Atopic dermatitis (AD) has high morbidity and poor prognosis because safe and effective treatments are scarce. Recently, siRNA has shown promise as an effective treatment to target specific aberrantly expressed genes. However, naked siRNAs are too inefficient due to various enzymatic, membrane, and cellular barriers. We previously reported that a Tat analog acting as a cell penetrating peptide, combined with AT1002, which reversibly increases paracellular transport of molecules across the epidermal barrier in epidermis-disrupted mice, enhances the skin permeation of water-soluble siRNA. In the present study, in order to develop a novel treatment for AD, we determined the intradermal permeation of siRNAs and the anti-allergic effects of a siRNA that silences RelA, a member of the NF- κB family, using Tat and AT1002 peptides in an AD mouse model. We first showed that the Tat analog and AT1002 delivered siRNA into the skin of ICR mice, and upon topical application to the AD-induced ears of NC/Nga mice, changed ZO-1 expression. In addition, the silencing effects on the mRNA of RelA in JAWS II cells transfected with siRelA, complexed with Tat, were as effective as a commercial vector. Furthermore, the ear thickness, clinical skin severity, topical cytokine levels, and serum IgE production in AD model mice treated with anti-RelA siRNA with Tat and AT1002 were improved.
- Received February 9, 2011.
- Revision received April 24, 2011.
- Accepted April 25, 2011.
- The American Society for Pharmacology and Experimental Therapeutics