AAV8BP2 and AAV8 transduce the mammalian cochlear lateral wall and endolymphatic sac with high efficiency

Kevin Isgrig, Yasuko Ishibashi, Hyun Jae Lee, Jianliang Zhu, Mhamed Grati, Jean Bennett, Andrew J. Griffith, Isabelle Roux, Wade W. Chien

Research output: Contribution to journalArticlepeer-review

Abstract

Inner ear gene therapy using adeno-associated viruses (AAVs) has been successfully applied to several mouse models of hereditary hearing loss to improve their auditory function. While most inner ear gene therapy studies have focused on the mechanosensory hair cells and supporting cells in the organ of Corti, the cochlear lateral wall and the endolymphatic sac have not garnered much attention. The cochlear lateral wall and the endolymphatic sac play critical roles in inner ear ionic and fluid homeostasis. Mutations in genes expressed in the cochlear lateral wall and the endolymphatic sac are present in a large percentage of patients with hereditary hearing loss. In this study, we examine the transduction patterns and efficiencies of conventional (AAV2 and AAV8) and synthetic (AAV2.7m8, AAV8BP2, and Anc80L65) AAVs in the mouse inner ear. We found that AAV8BP2 and AAV8 are capable of transducing the marginal cells and intermediate cells in the stria vascularis. These two AAVs can also transduce the epithelial cells of the endolymphatic sac. Our data suggest that AAV8BP2 and AAV8 are highly useful viral vectors for gene therapy studies targeting the cochlear lateral wall and the endolymphatic sac.

Original languageEnglish (US)
Pages (from-to)371-383
Number of pages13
JournalMolecular Therapy - Methods and Clinical Development
Volume26
DOIs
StatePublished - Sep 8 2022

Keywords

  • cochlea
  • endolymphatic sac
  • gene therapy
  • hearing loss
  • inner ear
  • lateral wall
  • stria vascularis

ASJC Scopus subject areas

  • Genetics
  • Molecular Medicine
  • Molecular Biology

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