title: Effectiveness of cationic liposome-mediated local delivery of myostatin-targeting small interfering RNA in vivo.
abstract: 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.
authors.affiliation: Department of Orthodontics and Dentofacial Orthopedics, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8504, Japan.
authors.forename: Hiroyo
authors.initials: H
authors.lastname: Mori
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Kawai
authors.forename: Nao
authors.initials: N
authors.lastname: Kinouchi
authors.forename: Natsuko
authors.initials: N
authors.lastname: Hichijo
authors.forename: Tatsuhiro
authors.initials: T
authors.lastname: Ishida
authors.forename: Emi
authors.initials: E
authors.lastname: Kawakami
authors.forename: Sumihare
authors.initials: S
authors.lastname: Noji
authors.forename: Eiji
authors.initials: E
authors.lastname: Tanaka
mesh_terms: D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D004576:Electromyography; D005786:Gene Expression Regulation / Q000187:drug effects*; D018390:Gene Targeting / Q000379:methods*; D018014:Gene Transfer Techniques; D008081:Liposomes; D008406:Masseter Muscle / Q000187:drug effects / Q000254:growth & development*; D051379:Mice; D018101:Mice, Inbred mdx; D055435:Myostatin / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism* / Q000494:pharmacology; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D022763:CCAAT-Enhancer-Binding Protein-alpha; D017931:DNA Primers; D008081:Liposomes; C525912:Mstn protein, mouse; D055435:Myostatin; D047495:PPAR gamma; D034741:RNA, Small Interfering
keywords: RNA interference; cationic liposome; muscular dystrophy; myostatin; small-interfering RNAs