GFP-on mouse model for interrogation of in vivo gene editing
- 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
2025-07-31
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.