Gene Transfer with AAV9-PHP.B Rescues Hearing in a Mouse Model of Usher Syndrome 3A and Transduces Hair Cells in a Non-human Primate.

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State: Serval
Version: Final published version
License: CC BY-NC-ND 4.0
Serval ID
serval:BIB_867BE52AD282
Type
Article: article from journal or magazin.
Collection
Publications
Title
Gene Transfer with AAV9-PHP.B Rescues Hearing in a Mouse Model of Usher Syndrome 3A and Transduces Hair Cells in a Non-human Primate.
Journal
Molecular therapy. Methods & clinical development
Author(s)
György B., Meijer E.J., Ivanchenko M.V., Tenneson K., Emond F., Hanlon K.S., Indzhykulian A.A., Volak A., Karavitaki K.D., Tamvakologos P.I., Vezina M., Berezovskii V.K., Born R.T., O'Brien M., Lafond J.F., Arsenijevic Y., Kenna M.A., Maguire C.A., Corey D.P.
ISSN
2329-0501 (Print)
ISSN-L
2329-0501
Publication state
Published
Issued date
14/06/2019
Peer-reviewed
Oui
Volume
13
Pages
1-13
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
Hereditary hearing loss often results from mutation of genes expressed by cochlear hair cells. Gene addition using AAV vectors has shown some efficacy in mouse models, but clinical application requires two additional advances. First, new AAV capsids must mediate efficient transgene expression in both inner and outer hair cells of the cochlea. Second, to have the best chance of clinical translation, these new vectors must also transduce hair cells in non-human primates. Here, we show that an AAV9 capsid variant, PHP.B, produces efficient transgene expression of a GFP reporter in both inner and outer hair cells of neonatal mice. We show also that AAV9-PHP.B mediates almost complete transduction of inner and outer HCs in a non-human primate. In a mouse model of Usher syndrome type 3A deafness (gene <i>CLRN1</i> ), we use AAV9-PHP.B encoding <i>Clrn1</i> to partially rescue hearing. Thus, we have identified a vector with promise for clinical treatment of hereditary hearing disorders, and we demonstrate, for the first time, viral transduction of the inner ear of a primate with an AAV vector.
Keywords
AAV, adeno-associated virus vector, cochlea, gene delivery, hair cells, hereditary deafness, inner ear, non-human primate
Pubmed
Open Access
Yes
Create date
20/01/2019 17:04
Last modification date
29/05/2019 7:09
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