Myostatin Gene Editing Across Vertebrates, Comparative Insights from CRISPR, TALENs, and AAV-Mediated Strategies

Abstract

Myostatin (MSTN/GDF-8) is a conserved negative regulator of skeletal muscle growth in vertebrates. Recent advances in genome-editing technologies, including CRISPR/Cas9, TALENs, and AAV-mediated approaches, have enabled precise MSTN knockout across mammals, fish, and avian species. MSTN inhibition consistently enhances muscle mass through hyperplasia and hypertrophy, elevates myogenic transcription factors such as MyoD and Myf5, and modulates metabolic pathways, including glucose homeostasis and adipose deposition. MSTN knockout also affects systemic physiology, including the gut–muscle axis, bone density, and neuromuscular function, revealing pleiotropic effects beyond muscle growth. Comparative studies in rabbits, pigs, channel catfish, zebrafish, chickens, and mice demonstrate species-specific outcomes, highlighting the importance of tailored strategies for therapeutic or agricultural applications. While MSTN-targeted interventions show promise for muscle-wasting disorders, sarcopenia, Duchenne muscular dystrophy, and cultured-meat production, challenges remain, including off-target effects, reproductive and skeletal trade-offs, and limited clinical translation. This review synthesizes recent research on MSTN knockout, emphasizing conserved mechanisms, phenotypic consequences, and translational potential, providing a framework for future studies aimed at safely exploiting MSTN inhibition to enhance muscle mass and metabolic health.