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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 |
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creator | Kurioka, T Mizutari, K Niwa, K Fukumori, T Inoue, M Hasegawa, M Shiotani, A |
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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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.</description><subject>101/1</subject><subject>13/109</subject><subject>14/19</subject><subject>42/44</subject><subject>631/1647/2300/1514</subject><subject>692/699/375</subject><subject>82/51</subject><subject>Animals</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cell Biology</subject><subject>Cochlea</subject><subject>Cochlea - metabolism</subject><subject>Ear diseases</subject><subject>Expression vectors</subject><subject>Female</subject><subject>Gene Expression</subject><subject>Gene Therapy</subject><subject>Gene Transfer Techniques</subject><subject>Genetic Therapy - methods</subject><subject>Genetic transformation</subject><subject>Genetic Vectors</subject><subject>Genotoxicity</subject><subject>Green fluorescent protein</subject><subject>Guinea Pigs</subject><subject>Hearing loss</subject><subject>Hearing Loss, Sensorineural - 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Academic</collection><collection>Biotechnology Research Abstracts</collection><jtitle>Gene therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kurioka, T</au><au>Mizutari, K</au><au>Niwa, K</au><au>Fukumori, T</au><au>Inoue, M</au><au>Hasegawa, M</au><au>Shiotani, A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hyaluronic acid pretreatment for Sendai virus-mediated cochlear gene transfer</atitle><jtitle>Gene therapy</jtitle><stitle>Gene Ther</stitle><addtitle>Gene Ther</addtitle><date>2016-02-01</date><risdate>2016</risdate><volume>23</volume><issue>2</issue><spage>187</spage><epage>195</epage><pages>187-195</pages><issn>0969-7128</issn><eissn>1476-5462</eissn><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. 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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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