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Choice of vector and surgical approach enables efficient cochlear gene transfer in nonhuman primate

Author

Listed:
  • Eva Andres-Mateos

    (Schepens Eye Research Institute and Massachusetts Eye and Ear
    Harvard Medical School
    Akouos Inc.)

  • Lukas D. Landegger

    (Eaton Peabody Laboratories, Massachusetts Eye and Ear
    Massachusetts Eye and Ear and Harvard Medical School
    Vienna General Hospital and Medical University of Vienna)

  • Carmen Unzu

    (Schepens Eye Research Institute and Massachusetts Eye and Ear
    Harvard Medical School)

  • Jean Phillips

    (Massachusetts Eye and Ear and Harvard Medical School)

  • Brian M. Lin

    (Massachusetts Eye and Ear and Harvard Medical School)

  • Nicholas A. Dewyer

    (Massachusetts Eye and Ear and Harvard Medical School)

  • Julio Sanmiguel

    (Schepens Eye Research Institute and Massachusetts Eye and Ear
    Harvard Medical School)

  • Fotini Nicolaou

    (Schepens Eye Research Institute and Massachusetts Eye and Ear
    Harvard Medical School)

  • Michelle D. Valero

    (Eaton Peabody Laboratories, Massachusetts Eye and Ear
    Massachusetts Eye and Ear and Harvard Medical School)

  • Kathrin I. Bourdeu

    (Massachusetts Eye and Ear, Harvard Medical School)

  • William F. Sewell

    (Eaton Peabody Laboratories, Massachusetts Eye and Ear
    Massachusetts Eye and Ear and Harvard Medical School)

  • Rudolph J. Beiler

    (Boston University)

  • Michael J. McKenna

    (Eaton Peabody Laboratories, Massachusetts Eye and Ear
    Massachusetts Eye and Ear and Harvard Medical School
    Otopathology Laboratory, Massachusetts Eye and Ear
    Harvard University)

  • Konstantina M. Stankovic

    (Eaton Peabody Laboratories, Massachusetts Eye and Ear
    Massachusetts Eye and Ear and Harvard Medical School
    Harvard University
    Harvard University)

  • Luk H. Vandenberghe

    (Schepens Eye Research Institute and Massachusetts Eye and Ear
    Harvard Medical School
    Harvard University
    The Broad Institute of Harvard and MIT)

Abstract

Inner ear gene therapy using adeno-associated viral vectors (AAV) promises to alleviate hearing and balance disorders. We previously established the benefits of Anc80L65 in targeting inner and outer hair cells in newborn mice. To accelerate translation to humans, we now report the feasibility and efficiency of the surgical approach and vector delivery in a nonhuman primate model. Five rhesus macaques were injected with AAV1 or Anc80L65 expressing eGFP using a transmastoid posterior tympanotomy approach to access the round window membrane after making a small fenestra in the oval window. The procedure was well tolerated. All but one animal showed cochlear eGFP expression 7–14 days following injection. Anc80L65 in 2 animals transduced up to 90% of apical inner hair cells; AAV1 was markedly less efficient at equal dose. Transduction for both vectors declined from apex to base. These data motivate future translational studies to evaluate gene therapy for human hearing disorders.

Suggested Citation

  • Eva Andres-Mateos & Lukas D. Landegger & Carmen Unzu & Jean Phillips & Brian M. Lin & Nicholas A. Dewyer & Julio Sanmiguel & Fotini Nicolaou & Michelle D. Valero & Kathrin I. Bourdeu & William F. Sewe, 2022. "Choice of vector and surgical approach enables efficient cochlear gene transfer in nonhuman primate," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28969-3
    DOI: 10.1038/s41467-022-28969-3
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    References listed on IDEAS

    as
    1. Kevin Isgrig & Devin S. McDougald & Jianliang Zhu & Hong Jun Wang & Jean Bennett & Wade W. Chien, 2019. "AAV2.7m8 is a powerful viral vector for inner ear gene therapy," Nature Communications, Nature, vol. 10(1), pages 1-8, December.
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