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Tmc gene therapy restores auditory function in deaf mice.

Abstract：

:Genetic hearing loss accounts for up to 50% of prelingual deafness worldwide, yet there are no biologic treatments currently available. To investigate gene therapy as a potential biologic strategy for restoration of auditory function in patients with genetic hearing loss, we tested a gene augmentation approach in mouse models of genetic deafness. We focused on DFNB7/11 and DFNA36, which are autosomal recessive and dominant deafnesses, respectively, caused by mutations in transmembrane channel-like 1 (TMC1). Mice that carry targeted deletion of Tmc1 or a dominant Tmc1 point mutation, known as Beethoven, are good models for human DFNB7/11 and DFNA36. We screened several adeno-associated viral (AAV) serotypes and promoters and identified AAV2/1 and the chicken β-actin (Cba) promoter as an efficient combination for driving the expression of exogenous Tmc1 in inner hair cells in vivo. Exogenous Tmc1 or its closely related ortholog, Tmc2, were capable of restoring sensory transduction, auditory brainstem responses, and acoustic startle reflexes in otherwise deaf mice, suggesting that gene augmentation with Tmc1 or Tmc2 is well suited for further development as a strategy for restoration of auditory function in deaf patients who carry TMC1 mutations.

journal_name

Sci Transl Med

journal_title

Science translational medicine

authors

Askew C,Rochat C,Pan B,Asai Y,Ahmed H,Child E,Schneider BL,Aebischer P,Holt JR

doi

10.1126/scitranslmed.aab1996

subject

Has Abstract

pub_date

2015-07-08 00:00:00

pages

295ra108

issue

295

eissn

1946-6234

issn

1946-6242

pii

7/295/295ra108

journal_volume

7

pub_type

杂志文章

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