for high-throughput evaluation of emerging gene editing tools and delivery modalities.

Suggested Citation

  • Carla Dib & Jack A. Queenan & Leah Swartzrock & Hana Willner & Morgane Denis & Nouraiz Ahmed & Fareha Moulana Zada & Beltran Borges & Carsten T. Charlesworth & Tony Lum & Bradley P. Yates & Caleb Y. K, 2025. "GFP-on mouse model for interrogation of in vivo gene editing," Nature Communications, Nature, vol. 16(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-61449-y
    DOI: 10.1038/s41467-025-61449-y
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