Therapeutic regulation of gene expression in the inner ear using RNA interference

Yukihide Maeda, Abraham M. Sheffield, Richard J.H. Smith

Research output: Chapter in Book/Report/Conference proceedingChapter

32 Citations (Scopus)


Targeting and downregulating specific genes with antisense and decoy oligonucleotides, ribozymes or RNA interference (RNAi) offer the theoretical potential of altering a disease phenotype. Here we review the molecular mechanism behind the in vivo application of RNAi-mediated gene silencing, focusing on its application to the inner ear. RNAi is a physiological phenomenon in which small, double-stranded RNA molecules (small interfering RNA, siRNA) reduce expression of homologous genes. Notable for its exquisite sequence specificity, it is ideally applied to diseases caused by a gain-of-function mechanism of action. Types of deafness in which gain-of-function mutations are observed include DFNA2 (KCNQ4), DFNA3 (GJB2) and DFNA5 (DFNA5). Several strategies can be used to deliver siRNA into the inner ear, including cationic liposomes, adeno-associated and lentiviral vectors, and adenoviral vectors. Transduction efficiency with cationic liposomes is low and the effect is transient; with adeno-associated and lentiviral vectors, long-term transfection is possible using a small hairpin RNA expression cassette.

Original languageEnglish
Title of host publicationGene Therapy of Cochlear Deafness
Subtitle of host publicationPresent Concepts and Future Aspects
EditorsAllen Ryan
Number of pages24
Publication statusPublished - 2009
Externally publishedYes

Publication series

NameAdvances in Oto-Rhino-Laryngology
ISSN (Print)0065-3071

ASJC Scopus subject areas

  • Otorhinolaryngology


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