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Hyaluronic acid pretreatment for Sendai virus-mediated cochlear gene transfer

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 ro...

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Published in:Gene therapy 2016-02, Vol.23 (2), p.187-195
Main Authors: Kurioka, T, Mizutari, K, Niwa, K, Fukumori, T, Inoue, M, Hasegawa, M, Shiotani, A
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creator Kurioka, T
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description 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.
doi_str_mv 10.1038/gt.2015.94
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identifier ISSN: 0969-7128
ispartof Gene therapy, 2016-02, Vol.23 (2), p.187-195
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subjects 101/1
13/109
14/19
42/44
631/1647/2300/1514
692/699/375
82/51
Animals
Biomedical and Life Sciences
Biomedicine
Cell Biology
Cochlea
Cochlea - metabolism
Ear diseases
Expression vectors
Female
Gene Expression
Gene Therapy
Gene Transfer Techniques
Genetic Therapy - methods
Genetic transformation
Genetic Vectors
Genotoxicity
Green fluorescent protein
Guinea Pigs
Hearing loss
Hearing Loss, Sensorineural - therapy
Hearing protection
Human Genetics
Hyaluronic acid
Hyaluronic Acid - pharmacology
Methods
Nanotechnology
original-article
Properties
Reporter gene
Round Window, Ear - metabolism
Sendai virus
Sendai virus - genetics
Transfection - methods
Viruses
title Hyaluronic acid pretreatment for Sendai virus-mediated cochlear gene transfer
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