AAV9-EFS-SauriABE8e-U6-I276V-FKRP

AAV9-EFS-SauriABE8e-U6-I276V-FKRP is an experimental gene therapy designed to treat dystroglycanopathies caused by mutations in the fukutin-related protein (FKRP) gene, specifically the common C826A (L276I) point mutation. It utilizes a single adeno-associated virus serotype 9 (AAV9) vector to deliver a compact adenine base editor (SauriABE8e) under the control of an EFS promoter, along with a guide RNA (gRNA) under a U6 promoter. The therapy performs a precise A-to-G base edit to convert the mutant L276I FKRP into a functional L276V variant, thereby restoring functional glycosylation of alpha-dystroglycan (α-DG) and improving muscle integrity and function. Preclinical studies in mouse models have demonstrated that this single-vector system can achieve significant editing efficiency in heart and skeletal muscle, leading to improved respiratory and skeletal muscle function.