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

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

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 rap...

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Main Authors: 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. Kwon, Augustino V. Scorzo, Scott C. Davis, Jessie R. Davis, Ran He, Jun Xie, Guangping Gao, Tippi C. MacKenzie, David R. Liu, Gregory A. Newby, Agnieszka D. Czechowicz
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-61449-y
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Summary: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.
ISSN:2041-1723

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