title: RNA Interference Prevents Autosomal-Dominant Hearing Loss.
abstract: Hearing impairment is the most common sensory deficit. It is frequently caused by the expression of an allele carrying a single dominant missense mutation. Herein, we show that a single intracochlear injection of an artificial microRNA carried in a viral vector can slow progression of hearing loss for up to 35 weeks in the Beethoven mouse, a murine model of non-syndromic human deafness caused by a dominant gain-of-function mutation in Tmc1 (transmembrane channel-like 1). This outcome is noteworthy because it demonstrates the feasibility of RNA-interference-mediated suppression of an endogenous deafness-causing allele to slow progression of hearing loss. Given that most autosomal-dominant non-syndromic hearing loss in humans is caused by this mechanism of action, microRNA-based therapeutics might be broadly applicable as a therapy for this type of deafness.
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA; Molecular Otolaryngology and Renal Research Laboratories, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Seiji B
authors.initials: SB
authors.lastname: Shibata
authors.affiliation: Molecular Otolaryngology and Renal Research Laboratories, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA; Interdisciplinary Graduate Program in Molecular & Cellular Biology, Graduate College, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Paul T
authors.initials: PT
authors.lastname: Ranum
authors.affiliation: Molecular Otolaryngology and Renal Research Laboratories, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA; Department of Otorhinolaryngology, Shinshu University School of Medicine, Matsumoto, Nagano 3908621, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Moteki
authors.affiliation: Department of Otolaryngology, F.M. Kirby Neurobiology Center, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Bifeng
authors.initials: B
authors.lastname: Pan
authors.affiliation: Molecular Otolaryngology and Renal Research Laboratories, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Alexander T
authors.initials: AT
authors.lastname: Goodwin
authors.affiliation: Department of Communication Sciences and Disorders, College of Liberal Arts and Sciences, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Shawn S
authors.initials: SS
authors.lastname: Goodman
authors.affiliation: Department of Communication Sciences and Disorders, College of Liberal Arts and Sciences, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Abbas
authors.affiliation: Department of Otolaryngology, F.M. Kirby Neurobiology Center, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Holt
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA; Molecular Otolaryngology and Renal Research Laboratories, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA; Interdisciplinary Graduate Program in Molecular & Cellular Biology, Graduate College, University of Iowa, Iowa City, IA 52242, USA; Iowa Institute of Human Genetics, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA. Electronic address: richard-smith@uiowa.edu.
authors.forename: Richard J H
authors.initials: RJH
authors.lastname: Smith
mesh_terms: D000818:Animals; D001306:Auditory Pathways; D000229:Dependovirus / Q000235:genetics; D034381:Hearing Loss / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D006801:Humans; D040542:Mechanotransduction, Cellular; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D051379:Mice; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D035683:MicroRNAs / Q000008:administration & dosage / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics*; D034622:RNA Interference
chemical_list: D008565:Membrane Proteins; D035683:MicroRNAs; C514628:TMC1 protein, mouse; C575755:TMC2 protein, mouse