In vitro and in vivo suppression of GJB2 expression by RNA interference

Yukihide Maeda, Kunihiro Fukushima, Kazunori Nishizaki, Richard J H Smith

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77 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1641-1650
Number of pages10
JournalHuman Molecular Genetics
Issue number12
Publication statusPublished - Jun 15 2005


ASJC Scopus subject areas

  • Genetics

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