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Rescue of Hearing by Gene Delivery to Inner-Ear Hair Cells Using Exosome-Associated AAV.
György, Bence; Sage, Cyrille; Indzhykulian, Artur A; Scheffer, Deborah I; Brisson, Alain R; Tan, Sisareuth; Wu, Xudong; Volak, Adrienn; Mu, Dakai; Tamvakologos, Panos I; Li, Yaqiao; Fitzpatrick, Zachary; Ericsson, Maria; Breakefield, Xandra O; Corey, David P; Maguire, Casey A.
Affiliation
  • György B; Department of Neurobiology and Howard Hughes Medical Institute, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA; Department of Neurology, Massachusetts General Hospital and NeuroDiscovery Center, Harvard Medical School, Building 149, Charlestown, Boston, MA 02129, USA.
  • Sage C; Department of Neurobiology and Howard Hughes Medical Institute, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA.
  • Indzhykulian AA; Department of Neurobiology and Howard Hughes Medical Institute, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA.
  • Scheffer DI; Department of Neurobiology and Howard Hughes Medical Institute, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA.
  • Brisson AR; Molecular Imaging and NanoBioTechnology, UMR-5248-CBMN CNRS-University of Bordeaux-IPB, Allée Geoffroy Saint-Hilaire, F-33600 Pessac, France.
  • Tan S; Molecular Imaging and NanoBioTechnology, UMR-5248-CBMN CNRS-University of Bordeaux-IPB, Allée Geoffroy Saint-Hilaire, F-33600 Pessac, France.
  • Wu X; Department of Neurobiology and Howard Hughes Medical Institute, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA.
  • Volak A; Department of Neurology, Massachusetts General Hospital and NeuroDiscovery Center, Harvard Medical School, Building 149, Charlestown, Boston, MA 02129, USA.
  • Mu D; Department of Neurology, Massachusetts General Hospital and NeuroDiscovery Center, Harvard Medical School, Building 149, Charlestown, Boston, MA 02129, USA.
  • Tamvakologos PI; Department of Neurobiology and Howard Hughes Medical Institute, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA.
  • Li Y; Department of Neurobiology and Howard Hughes Medical Institute, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA.
  • Fitzpatrick Z; Department of Neurology, Massachusetts General Hospital and NeuroDiscovery Center, Harvard Medical School, Building 149, Charlestown, Boston, MA 02129, USA.
  • Ericsson M; Department of Cell Biology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA.
  • Breakefield XO; Department of Neurology, Massachusetts General Hospital and NeuroDiscovery Center, Harvard Medical School, Building 149, Charlestown, Boston, MA 02129, USA; Program in Neuroscience, Harvard Medical School, Building 149, Charlestown, Boston, MA 02129, USA.
  • Corey DP; Department of Neurobiology and Howard Hughes Medical Institute, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA. Electronic address: dcorey@hms.harvard.edu.
  • Maguire CA; Department of Neurology, Massachusetts General Hospital and NeuroDiscovery Center, Harvard Medical School, Building 149, Charlestown, Boston, MA 02129, USA. Electronic address: cmaguire@mgh.harvard.edu.
Mol Ther ; 25(2): 379-391, 2017 02 01.
Article in En | MEDLINE | ID: mdl-28082074
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. Exo-AAV1-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/Tmhs-/-]). Exo-AAV is a powerful gene delivery system for hair cell research and may be useful for gene therapy for deafness.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Gene Transfer Techniques / Dependovirus / Exosomes / Genetic Vectors / Hair Cells, Auditory, Inner / Hearing Type of study: Risk_factors_studies Limits: Animals Language: En Journal: Mol Ther Journal subject: BIOLOGIA MOLECULAR / TERAPEUTICA Year: 2017 Type: Article Affiliation country: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Gene Transfer Techniques / Dependovirus / Exosomes / Genetic Vectors / Hair Cells, Auditory, Inner / Hearing Type of study: Risk_factors_studies Limits: Animals Language: En Journal: Mol Ther Journal subject: BIOLOGIA MOLECULAR / TERAPEUTICA Year: 2017 Type: Article Affiliation country: United States