AAV-S: A versatile capsid variant for transduction of mouse and primate inner ear.

Autor:	Ivanchenko MV; Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA., Hanlon KS; Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA.; Molecular Neurogenetics Unit, Massachusetts General Hospital, 13 Street, Charlestown, MA 02114, USA., Hathaway DM; Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA., Klein AJ; Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA., Peters CW; Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA., Li Y; Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA., Tamvakologos PI; Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA., Nammour J; Molecular Neurogenetics Unit, Massachusetts General Hospital, 13 Street, Charlestown, MA 02114, USA., Maguire CA; Molecular Neurogenetics Unit, Massachusetts General Hospital, 13 Street, Charlestown, MA 02114, USA.; Department of Neurology, Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA., Corey DP; Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA.
Jazyk:	angličtina
Zdroj:	Molecular therapy. Methods & clinical development [Mol Ther Methods Clin Dev] 2021 Mar 29; Vol. 21, pp. 382-398. Date of Electronic Publication: 2021 Mar 29 (Print Publication: 2021).
DOI:	10.1016/j.omtm.2021.03.019
Abstrakt:	Gene therapy strategies using adeno-associated virus (AAV) vectors to treat hereditary deafnesses have shown remarkable efficacy in some mouse models of hearing loss. Even so, there are few AAV capsids that transduce both inner and outer hair cells-the cells that express most deafness genes-and fewer still shown to transduce hair cells efficiently in primates. AAV capsids with robust transduction of inner and outer hair cells in primate cochlea will be needed for most clinical trials. Here, we test a capsid that we previously isolated from a random capsid library, AAV-S, for transduction in mouse and non-human primate inner ear. In both mice and cynomolgus macaques, AAV-S mediates highly efficient reporter gene expression in a variety of cochlear cells, including inner and outer hair cells, fibrocytes, and supporting cells. In a mouse model of Usher syndrome type 3A, AAV-S encoding CLRN1 robustly and durably rescues hearing. Overall, our data indicate that AAV-S is a promising candidate for therapeutic gene delivery to the human inner ear. Competing Interests: The authors declare the following competing interests: C.A.M. has financial interests in Chameleon Biosciences, Inc. and Sphere Gene Therapeutics, companies developing enveloped adeno-associated virus vector platform technologies. C.A.M. also has a financial interest in Claritas Bio, a company developing gene therapies to treat hearing disorders. C.A.M.’s interests were reviewed and are managed by the Massachusetts General Hospital and Partners HealthCare in accordance with their conflict of interest policies. D.P.C. has a financial interest in Claritas Bio. C.A.M., K.S.H., D.P.C., and M.V.I. have filed patent applications involving the AAV-S capsid for gene delivery and therapy applications. (© 2021 The Author(s).)
Databáze:	MEDLINE
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