No abstract

Muscle atrophy is a frequently observed complication, characterized by the loss of muscle mass and strength, which diminishes the quality of life and survival. No effective therapy except exercise is currently available. In our previous study, repressing miR-29b has been shown to reduce muscle atrophy. In our current study, we have constructed artificially engineered extracellular vesicles for the delivery of CRISPR/Cas9 to target miR-29b (EVs-Cas9-29b). EVs-Cas9-29b has shown a favorable functional effect with respect to miR-29b repression in a specific and rapid manner by gene editing. In in vitro conditions, EVs-Cas9-29b could protect against muscle atrophy induced by dexamethasone (Dex), angiotensin II (AngII), and tumor necrosis factor-alpha (TNF-α). And EVs-Cas9-29b introduced in vivo preserved muscle function in the well-established immobilization and denervation-induced muscle atrophy mice model. Our work demonstrates an engineered extracellular vesicles delivery of the miR-29b editing system, which could be potentially used for muscle atrophy therapy.

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.