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Rescue of hearing and vestibular function by antisense oligonucleotides in a mouse model of human deafness.

Authors: Lentz, JJ  Jodelka, FM  Hinrich, AJ  McCaffrey, KE  Farris, HE  Spalitta, MJ  Bazan, NG  Duelli, DM  Rigo, F  Hastings, ML 
Citation: Lentz JJ, etal., Nat Med. 2013 Mar;19(3):345-50. doi: 10.1038/nm.3106. Epub 2013 Feb 4.
Pubmed: (View Article at PubMed) PMID:23380860
DOI: Full-text: DOI:10.1038/nm.3106

Hearing impairment is the most common sensory disorder, with congenital hearing impairment present in approximately 1 in 1,000 newborns. Hereditary deafness is often mediated by the improper development or degeneration of cochlear hair cells. Until now, it was not known whether such congenital failures could be mitigated by therapeutic intervention. Here we show that hearing and vestibular function can be rescued in a mouse model of human hereditary deafness. An antisense oligonucleotide (ASO) was used to correct defective pre-mRNA splicing of transcripts from the USH1C gene with the c.216G>A mutation, which causes human Usher syndrome, the leading genetic cause of combined deafness and blindness. Treatment of neonatal mice with a single systemic dose of ASO partially corrects Ush1c c.216G>A splicing, increases protein expression, improves stereocilia organization in the cochlea, and rescues cochlear hair cells, vestibular function and low-frequency hearing in mice. These effects were sustained for several months, providing evidence that congenital deafness can be effectively overcome by treatment early in development to correct gene expression and demonstrating the therapeutic potential of ASOs in the treatment of deafness.

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CRRD Object Information
CRRD ID: 8695937
Created: 2014-08-06
Species: All species
Last Modified: 2014-08-06
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.