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Atelocollagen-mediated local and systemic applications of myostatin-targeting siRNA increase skeletal muscle mass

Gene Therapy volume 15, pages 1126–1130 (2008)Cite this article

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.

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Acknowledgements

We thank Drs Shin-ichiro Nishimatsu, Tsutomu Nohno, Department of Molecular Biology, Kawasaki Medical School for valuable advice. We also thank Shizuka Sasano, Division of Neurology, Kawasaki Medical School and Megumu Kita, Laboratory Animal Center, Kawasaki Medical School for their technical assistances. This work was supported by a Research Grant (14B-4) for Nervous and Mental Disorders from the Ministry of Health, Labour and Welfare; a Grant (15131301) for Research on Psychiatric and Neurological Diseases and Mental Health from the Ministry of Health, Labour and Welfare of Japan and from JSPS KAKENHI (14370212) to SN, YO and YS and by Research Project Grants (15-115B and 16-601) from Kawasaki Medical School to YO and YS.

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Author notes

  1. K Moriyama

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

Authors and Affiliations

  1. Department of Orthodontics and Dentofacial Orthopedics, Graduate School of Dentistry, The University of Tokushima, Tokushima, Japan

    N Kinouchi, Y Tanimoto & K Moriyama

  2. Department of Internal Medicine, Division of Neurology, Kawasaki Medical School, Okayama, Japan

    Y Ohsawa & Y Sunada

  3. Department of Oral Molecular Pathology, Institute of Health Bioscience, The University of Tokushima Graduate School, Tokushima, Japan

    N Ishimaru & Y Hayashi

  4. Department of Life Systems, Institute of Technology and Science, The University of Tokushima, Tokushima, Japan

    H Ohuchi & S Noji

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  1. N Kinouchi
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  2. Y Ohsawa
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  3. N Ishimaru
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  4. H Ohuchi
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  7. Y Tanimoto
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Corresponding authors

Correspondence to H Ohuchi or S Noji.

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Supplementary Information accompanies the paper on Gene Therapy website (http://www.nature.com/gt)

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Kinouchi, N., Ohsawa, Y., Ishimaru, N. et al. Atelocollagen-mediated local and systemic applications of myostatin-targeting siRNA increase skeletal muscle mass. Gene Ther 15, 1126–1130 (2008). https://doi.org/10.1038/gt.2008.24

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  • DOI: https://doi.org/10.1038/gt.2008.24

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