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Updated: Sep 25, 2025

Vasodilation of Isolated Vessels and the Isolation of the Extracellular Matrix of Tight-skin Mice
Published on: March 24, 2017
RNAi-based modulation of IFN-γ signaling in skin
Qi Tang1, Jacquelyn Sousa2, Dimas Echeverria2
1RNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA; Department of Dermatology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.
Abstract:
Aberrant activation of interferon (IFN)-γ signaling plays a key role in several autoimmune skin diseases, including lupus erythematosus, alopecia areata, vitiligo, and lichen planus. Here, we identify fully chemically modified small interfering RNAs (siRNAs) that silence the ligand binding chain of the IFN-γ receptor (IFNGR1), for the modulation of IFN-γ signaling. Conjugating these siRNAs to docosanoic acid (DCA) enables productive delivery to all major skin cell types local to the injection site, with a single dose of injection supporting effective IFNGR1 protein reduction for at least 1 month in mice. In an ex vivo model of IFN-γ signaling, DCA-siRNA efficiently inhibits the induction of IFN-γ-inducible chemokines, CXCL9 and CXCL10, in skin biopsies from the injection site. Our data demonstrate that DCA-siRNAs can be engineered for functional gene silencing in skin and establish a path toward siRNA treatment of autoimmune skin diseases.
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