1. ¹Department of Orthodontics and Dentofacial Orthopedics, Graduate School of Dentistry, The University of Tokushima, Tokushima, Japan
2. ²Department of Internal Medicine, Division of Neurology, Kawasaki Medical School, Okayama, Japan
3. ³Department of Oral Molecular Pathology, Institute of Health Bioscience, The University of Tokushima Graduate School, Tokushima, Japan
4. ⁴Department of Life Systems, Institute of Technology and Science, The University of Tokushima, Tokushima, Japan

Correspondence: Professor S Noji, Department of Life Systems, Institute of Technology and Science, The University of Tokushima, 2-1 Minami-Jyosanjima-cho, Tokushima 770-8506, Japan. E-mails: noji@bio.tokushima-u.ac.jp; Dr H Ohuchi, hohuchi@bio.tokushima-u.ac.jp

⁵Current address: Department of Maxillofacial Orthognathics, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.

Received 10 October 2007; Revised 26 November 2007; Accepted 23 January 2008; Published online 6 March 2008.

Abstract

RNA interference (RNAi) offers a novel therapeutic strategy based on the highly specific and efficient silencing of a target gene. Since it relies on small interfering RNAs (siRNAs), a major issue is the delivery of therapeutically active siRNAs into the target tissue/target cells in vivo. For safety reasons, strategies based on vector delivery may be of only limited clinical use. The more desirable approach is to directly apply active siRNAs in vivo. Here, we report the effectiveness of in vivo siRNA delivery into skeletal muscles of normal or diseased mice through nanoparticle formation of chemically unmodified siRNAs with atelocollagen (ATCOL). ATCOL-mediated local application of siRNA targeting myostatin, a negative regulator of skeletal muscle growth, in mouse skeletal muscles or intravenously, caused a marked increase in the muscle mass within a few weeks after application. These results imply that ATCOL-mediated application of siRNAs is a powerful tool for future therapeutic use for diseases including muscular atrophy.