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

Miracure Inc., Tokyo, JapanRecent advances of biotechnology have laid the groundworkfor potent and specific molecular-targeting therapies includingRNA interference. The largest remaining hurdle for wide-spread use of this technology in skin is an effective deliverysystem. Here, we demonstrate an effective topical deliverysystem using a cream formulation containing a small-interfering RNA (siRNA) that specifically targets osteopontin(OPN). OPN is a validated target in numerous inflammatorydiseases, including rheumatoid arthritis (RA). The siRNAtargeting OPN was incorporated into a cream formulationGeneCream that penetrates the stratum corneum, depositingsiRNA in the epidermis, dermis, and to a lesser extent,subcutaneous tissue. In addition, when the OPN siRNA creamwas topically applied to the skin of a collagen antibody-induced RA mouse model, the siRNA cream prevented theoccurrence of severe, irreversible damage to bone andcartilage. Thus, the siRNA cream provides effective deliveryof active OPN siRNA, suggesting this formulation mayrepresent a platform technology for delivery of siRNAs fortreating various disorders including RA.Gene Therapy (2009) 16, 982–989; doi:10.1038/gt.2009.66;published online 28 May 2009Keywords: siRNA cream; osteopontin; rheumatoid arthritis