development of gene therapy for auditory and vestibular disorders-gene delivery into the cochlear

听觉和前庭疾病基因治疗的发展-基因递送到耳蜗

• 批准号: 12557142
• 负责人: DOI Katsumi
• 金额: $ 7.81万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12557142/
• 关键词: adeno virus vector; HVJ-liposome; sensorineural hearing loss; gene delivery; klotho gene; 血管条; コルチ器; ラセン神経節細胞; 呼吸上皮; 水チャネル; 遺伝子導入; 鼻粘膜

Auditory function of klotho gene knock out (kl/kl) mouse was evaluated by measuring of ABR and EP of kl/kl mouse was significantly deteriorated compared with those of wild mouse, suggesting that kl/kl mouse has sensorineural hearing loss. RT-PCR and immunohistochemical analysis indicated that there was no expression of klotho mRNA and protein in the cochlea. The results suggest that klotho protein secreted from other tissues must reach to the cochlea via blood circulation and exert its physiological action there as a humoral factor essential for normal auditory function. Intra-cochlear and intra-cutaneous gene delivery of normal klotho gene with adeno virus vector (AVV) was found to be able to rescue completely the auditory function of kl/kl mouse. Gene delivery into the cochlea with HVJ-lipose was also found to be effective.

通过对klotho基因敲除（kl/kl）小鼠的ABR和EP测试，发现kl/kl小鼠的听功能较野生小鼠明显下降，提示kl/kl小鼠存在感音神经性听力损失。RT-PCR和免疫组化结果显示，耳蜗中无klotho mRNA和蛋白的表达。结果表明，从其他组织分泌的klotho蛋白必须通过血液循环到达耳蜗，并在那里发挥其生理作用，作为正常听觉功能所必需的体液因子。用腺病毒载体（AVV）经耳蜗内和皮肤内转染正常klotho基因，可完全恢复kl/kl小鼠的听觉功能。还发现用HVJ-脂质将基因递送到耳蜗中是有效的。