A model of gene therapy for autosomal dominant hearing impairment: the application of RNA interference for the treatment of hearing impairment
| Project/Area Number |
17390460
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Otorhinolaryngology
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| Research Institution | Okayama University |
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Principal Investigator |
FUKUSHIMA Kunihiro Okayama University Hospital of Medical and Dentistry, Lecturers, 医学部・歯学部附属病院, 講師 (50284112)
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| Co-Investigator(Kenkyū-buntansha) |
MAEDA Yukihide Okayama University Hospital of Medical and Dentistry, Medical staff, 医学部・歯学部附属病院, 医員 (00423327)
加藤 英政 東北大学, 先進医工学研究機構, 助教授 (50292123)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥5,600,000 (Direct Cost: ¥5,600,000)
Fiscal Year 2006: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2005: ¥2,900,000 (Direct Cost: ¥2,900,000)
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| Keywords | RNA interference / siRNA / GJB2 / hearing impairment / deafness / gene therapy / Autosomal dominant / cochlea / dominant negative効果 / 感音難聴 / 内耳 / 治療効果 / ABR |
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| Research Abstract |
Mutations in GJB2 (gap junction protein, beta-2) are the major cause of autosomal recessive non-syndromic hearing loss. A few allele variants of this gene also cause autosomal dominant non-syndromic hearing loss as a dominant-negative consequence of expression of the mutant protein. Allele-specific gene suppression by RNA interference (RNAi) is a potentially attractive strategy to prevent hearing loss caused by this mechanism. In this proof-of-principle study, we identified a potent GJB2-targeting short interfering RNA (siRNA) to post-transcriptionally silence the expression of the R75W allele variant of GJB2 in cultured mammalian cells. In a mouse model, this siRNA duplex selectively suppressed GJB2R75W expression by >70% of control levels, thereby preventing hearing loss. The level of endogenous murine Gjb2 expression was not affected. Our data show that RNAi can be used with specificity and efficiency in vivo to protect against hearing loss caused as a dominant-negative consequence of mutant gene expression.
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Report
(3 results)
Research Products
(13 results)
