Cochlear gene therapy
Cochlear gene therapy
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DOI：
10.1097/01.aud.0000079798.24346.35
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发表时间：
2003-08-01
期刊：
影响因子：
3.7
通讯作者：
Mhatre, AN
中科院分区：
文献类型：
--
作者：
Lalwani, AK;Mhatre, AN
尽管听力障碍在人类中普遍存在，但治疗选择仅限于使用放大器或植入式电子假体进行康复。与处方眼镜恢复正常视力的能力相反，如果没有一段时间的学习和适应，感音神经性耳聋的现有疗法不能恢复完美的听力。助听器和人工耳蜗都能在困难的情况下做到最好，但并不是万能的。基因转移作为一种治疗方法受到了极大的关注，因为它提供了阻止、逆转或治愈遗传性和非遗传性耳聋的希望。与传统治疗相比，基因治疗方法提供了使用正常生理听力装置恢复听力的潜在优势，并使更广泛的患者受益。本章描述了沿着发展基因疗法治疗耳聋的道路上的第一个实验步骤，以及如果这种方法要取得成功必须克服的一些障碍。耳蜗中的基因转移研究不仅限于设计治疗策略以减轻听觉功能障碍，而且还有助于听力的分子遗传分析。在实验上，将基因引入内耳的能力可以导致耳蜗蛋白质功能的阐明和内耳特异性基因的控制。在治疗上，在突发性耳聋或进行性听力损失的情况下，由基因治疗载体介导的营养因子的迅速递送可以减少随后的组织损伤并保护听力。在这一期专门讨论耳聋遗传学的《耳与听力》杂志中，遗传性听力障碍基因的功能障碍与听力损失有关，是基因治疗的潜在靶点。在设计耳蜗基因治疗中，关于病毒载体的选择、递送途径和安全性考虑的几个问题是至关重要的，并在下面进行综述。
Despite the prevalence of hearing disorders in humans, therapeutic options are limited to rehabilitation with amplification or implantable electronic prosthesis. In contrast to prescription glasses’ ability to restore normal vision, and that without a period of learning and adaptation, available therapeutics for sensorineural deafness do not restore perfect hearing. Both hearing aids and cochlear implants make the best of a difficult situation but are not a panacea. Gene transfer as a form of therapeutics has received significant attention as it offers the hope of arresting, reversing or curing deafness of genetic and non-genetic origin. In contrast to conventional treatment, the gene therapy approach offers the potential advantage of restoring hearing using normal physiologic hearing apparatus and benefiting a wider range of patients. This chapter describes the first experimental steps along the path of developing gene therapy to cure deafness, and some of the obstacles that must be overcome if this approach is to succeed. Gene transfer studies in the cochlea are not limited to designing therapeutic strategies to alleviate auditory dysfunction, but can also contribute towards molecular genetic analysis of hearing. Experimentally, the ability to introduce genes into the inner ear can lead to the elucidation of the function of cochlear proteins and control of inner ear specific genes. Therapeutically, the prompt delivery of trophic factors in cases of sudden deafness or progressive hearing loss, mediated by gene therapy vectors, could reduce the consequent tissue damage and preserve hearing. In this issue of Ear and Hearing devoted to Genetics of Deafness, the hereditary hearing impairment genes whose dysfunction is associated with hearing loss, represent potential targets for gene therapy. In designing cochlear gene therapy, several issues regarding the choice of viral vector, the route of delivery, and safety consideration are critical and are reviewed below.