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Therapeutic silencing of an endogenous gene by siRNA cream in an arthritis model mouse

Gene Therapy volume 16, pages 982–989 (2009)Cite this article

Abstract

Recent advances of biotechnology have laid the groundwork for potent and specific molecular-targeting therapies including RNA interference. The largest remaining hurdle for widespread use of this technology in skin is an effective delivery system. Here, we demonstrate an effective topical delivery system using a cream formulation containing a small-interfering RNA (siRNA) that specifically targets osteopontin (OPN). OPN is a validated target in numerous inflammatory diseases, including rheumatoid arthritis (RA). The siRNA targeting OPN was incorporated into a cream formulation GeneCream that penetrates the stratum corneum, depositing siRNA in the epidermis, dermis, and to a lesser extent, subcutaneous tissue. In addition, when the OPN siRNA cream was topically applied to the skin of a collagen antibody-induced RA mouse model, the siRNA cream prevented the occurrence of severe, irreversible damage to bone and cartilage. Thus, the siRNA cream provides effective delivery of active OPN siRNA, suggesting this formulation may represent a platform technology for delivery of siRNAs for treating various disorders including RA.

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Acknowledgements

This study was supported by grants-in-aids from the Ministry of Education, Culture, Sports, Science and Technology of Japan; the Ministry of Health, Labour and Welfare of Japan; Japan Health Sciences Foundation; a grant from Yamaguchi Endocrine Research Association and the grant from ‘University–Industry Joint Research Project’ for private universities as well as a matching fund subsidy from the MEXT (Ministry of Education, Culture, Sports, Science and Technology, 2007–2009).

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Authors and Affiliations

  1. Department of Pathology, Tokyo Medical University, Tokyo, Japan

    M Takanashi, K Oikawa, M Tanaka, K Fujita, A Ishikawa, M Kudo & M Kuroda

  2. Department of Cell Therapy, Tokyo Medical University, Tokyo, Japan

    M Takanashi & K Oikawa

  3. Animal Resarch Center, Tokyo Medical University, Tokyo, Japan

    K Sudo

  4. Frontier Research Initiative, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan

    S Nakae

  5. TransDerm Inc., Santa Cruz, CA, USA

    R L Kaspar

  6. Miracure Inc., Tokyo, Japan

    M Matsuzaki

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  1. M Takanashi
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Correspondence to M Kuroda.

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Takanashi, M., Oikawa, K., Sudo, K. et al. Therapeutic silencing of an endogenous gene by siRNA cream in an arthritis model mouse. Gene Ther 16, 982–989 (2009). https://doi.org/10.1038/gt.2009.66

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  • DOI: https://doi.org/10.1038/gt.2009.66

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