Blanc Fabian, Mondain Michel, Bemelmans Alexis-Pierre, Affortit Corentin, Puel Jean-Luc, Wang Jing
INSERM - UMR 1051, Institut des Neurosciences de Montpellier, Hôpital Saint Eloi - Bâtiment INM, 80, rue Augustin Fliche - BP 74103, 34091 Montpellier, France.
Université de Montpellier, 163 rue Auguste Broussonnet, 34090 Montpellier, France.
J Clin Med. 2020 Feb 21;9(2):589. doi: 10.3390/jcm9020589.
Over the last decade, pioneering molecular gene therapy for inner-ear disorders have achieved experimental hearing improvements after a single local or systemic injection of adeno-associated, virus-derived vectors (rAAV for recombinant AAV) encoding an extra copy of a normal gene, or ribozymes used to modify a genome. These results hold promise for treating congenital or later-onset hearing loss resulting from monogenic disorders with gene therapy approaches in patients. In this review, we summarize the current state of rAAV-mediated inner-ear gene therapies including the choice of vectors and delivery routes, and discuss the prospects and obstacles for the future development of efficient clinical rAAV-mediated cochlear gene medicine therapy.
在过去十年中,针对内耳疾病的开创性分子基因疗法在单次局部或全身注射编码正常基因额外拷贝的腺相关病毒衍生载体(重组腺相关病毒,即rAAV)或用于修饰基因组的核酶后,已实现了实验性听力改善。这些结果为采用基因治疗方法治疗由单基因疾病导致的先天性或迟发性听力损失的患者带来了希望。在本综述中,我们总结了rAAV介导的内耳基因治疗的现状,包括载体和给药途径的选择,并讨论了高效临床rAAV介导的耳蜗基因药物治疗未来发展的前景和障碍。