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György B, Meijer EJ, Ivanchenko MV, et al. 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. Mol Ther Methods Clin Dev. 2018;13:1-13doi: 10.1016/j.omtm.2018.11.003.
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. (2019). 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. Molecular therapy. Methods & clinical development, 131-13. https://doi.org/10.1016/j.omtm.2018.11.003
György, Bence, et al. "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." Molecular therapy. Methods & clinical development vol. 13 (2019): 1-13. doi: https://doi.org/10.1016/j.omtm.2018.11.003
György B, Meijer EJ, Ivanchenko MV, Tenneson K, Emond F, Hanlon KS, Indzhykulian AA, Volak A, Karavitaki KD, Tamvakologos PI, Vezina M, Berezovskii VK, Born RT, O'Brien M, Lafond JF, Arsenijevic Y, Kenna MA, Maguire CA, Corey DP. 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. Mol Ther Methods Clin Dev. 2018 Nov 20;13:1-13. doi: 10.1016/j.omtm.2018.11.003. eCollection 2019 Jun 14. PMID: 30581889; PMCID: PMC6297893.
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Mol Ther Methods Clin Dev. 2018 Nov 20;13:1-13. doi: 10.1016/j.omtm.2018.11.003. eCollection 2019 Jun 14.

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.

Molecular therapy. Methods & clinical development

Bence György, Elise J Meijer, Maryna V Ivanchenko, Kelly Tenneson, Frederick Emond, Killian S Hanlon, Artur A Indzhykulian, Adrienn Volak, K Domenica Karavitaki, Panos I Tamvakologos, Mark Vezina, Vladimir K Berezovskii, Richard T Born, Maureen O'Brien, Jean-François Lafond, Yvan Arsenijevic, Margaret A Kenna, Casey A Maguire, David P Corey

Affiliations

  1. Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
  2. Molecular Neurogenetics Unit, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02114, USA.
  3. Charles River Laboratories, Senneville, QC, Canada.
  4. Department of Otolaryngology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA 02114, USA.
  5. Charles River Laboratories, Frederick, MD 21701, USA.
  6. Unit of Retinal Degeneration and Regeneration, Department of Ophthalmology, University of Lausanne, Jules-Gonin Eye Hospital, Lausanne, Switzerland.
  7. Department of Otolaryngology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.

PMID: 30581889 PMCID: PMC6297893 DOI: 10.1016/j.omtm.2018.11.003

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

Keywords: AAV; adeno-associated virus vector; cochlea; gene delivery; hair cells; hereditary deafness; inner ear; non-human primate

References

  1. Hum Mol Genet. 2009 Aug 1;18(15):2748-60 - PubMed
  2. PLoS Genet. 2009 Aug;5(8):e1000607 - PubMed
  3. Mol Ther. 2012 May;20(5):960-71 - PubMed
  4. J Neurosci. 2012 Jul 11;32(28):9485-98 - PubMed
  5. Neuron. 2012 Jul 26;75(2):283-93 - PubMed
  6. Nature. 2014 Feb 20;506(7488):382-6 - PubMed
  7. Gene Ther. 2015 Feb;22(2):116-26 - PubMed
  8. J Neurosci. 2015 Apr 22;35(16):6366-80 - PubMed
  9. Sci Transl Med. 2015 Jul 8;7(295):295ra108 - PubMed
  10. Mol Ther. 2016 Feb;24(1):17-25 - PubMed
  11. Nat Biotechnol. 2016 Feb;34(2):204-9 - PubMed
  12. Mol Ther. 2017 Feb 1;25(2):379-391 - PubMed
  13. Nat Biotechnol. 2017 Mar;35(3):280-284 - PubMed
  14. Nat Biotechnol. 2017 Mar;35(3):264-272 - PubMed
  15. Sci Rep. 2017 Apr 03;7:45524 - PubMed
  16. J Assoc Res Otolaryngol. 2017 Aug;18(4):601-617 - PubMed
  17. Sci Rep. 2017 Oct 18;7(1):13480 - PubMed
  18. Hum Gene Ther. 2018 Apr;29(4):492-506 - PubMed
  19. Neurosci Lett. 2018 Feb 5;665:182-188 - PubMed
  20. Hum Mol Genet. 2018 Mar 1;27(5):761-779 - PubMed
  21. Mol Ther. 2018 Mar 7;26(3):664-668 - PubMed
  22. J Clin Invest. 2018 Aug 1;128(8):3382-3401 - PubMed
  23. Front Mol Neurosci. 2018 Jun 26;11:221 - PubMed
  24. J Virol. 1998 Mar;72(3):2224-32 - PubMed

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