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腺病毒和腺相关病毒载体介导的基因转移至豚鼠耳蜗。

Adenoviral and adeno-associated viral vector mediated gene transfer in the guinea pig cochlea.

作者信息

Li Duan Mao, Bordet Thierry, Mezzina Mauro, Kahn Axel, Ulfendahl Mats

机构信息

Department of Clinical Neuroscience and Center for Hearing and Communication Research, Building M1-ENT, Karolinska Institutet, Karolinska Hospital, SE-171 76 Stockholm.

出版信息

Neuroreport. 2002 Jul 19;13(10):1295-9. doi: 10.1097/00001756-200207190-00016.

Abstract

Peripheral sensorineural hearing loss is a very common inner ear disorder affecting nearly 10% of the population. At present there is no cure for this disorder but gene therapy has been suggested as a potentially effective method for clinical treatment in the future. Thus we investigated the effectiveness of adenoviral (Ad) and adeno-associated viral (AAV) vectors to transduce the cochlea of guinea pigs. After direct injection into the basal turn of the cochlea, we found that both Ad and AAV vectors coding for the reporter genes lacZ or GFP readily transduced spiral ganglion cells. In addition, some transgene expression was detected in the stria vascularis after AAV-GFP injection. Gene expression persisted at least 8 weeks after viral vector injection. Present findings will help to develop future gene therapy protocols in the inner ear by using Ad and AAV coding for neurotrophins such as NT-3, BDNF, GDNF and VEGF.

摘要

外周性感音神经性听力损失是一种非常常见的内耳疾病,影响着近10%的人口。目前这种疾病无法治愈,但基因治疗已被认为是未来临床治疗的一种潜在有效方法。因此,我们研究了腺病毒(Ad)和腺相关病毒(AAV)载体转导豚鼠耳蜗的有效性。将其直接注射到耳蜗基底转后,我们发现编码报告基因lacZ或GFP的Ad和AAV载体都能轻易转导螺旋神经节细胞。此外,注射AAV-GFP后,在血管纹中检测到了一些转基因表达。病毒载体注射后基因表达至少持续8周。目前的研究结果将有助于通过使用编码神经营养因子如NT-3、BDNF、GDNF和VEGF的Ad和AAV来制定未来内耳基因治疗方案。

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