Abstract:
Sensorineural hearing loss is typically caused by damage to the cochlear hair cells (HCs) due to external stimuli or because of one\'s genetic factors and the inability to convert sound mechanical energy into nerve impulses. Adult mammalian cochlear HCs cannot regenerate spontaneously; therefore, this type of deafness is usually considered irreversible. Studies on the developmental mechanisms of HC differentiation have revealed that nonsensory cells in the cochlea acquire the ability to differentiate into HCs after the overexpression of specific genes, such as Atoh1, which makes HC regeneration possible. Gene therapy, through in vitro selection and editing of target genes, transforms exogenous gene fragments into target cells and alters the expression of genes in target cells to activate the corresponding differentiation developmental program in target cells. This review summarizes the genes that have been associated with the growth and development of cochlear HCs in recent years and provides an overview of gene therapy approaches in the field of HC regeneration. It concludes with a discussion of the limitations of the current therapeutic approaches to facilitate the early implementation of this therapy in a clinical setting.
摘要:
感觉神经性听力损失通常是由于外部刺激或遗传因素以及无法将声音机械能转化为神经冲动对耳蜗毛细胞(HCs)的损害引起的。成年哺乳动物耳蜗HC不能自发再生;因此,这种类型的耳聋通常被认为是不可逆转的。对HC分化发育机制的研究表明,耳蜗中的非感觉细胞在过表达特定基因后获得分化为HC的能力,例如Atoh1,这使得HC再生成为可能。基因治疗,通过体外选择和编辑靶基因,将外源基因片段转化到靶细胞中,并改变靶细胞中基因的表达,以激活靶细胞中相应的分化发育程序。本文综述了近年来与耳蜗HCs生长发育相关的基因,并对HC再生领域的基因治疗方法进行了综述。最后讨论了当前治疗方法的局限性,以促进该疗法在临床环境中的早期实施。