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A modified adenovirus can transfect cochlear hair cells in vivo without compromising cochlear function

Gene Therapy volume 8, pages 789–794 (2001)Cite this article

Abstract

The loss of cochlear hair cells, or the loss of their capacity to transduce acoustic signals, is believed to be the underlying mechanism in many forms of hearing loss. To develop viral vectors that allow for the introduction of genes directly into the cochleae of adult animals, replication-deficient (E1−, E3−) and replication-defective (E1−, E3−, pol−) adenovirus vectors were used to transduce the bacterial β-galactosidase gene into the hair cells of the guinea pig cochlea in vivo. Distortion product otoacoustic emissions, which monitor the functional status of outer hair cells, were measured throughout the viral infection periods to identify hair cell ototoxicity. The results demonstrated that the use of the (E1−, E3−) adenovirus vectors containing CMV-driven LacZ, compromised cochlear function when gradually introduced into scala tympani via an osmotic pump. However, when (E1−, E3−, pol−) adenoviral vectors containing CMV-driven LacZ were used to transduce cochlear hair cells, there was no loss of cochlear function over the frequency regions tested, and β-galactosidase (β-gal) was detected in over 80% of all hair cells. Development of a viral vector that infects cochlear hair cells without virus-induced ototoxic effects is crucial for gene replacement strategies to treat certain forms of inherited deafness and for otoprotective strategies to prevent hair cell losses to treat progressive hearing disorders. Moreover, in vivo (E1−, E3−, pol−) adenovirus mediated gene-transfer techniques applied to adult guinea pig cochleae may be useful in testing several hypotheses concerning what roles specific genes play in normal cochlear function.

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Acknowledgements

This work was supported by grants from the Public Health Service DC03086 (AEL), DK52925 (AA), Muscular Dystrophy Association, USA (AA), and funds from the University of Miami's Stanley Glaser Research Foundation and Chandler Chair (AEL). We would like to thank Dr Ken Muller for his assistance with plastic sectioning.

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Authors and Affiliations

  1. Department of Otolaryngology, University of Miami School of Medicine, Miami, FL, USA

    A E Luebke & J D Steiger

  2. Neuroscience Program, University of Miami School of Medicine, Miami, FL, USA

    A E Luebke

  3. Department of Pediatrics, Division of Medical Genetics and Department of Genetics, Duke University Medical Center, Durham, NC, USA

    B L Hodges & A Amalfitano

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  1. A E Luebke
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  2. J D Steiger
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  3. B L Hodges
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  4. A Amalfitano
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Luebke, A., Steiger, J., Hodges, B. et al. A modified adenovirus can transfect cochlear hair cells in vivo without compromising cochlear function. Gene Ther 8, 789–794 (2001). https://doi.org/10.1038/sj.gt.3301445

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