Gene therapy in the inner ear. Mechanisms and clinical implications.
Gene therapy in the inner ear. Mechanisms and clinical implications.
复制标题
内耳基因治疗。
DOI：
10.1111/j.1749-6632.1999.tb08653.x
复制
发表时间：
1999
影响因子：
5.2
通讯作者：
Federoff,HJ
中科院分区：
文献类型：
--
作者：
VandeWater,TR;Staecker,H;Halterman,MW;Federoff,HJ
基因治疗在内耳的应用是一个新兴的研究领域。大多数研究报道了标记基因的表达（例如，半乳糖苷酶）。内耳组织的第一生物反应（即，听觉神经元）对表达治疗基因的基因治疗载体（含有BDNF基因的疱疹扩增子载体）转导的影响。这项研究很重要，因为它证明了基因增强方法治疗创伤性耳蜗的可行性。已使用腺病毒、腺相关病毒和疱疹扩增子载体获得耳蜗组织中转导或转染基因的长期表达。疱疹扩增子载体（即，HSVbdnflac）也已成功地用于支持听觉毛细胞丧失后听觉神经元在体内的存活（即，营养因子的丧失）。基因治疗已经成功地应用于实验室动物的耳蜗，未来的研究将确定载体和治疗基因的类型，这些类型将在临床上最好地用于治疗内耳疾病。
The application of gene therapy to the inner ear is an emerging field of study. Most studies report the expression of marker genes (e.g., galactosidase) within the tissues of the cochlea. The first biologic response of an inner ear tissue (i.e., auditory neurons) to transduction by a gene therapy vector expressing a therapeutic gene (a herpes amplicon vector containing a BDNF gene) was observed in spiral explants obtained from early postnatal rat cochleae. This study was important because it demonstrated the feasibility of a gene augmentation approach to treat traumatized cochleae. Long‐term expression of transduced or transfected genes in cochlear tissues have been obtained with adenovirus, adeno‐associated virus, and herpes amplicon vectors. The herpes amplicon vector (i.e.,HSVbdnflac) that evoked a biologic responsein vitrohas also been successfully used to support the survival of auditory neuronsin vivofollowing loss of the auditory hair cells (i.e., loss of trophic factor). Gene therapy has been successfully applied to the cochlea of a laboratory animal, and future studies will define the types of vectors and therapeutic genes that will work best for the treatment of inner ear diseases in the clinic.