Precise selection-free DMD prime editing using high-capacity adenovectors
Prime editors have high potential for disease modelling and regenerative medicine efforts including those directed at the muscle-wasting disorder Duchenne muscular dystrophy (DMD) caused by the lack of dystrophin in striated muscle. However, the large size and multicomponent nature of prime editing systems poses substantial production and delivery issues especially when targeting hard-to-transfect dividing or quiescent cells. Here, we report that packaging optimized full-length prime editing constructs in adenoviral vector particles (AdVPs) permits installing precise DMD gene edits in human myogenic cells, namely, myoblasts and mesenchymal stem cells (up to 70-80% and 64% of target alleles, respectively).