Li Guangyao, Li Shengju, Ye Fangzhou, Chen Keguang, Yu Hongmeng
Department of Otolaryngology, Eye & ENT Hospital, Fudan University, Shanghai, People's Republic of China.
Department of Otorhinolaryngology - Head and Neck Surgery, Shanghai Zhongshan Hospital Affiliated to Fudan University, Shanghai, People's Republic of China; and.
Am J Respir Cell Mol Biol. 2025 Aug;73(2):310-321. doi: 10.1165/rcmb.2025-0085OC.
Allergic rhinitis (AR) is a prevalent chronic condition that significantly impacts patients' quality of life and strains healthcare systems. Current treatments, primarily involving therapeutic proteins such as antibodies and cytokines, have limitations, including injection requirements, short half-lives, and potential side effects. This study developed an indole-induced transgene system (ITS), utilizing the olfactory receptor Olfr205 to activate gene expression in response to indole. Incorporated in an adeno-associated virus vector, the ITS was tested in a mouse model of AR, with functionality assessed through experiments in Hana3A cells and studies. Cellular assays, flow cytometry, ELISA, and histopathological analyses were used to measure therapeutic protein expression, immune cell profiles, inflammatory cytokines, IgE levels, and tissue inflammation. The results demonstrated that the ITS effectively controlled gene expression, reduced inflammation, and improved tissue morphology, offering promise for targeted gene therapy in AR and other chronic inflammatory diseases.
变应性鼻炎(AR)是一种常见的慢性疾病,严重影响患者的生活质量并给医疗系统带来压力。目前的治疗方法主要涉及治疗性蛋白质,如抗体和细胞因子,但存在局限性,包括需要注射、半衰期短以及潜在的副作用。本研究开发了一种吲哚诱导转基因系统(ITS),利用嗅觉受体Olfr205响应吲哚激活基因表达。将ITS整合到腺相关病毒载体中,在AR小鼠模型中进行测试,并通过在Hana3A细胞中的实验和研究评估其功能。使用细胞分析、流式细胞术、酶联免疫吸附测定(ELISA)和组织病理学分析来测量治疗性蛋白质表达、免疫细胞谱、炎性细胞因子、免疫球蛋白E(IgE)水平和组织炎症。结果表明,ITS有效控制基因表达,减轻炎症并改善组织形态,为AR和其他慢性炎症性疾病的靶向基因治疗带来了希望。