期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 116, 期 10, 页码 4496-4501出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1817537116
关键词
dual AAV; gene therapy; otoferlin; deafness; DFNB9
资金
- Hearing Research Incorporation
- Fondation pour la Recherche Medicale
- Region Ile de France (DIM Therapie genique)
- European Union Seventh Framework Programme [HEALTH-F2-2010-242013]
- French government
- LabEx Lifesenses (Paribas Foundation) [ANR-10-BNP]
- LabEx Lifesenses (FAUN Stiftung)
- LabEx Lifesenses (LHW Stiftung)
- LabEx Lifesenses
Autosomal recessive genetic forms (DFNB) account for most cases of profound congenital deafness. Adeno-associated virus (AAV)-based gene therapy is a promising therapeutic option, but is limited by a potentially short therapeutic window and the constrained packaging capacity of the vector. We focus here on the otoferlin gene underlying DFNB9, one of the most frequent genetic forms of congenital deafness. We adopted a dual AAV approach using two different recombinant vectors, one containing the 5' and the other the 3' portions of otoferlin cDNA, which exceed the packaging capacity of the AAV when combined. A single delivery of the vector pair into the mature cochlea of Otof(-/-) mutant mice reconstituted the otoferlin cDNA coding sequence through recombination of the 5' and 3' cDNAs, leading to the durable restoration of otoferlin expression in transduced cells and a reversal of the deafness phenotype, raising hopes for future gene therapy trials in DFNB9 patients.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据