1. ¹Division of Genetic Therapeutics, Center for Molecular Medicine, Jichi Medical School, 3311-1 Yakushiji, Minami-kawachi, Kawachi, Tochigi 329-0498, Japan
2. ²Department of Otolaryngology and Head and Neck Surgery, Jichi Medical School, 3311-1 Yakushiji, Minami-kawachi, Kawachi, Tochigi 329-0498, Japan
3. ³Department of Neurobiology, Northeastern Ohio Universities College of Medicine, Rootstown, OH 44272, USA
4. ⁴Department of Physiology, Jichi Medical School, 3311-1 Yakushiji, Minami-kawachi, Kawachi, Tochigi 329-0498, Japan
5. ⁵Department of Medicine, Division of Neurology, Jichi Medical School, 3311-1 Yakushiji, Minami-kawachi, Kawachi, Tochigi 329-0498, Japan
6. ⁶Department of Otolaryngology and Head and Neck Surgery, Faculty of Medicine, University of the Ryukyus, Okinawa 903-0213, Japan
7. ⁷Department of Anatomy, Jichi Medical School, 3311-1 Yakushiji, Minami-kawachi, Kawachi, Tochigi 329-0498, Japan

Correspondence: Keiya Ozawa, Fax: (+81) 285 44 8675. E-mail: kozawa@jichi.ac.jp

Received 1 November 2004; Accepted 24 March 2005.

Abstract

Recombinant adeno-associated virus (AAV) vectors are of interest for cochlear gene therapy because of their ability to mediate the efficient transfer and long-term stable expression of therapeutic genes in a wide variety of postmitotic tissues with minimal vector-related cytotoxicity. In the present study, seven AAV serotypes (AAV1–5, 7, 8) were used to construct vectors. The expression of EGFP by the chicken -actin promoter associated with the cytomegalovirus immediate-early enhancer in cochlear cells showed that each of these serotypes successfully targets distinct cochlear cell types. In contrast to the other serotypes, the AAV3 vector specifically transduced cochlear inner hair cells with high efficiency in vivo, while the AAV1, 2, 5, 7, and 8 vectors also transduced these and other cell types, including spiral ganglion and spiral ligament cells. There was no loss of cochlear function with respect to evoked auditory brain-stem responses over the range of frequencies tested after the injection of AAV vectors. These findings are of value for further molecular studies of cochlear inner hair cells and for gene replacement strategies to correct recessive genetic hearing loss due to monogenic mutations in these cells.