CRISPR/Cas9 mediated miR-29b editing as a treatment of different types of muscle atrophy in mice

Abstract Muscle atrophy is the loss of skeletal muscle mass and strength in response to diverse catabolic stimuli. At present, no effective treatments except exercise has been shown to reduce muscle atrophy clinically. Here, we report that clustered regularly interspaced short palindromic repeat/Cas9 (CRISPR/Cas9) mediated genome editing through locally injection into gastrocnemius muscles or tibialis anterior muscle efficiently targets the biogenesis processing sites in pre-miR-29b. In vivo, this CRISPR-based treatment prevented the muscle atrophy induced by angiotensin II (AngII), immobilization and denervation via activation of AKT-FOXO3A-mTOR signaling pathway and protected against AngII-induced myocyte apoptosis in mice, leading to significantly increased exercise capacity. Our work establishes CRISPR/Cas9 based gene targeting on miRNA as a potential durable therapy for the treatment of muscle atrophy and expands the strategies available interrogating miRNA function in vivo.