Rescue of Hearing by Gene Delivery to Inner-Ear Hair Cells Using Exosome-Associated AAV

被引：201

作者：

Gyorgy, Bence ^{[1
,2
,3
,4
]}

Sage, Cyrille ^{[1
,2
]}

Indzhykulian, Artur A. ^{[1
,2
]}

Scheffer, Deborah I. ^{[1
,2
]}

Brisson, Alain R. ^{[5
]}

Tan, Sisareuth ^{[5
]}

Wu, Xudong ^{[1
,2
]}

Volak, Adrienn ^{[3
,4
]}

Mu, Dakai ^{[3
,4
]}

Tamvakologos, Panos I. ^{[1
,2
]}

Li, Yaqiao ^{[1
,2
]}

Fitzpatrick, Zachary ^{[3
,4
]}

Ericsson, Maria ^{[6
]}

Breakefield, Xandra O. ^{[3
,4
,7
]}

Corey, David P. ^{[1
,2
]}

Maguire, Casey A. ^{[3
,4
]}

机构：

[1] Harvard Med Sch, Dept Neurobiol, 220 Longwood Ave, Boston, MA 02115 USA

[2] Harvard Med Sch, Howard Hughes Med Inst, 220 Longwood Ave, Boston, MA 02115 USA

[3] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Bldg 149, Charlestown, MA 02129 USA

[4] Harvard Med Sch, NeuroDiscovery Ctr, Bldg 149, Charlestown, MA 02129 USA

[5] Univ Bordeaux, IPB, CNRS, Mol Imaging & NanoBioTechnol,UMR 5248,CBMN, Allee Geoffroy St Hilaire, F-33600 Pessac, France

[6] Harvard Med Sch, Dept Cell Biol, 220 Longwood Ave, Boston, MA 02115 USA

[7] Harvard Med Sch, Program Neurosci, Bldg 149, Charlestown, MA 02129 USA

来源：

MOLECULAR THERAPY | 2017年 / 25卷 / 02期

关键词：

ADENOASSOCIATED VIRUS VECTORS; EFFICIENT TRANSDUCTION; EXTRACELLULAR VESICLES; THERAPY; DEAFNESS; ROBUST; TMHS;

D O I：

10.1016/j.ymthe.2016.12.010

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 [微生物学]; 090105 [作物生产系统与生态工程];

摘要：

Adeno-associated virus (AAV) is a safe and effective vector for gene therapy for retinal disorders. Gene therapy for hearing disorders is not as advanced, in part because gene delivery to sensory hair cells of the inner ear is inefficient. Although AAV transduces the inner hair cells of the mouse cochlea, outer hair cells remain refractory to transduction. Here, we demonstrate that a vector, exosome-associated AAV (exo-AAV), is a potent carrier of transgenes to all inner ear hair cells. ExoAAV1-GFP is more efficient than conventional AAV1-GFP, both in mouse cochlear explants in vitro and with direct cochlear injection in vivo. Exo-AAV shows no toxicity in vivo, as assayed by tests of auditory and vestibular function. Finally, exo-AAV1 gene therapy partially rescues hearing in a mouse model of hereditary deafness (lipoma HMGIC fusion partner-like 5/ tetraspan membrane protein of hair cell stereocilia [Lhfpl5/ Tmh(-/-)]). Exo-AAV is a powerful gene delivery system for hair cell research and may be useful for gene therapy for deafness.

引用

页码：379 / 391

页数：13

共 28 条

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Restoration of Hearing in the VGLUT3 Knockout Mouse Using Virally Mediated Gene Therapy [J].