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. 2025 Sep 3;33(9):4290-4302.
doi: 10.1016/j.ymthe.2025.05.022. Epub 2025 May 28.

Delivery of AAV vectors to the superior olivary complex enables efficient adult cochlear transduction via axonal transport

Jerusha Naidoo  1 , Yin Ren  2 , Matthew Rocco  3 , Eric Bielefeld  4 , Allison O'Brien  3 , Hsuan-Chih Kuo  2 , Nathan McFarland  3 , Matthew Avenarius  5 , Manpreet Takhar  3 , Geneva Frank  3 , Victor Van Laar  3 , Krystof Bankiewicz  3
Affiliations

Delivery of AAV vectors to the superior olivary complex enables efficient adult cochlear transduction via axonal transport

Jerusha Naidoo et al. Mol Ther. .

Abstract

Significant breakthroughs have been made in translation of adeno-associated virus (AAV) vectors for hearing disorders targeting auditory hair cells (HCs). In addition to HCs, spiral ganglion neurons (SGNs) are also impacted in a large number of sensorineural hearing loss cases in adults. However when administered directly into the cochlea in rodents aged older than P1-P3, AAV-mediated SGN transduction efficiency decreases dramatically. An efficient gene-delivery method to transduce adult SGNs is needed. Our group has a track record of utilizing axonal transport to transduce brain structures distal from the site of AAV injection. We investigated whether SGNs could be transduced in adult rats following intraparenchymal AAV administration to the olivary complex. Cochlear transduction was observed with the following common AAV serotypes expressing green fluorescent protein: AAV6, AAV9, AAV-Anc80, and AAV-PhP.B. Cochlear transduction was observed with all serotypes, but the cellular tropism and efficiency of gene transfer varied across the cochlear spiral (apex, middle, base) with different AAV serotypes, with some transducing both SGNs and HCs, while others transduced SGNs or HCs exclusively. This study provides proof of concept that AAV delivery to the olivary complex can efficiently deliver transgenes to SGNs in the adult mammalian cochlea.

Keywords: AAV; adeno-associated virus; auditory nerve; cochlea; cochlea nucleus; gene therapy; hair cells; hearing; olivary complex; spiral ganglion neurons.

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Conflict of interest statement

Declaration of interests J.N., Y.R., and K.B are inventors on a patent application by OSU pertaining to the method described in this manuscript. Patent application: #PCT/US2024/010999 (as yet unpublished).

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