Gene silencing of STAT6 with siRNA ameliorates contact hypersensitivity and allergic rhinitis

Abstract

Local administration of STAT6 siRNA is thus a promising therapeutic strategy for both Th2-mediated cutaneous diseases and allergic rhinitis.

Protective Role of STAT6 in Basophil-Dependent Prurigo-like Allergic Skin Inflammation

“…Previously, we demonstrated amelioration of contact hypersensitivity and allergic rhinitis by local administration of STAT6 siRNA and in STAT6-deficient mice (24,31). We also reported the clinical benefits of STAT6-decoy oligodeoxynucleotide ointment in treating atopic dermatitis (50).…”

“…Mice were transfected with siRNA by injection into each ear lobe to a final concentration of 0.5 nmol/30 ml/ear diluted with Life Technologies Opti-MEM I (Invitrogen)/Lipofectamine 2000 at a ratio of 50:1 (31). The nucleotide sequences of the sense and antisense strands of mouse STAT6 siRNA were 59-CGAAUGUGAUACAACUGUAUC-39 and 59-UACAGUUGUAUCACAUUCGAG-39, respectively.…”

Gene Therapy for Allergic Airway Diseases

“…In an in vivo murine model, intranasal administration of naked siRNA against STAT6 to sensitized animals right before and during allergen challenge significantly inhibited the development of allergen-induced airway inflammation, goblet cell hyperplasia, and AHR [25•]. Also, in an in vivo allergic rhinitis model, the therapeutic potential to target STAT6 was demonstrated [26]. These preclinical studies suggest that STAT6 is a promising target for treatment of allergic airway diseases, but thus far, no clinical trials have been published using this approach.…”

Strategies targeting the IL-4/IL-13 axes in disease

“…IL-4 and IL-13 signaling was prevented using STAT6 siRNA in a mouse systemic sensitization and nasal challenge model. When dosed during the nasal allergen challenge period STAT6 siRNA prevented allergen induced sneezing, nasal rubbing, ablated IL-4 and IL-5 production from ex vivo allergen challenged lymph node cells and reduced nasal mononuclear and eosinophil infiltration by approximately 50% [246].…”