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

Abstract：

: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.

journal_name

Nat Med

journal_title

Nature medicine

authors

Lentz JJ,Jodelka FM,Hinrich AJ,McCaffrey KE,Farris HE,Spalitta MJ,Bazan NG,Duelli DM,Rigo F,Hastings ML

doi

10.1038/nm.3106

subject

Has Abstract

pub_date

2013-03-01 00:00:00

pages

345-50

issue

3

eissn

1078-8956

issn

1546-170X

pii

nm.3106

journal_volume

19

pub_type

杂志文章

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