Effectiveness of cationic liposome‐mediated local delivery of myostatin‐targeting small interfering RNA in vivo

This study evaluated the effectiveness of local administration of cationic liposome-delivered myostatin-targeting siRNA. Myostatin (Mst)-siRNA and scrambled (scr)-siRNA-lipoplexes were injected into the masseter muscles of wild type and dystrophin-deficient mdx mice, which model Duchenne muscular dystrophy. One week after injection, the masseter muscles were dissected for histometric analyses. To evaluate changes in masseter muscle activity, masseter electromyographic (EMG) measurements were performed. One week after local administration of Mst-siRNA-lipoplexes, masseter muscles and myofibrils were significantly larger compared to control masseter muscles treated with scr-siRNA-lipoplexes. Real-time polymerase chain reaction (PCR) analyses revealed significant upregulation of the myogenic regulatory factors MyoD and myogenin and significant downregulation of the adipogenic transcription factors peroxisome proliferator-activated receptor-γ (PPARγ) and CCAAT/enhancer binding protein-α (CEBPα) in masseter muscles treated with Mst-siRNA-lipoplexes. The duty times of masseter muscle activity exceeding 5% showed a slight tendency to increase in both wild type and mdx mice. Therefore, cationic liposome-mediated local administration of Mst-siRNA could increase muscular size and improve muscle activity. Since cationic liposomes delivered siRNA to muscles effectively and are safe and cost-effective, they may represent a therapeutic tool for use in treating muscular diseases.