Topical Application of siRNA Targeting Cutaneous Dendritic Cells in Allergic Skin Disease
RNA interference is a promising method for silencing specific genes and has great potential for therapeutic applications. However, the major hurdle for therapeutic application is the limited stability of double-strand RNA (dsRNA) and the absence of a reliable delivery method to target cells. Skin appears to be a favorable target for small interfering RNA (siRNA) therapy. Dendritic cells (DCs) exist in the skin and mucosae on the front lines of defense; these cells capture antigens and play a crucial role in inducing immunity and tolerance.
In our recent work, we have shown a successful treatment using CD86 siRNA targeting cutaneous DCs. A costimulatory molecule, CD86, is induced on DCs in situ after antigen uptake, and CD86-expressing DCs migrate to the regional lymph nodes to present antigens to T cells. Topical application of cream-emulsified CD86 siRNA ameliorated the clinical manifestations in murine contact hypersensitivity (CH) and atopic dermatitis (AD)-like disease. Our method may be advantageous for the treatment of allergic skin diseases.
Key wordsDendritic cells siRNA Topical application CD86 Costimulatory molecules Skin allergic disease
This work was supported by a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
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