Ishibashi Yasuko, Zhu Jianliang, Gernoux Gwladys, Yu Yunkai, Suh Michelle J, Isgrig Kevin, Grati Mhamed, Olszewski Rafal, Hoa Michael, Liang Cao, Friedman Thomas B, Adjali Oumeya, Chien Wade W
Inner Ear Gene Therapy Program, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20892, USA.
Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20892, USA.
Mol Ther Methods Clin Dev. 2025 Mar 21;33(2):101456. doi: 10.1016/j.omtm.2025.101456. eCollection 2025 Jun 12.
Hearing loss is a common disability affecting the world's population. Currently, its treatment options are limited. Adeno-associated virus (AAV)-mediated inner ear gene therapy has shown great promise as a treatment for hereditary hearing loss. However, the host immune responses to AAV-mediated gene therapy in the mammalian inner ear is not well understood. In this study, two serotypes of AAV vectors were injected individually into the mouse inner ear to evaluate the host innate and adaptive immune responses up to 1 month after inner ear gene delivery. Our results suggest that the host innate and adaptive immune responses to AAV-mediated inner ear gene delivery are limited and mild, which is favorable for its clinical translation.
听力损失是一种影响全球人口的常见残疾。目前，其治疗选择有限。腺相关病毒（AAV）介导的内耳基因治疗作为遗传性听力损失的一种治疗方法已显示出巨大的前景。然而，哺乳动物内耳对AAV介导的基因治疗的宿主免疫反应尚不清楚。在本研究中，将两种血清型的AAV载体分别注射到小鼠内耳中，以评估内耳基因递送后长达1个月的宿主固有免疫和适应性免疫反应。我们的结果表明，宿主对AAV介导的内耳基因递送的固有免疫和适应性免疫反应是有限且轻微的，这有利于其临床转化。
