1. ¹Department of Pathology, Tokyo Medical University, Tokyo, Japan
2. ²Department of Cell Therapy, Tokyo Medical University, Tokyo, Japan
3. ³Animal Resarch Center, Tokyo Medical University, Tokyo, Japan
4. ⁴Frontier Research Initiative, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
5. ⁵TransDerm Inc., Santa Cruz, CA, USA
6. ⁶Miracure Inc., Tokyo, Japan

Correspondence: Dr M Kuroda, Department of Pathology, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo, 160-8402, Japan. E-mail: kuroda@tokyo-med.ac.jp

Received 31 July 2008; Revised 9 February 2009; Accepted 10 February 2009; Published online 28 May 2009.

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.