Book chapter
Therapeutic Regulation of Gene Expression in the Inner Ear using RNA Interference
Gene Therapy of Cochlear Deafness, pp.13-36
Advances in Oto-Rhino-Laryngology, S. Karger AG
05/2009
DOI: 10.1159/000218205
PMCID: PMC2867253
PMID: 19494570
Abstract
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.
Details
- Title: Subtitle
- Therapeutic Regulation of Gene Expression in the Inner Ear using RNA Interference
- Creators
- Yukihide Maeda - aMolecular Otolaryngology Research Laboratories, Department of Otolaryngology, Head and Neck Surgery, bMedical Scientist Training Program, and cInterdepartmental PhD Genetics Program, University of Iowa, Iowa City, Iowa, USAAbraham M Sheffield - aMolecular Otolaryngology Research Laboratories, Department of Otolaryngology, Head and Neck Surgery, bMedical Scientist Training Program, and cInterdepartmental PhD Genetics Program, University of Iowa, Iowa City, Iowa, USARichard J.H Smith - aMolecular Otolaryngology Research Laboratories, Department of Otolaryngology, Head and Neck Surgery, bMedical Scientist Training Program, and cInterdepartmental PhD Genetics Program, University of Iowa, Iowa City, Iowa, USA
- Contributors
- A.F Ryan (Editor)
- Resource Type
- Book chapter
- Publication Details
- Gene Therapy of Cochlear Deafness, pp.13-36
- Series
- Advances in Oto-Rhino-Laryngology
- DOI
- 10.1159/000218205
- PMID
- 19494570
- PMCID
- PMC2867253
- NLM abbreviation
- Adv Otorhinolaryngol
- eISSN
- 1662-2847
- ISSN
- 0065-3071
- Publisher
- S. Karger AG; Basel, Switzerland
- Number of pages
- 24
- Language
- English
- Date published
- 05/2009
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Otolaryngology; Internal Medicine
- Record Identifier
- 9984006364002771
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