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AUF1 mRNA binding protein therapy in severe muscle injury blocks atrophy, accelerates regeneration and neuromuscular junction formation

ABSTRACT: There are currently no approved therapeutic interventions to promote skeletal muscle regeneration following traumatic muscle injury, among the most common debilitating injuries. Here we developed a new therapeutic approach for severe muscle injury that significantly prevents muscle atrophy, while promoting rapid muscle repair, regeneration and regeneration of neuro-muscular junctions (NMJs), orchestrated by gene delivery of the mRNA binding protein AUF1. Key regulators of myogenesis and NMJs are encoded by mRNAs that are regulated in their stability and translation by AUF1. Using preclinical mouse models of severe muscle injury, we show that delivery of the AUF1 gene to muscle cells systemically or intramuscularly by AAV8 or lentivirus vectors, prophylactically, during or 24 hours after injury, is highly effective in reducing muscle atrophy, rapidly expanding muscle stem cells, promoting accelerated muscle repair, regeneration and maturation, while restoring NMJs. Animals receiving AUF1 therapy following severe tibialis anterior muscle injury, rapidly regained near-normal muscle strength and function by two weeks, whereas control animals showed continued significant deficit four months later. Histologic and ultrastructure electron micrographic analysis shows that AUF1 gene therapy restores normal muscle architecture and muscle mass. AUF1 therapy is a potential new approach for treating severe muscle injury.

ORGANISM(S): Mus musculus

PROVIDER: GSE264682 | GEO | 2026/03/01

REPOSITORIES: GEO

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AUF1 mRNA binding protein therapy in severe muscle injury blocks atrophy, accelerates regeneration and neuromuscular junction formation

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