Engineered Circular RNA CircmiR-29b Attenuates Muscle Atrophy by Sponging MiR-29b

Muscle atrophy is commonly caused by various diseases but still lacks effective treatment in clinical practice. Here, an artificial circular RNA (circRNA) named circmiR-29b, which is designed to be a molecular sponge for miR-29b containing 12 imperfect bulged miR-29b binding sites is constructed. CircmiR-29b shows a favorable functional effect with respect to miR-29b repression in a specific and drastic manner. CircmiR-29b can protect against in vitro muscle atrophy induced by dexamethasone (Dex), angiotensin II (Ang II), and tumor necrosis factor alpha (TNF-α). Besides, circmiR-29b attenuates in vivo muscle atrophy induced by denervation, immobilization, and Ang II. More importantly, skeletal muscle specific gene therapy using circmiR-29b is able to attenuate established muscle atrophy induced by spiral wire immobilization. This work has developed an engineered circmiR-29b acting as an miR-29b sponge, and offers a promising therapeutic tool to prevent muscle atrophy.