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Hyaluronic acid pretreatment for Sendai virus-mediated cochlear gene transfer

Gene Therapy volume 23, pages 187–195 (2016)Cite this article

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Abstract

Gene therapy with viral vectors is one of the most promising strategies for sensorineural hearing loss. However, safe and effective administration of the viral vector into cochlear tissue is difficult because of the anatomical isolation of the cochlea. We investigated the efficiency and safety of round window membrane (RWM) application of Sendai virus, one of the most promising non-genotoxic vectors, after pretreatment with hyaluronic acid (HA) on the RWM to promote efficient viral translocation into the cochlea. Sendai virus expressing the green fluorescent protein reporter gene was detected throughout cochlear tissues following application combined with HA pretreatment. Quantitative analysis revealed that maximum expression was reached 3 days after treatment. The efficiency of transgene expression was several 100-fold greater with HA pretreatment than that without. Furthermore, unlike the conventional intracochlear delivery methods, this approach did not cause hearing loss. These findings reveal the potential utility of gene therapy with Sendai virus and HA for treatment of sensorineural hearing loss.

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Acknowledgements

This work was supported by JSPS KAKENHI Grant Number 26462572 (for KM).

Author contributions

TK and KM designed the experiments. TK, KM, KN, TF, MI, MH and AS performed research and analyzed the data. TK and KM co-wrote the manuscript. All authors discussed the results and commented on the manuscript.

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Authors and Affiliations

  1. Department of Otolaryngology, Head and Neck Surgery, National Defense Medical College, Saitama, Japan

    T Kurioka, K Mizutari, K Niwa, T Fukumori & A Shiotani

  2. DNAVEC Corporation, Ibaraki, Japan

    M Inoue & M Hasegawa

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  1. T Kurioka
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  2. K Mizutari
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Correspondence to K Mizutari.

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Kurioka, T., Mizutari, K., Niwa, K. et al. Hyaluronic acid pretreatment for Sendai virus-mediated cochlear gene transfer. Gene Ther 23, 187–195 (2016). https://doi.org/10.1038/gt.2015.94

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