Precision Genome Editing for Duchenne Muscular Dystrophy: Comparing AAV-Compatible Base and Prime Editors in a Humanized Mouse Model

Le September 30 2026 at 12h30 Séminaire

Duchenne muscular dystrophy (DMD) is a fatal pediatric disorder caused by the loss of dystrophin, a structural protein essential for muscle integrity. CRISPR-derived base and prime editors can directly correct disease-causing mutations in the genome; however, their clinical translation is limited by editing precision, off-target activity, and the cargo constraints of muscle-tropic AAV vectors. To benchmark these technologies under realistic conditions, we generated a fully humanized mouse model carrying a patient-derived nonsense variant in DMD that recapitulates the cardiac and skeletal muscle pathology of the disease. I will present a systematic comparison of base- and prime-editing strategies, ranging from engineered deaminases and guide RNA designs that maximize precision in patient-derived cells to a single systemic AAV treatment that restores up to 90% of dystrophin expression in the heart and improves both cardiac and skeletal muscle function in vivo. This work illustrates how humanized disease models can guide the selection and safe optimization of genome-editing technologies for clinical translation.