Gene therapy for a murine model of eosinophilic esophagitis

• DOI: 10.1111/all.14822
• Publication Date: 2021-03-22T08:12:25Z
• Authors: Anna E. Camilleri; Saparja Nag; Anthony R. Russo; Katie M. Stiles; Ronald G. Crystal; Odelya E. Pagovich
• Keywords: Eosinophilic Esophagitis

Eosinophils are specialized granulocytic effector cells that store and release highly active mediators used in immune defense. also implicated the pathogenesis of allergic disorders, including eosinophilic esophagitis (EoE), a chronic disorder characterized by infiltration eosinophils into esophagus damage tissue, resulting gastrointestinal morbidity, food impaction, dysphagia. Treatment with elimination diets and/or topical corticosteroid therapy slow disease progression, but complicated adverse effects, limited compliance, loss response to therapy. We hypothesized single administration an adeno-associated virus (AAV) coding for anti-eosinophil monoclonal antibody induces eosinophil clearance (anti-Siglec-F) would treat on persistent basis murine model EoE.A mouse peanut-induced EoE mimics human was established sensitization challenge peanut extract. After challenge, these mice exhibited phenotype demonstrated elevated levels blood eosinophils, associated esophageal remodeling impaction.The were treated intravenous (1011 genome copies) AAVrh.10mAnti-Eos, serotype rh.10 AAV vector anti-Siglec-F antibody. Vector resulted persistent, high expression. Administration AAVrh.10mAnti-Eos reduced (P < 0.02) numbers 0.002) protected from tissue minimized impaction.These results suggest treatment has potential provide therapeutic benefit patients EoE.