腺病毒载体介导的毛细胞再生受启动子类型的影响。
Adenovector-mediated hair cell regeneration is affected by promoter type.
作者信息
Praetorius Mark, Hsu Chi, Baker Kim, Brough Douglas E, Plinkert Peter, Staecker Hinrich
机构信息
Department of Otolaryngology, University of Heidelberg, Heidelberg, Germany.
出版信息
Acta Otolaryngol. 2010 Feb;130(2):215-22. doi: 10.3109/00016480903019251.
CONCLUSION
Replacement of vestibular hair cells induced by atoh1 driven by the tissue-specific GFAP promoter was significantly more efficient than use of the cBA or hCMV promoter.
OBJECTIVE
To test whether expression level, persistence, or selectivity from adenovirus vectors delivered in the inner ear can be altered by changing the adenovector backbone or by using different cellular and viral promoters.
MATERIALS AND METHODS
Adenovector and promoter modifications were tested for differences in transgene expression in adult macular organs. The effect of using an E1/E3 deleted vector was compared to E1/E3/E4 deleted vectors. The effect of using viral and cellular promoters to modify transgene expression was tested in explanted adult mouse macular organs. Based on these results three different promoters were tested for efficacy of atonal gene.
RESULTS
Use of adenovectors containing human CMV, the hybrid cBA and ubiquitin promoters driving transgene expression resulted in different types of transgene expression. While several viral and cellular promoters provided broad cell type expression, expression driven by the GFAP promoter was limited to vestibular supporting cells, demonstrating the specificity of this promoter.
结论
由组织特异性GFAP启动子驱动的atoh1诱导的前庭毛细胞替代比使用cBA或hCMV启动子显著更有效。
目的
测试通过改变腺病毒载体骨架或使用不同的细胞和病毒启动子，是否可以改变内耳中递送的腺病毒载体的表达水平、持久性或选择性。
材料与方法
测试腺病毒载体和启动子修饰在成年黄斑器官中转基因表达的差异。将使用E1/E3缺失载体的效果与E1/E3/E4缺失载体进行比较。在成年小鼠黄斑器官外植体中测试使用病毒和细胞启动子修饰转基因表达的效果。基于这些结果，测试了三种不同的启动子对无调性基因的功效。
结果
使用包含人CMV、驱动转基因表达的杂交cBA和泛素启动子的腺病毒载体导致了不同类型的转基因表达。虽然几种病毒和细胞启动子提供了广泛的细胞类型表达，但由GFAP启动子驱动的表达仅限于前庭支持细胞，证明了该启动子的特异性。
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