Targeted Allele Suppression Prevents Progressive Hearing Loss in the Mature Murine Model of Human TMC1 Deafness.
Mol Ther
; 27(3): 681-690, 2019 03 06.
Article
en En
| MEDLINE
| ID: mdl-30686588
ABSTRACT
Hearing loss is the most common human sensory deficit. Its correction has been the goal of several gene-therapy based studies exploring a variety of interventions. Although these studies report varying degrees of success, all treatments have targeted developing inner ears in neonatal mice, a time point in the structural maturation of the cochlea prior to 26 weeks gestational age in humans. It is unclear whether cochlear gene therapy can salvage hearing in the mature organ of Corti. Herein, we report the first study to test gene therapy in an adult murine model of human deafness. Using a single intracochlear injection of an artificial microRNA carried in an AAV vector, we show that RNAi-mediated gene silencing can slow progression of hearing loss, improve inner hair cell survival, and prevent stereocilia bundle degeneration in the mature Beethoven mouse, a model of human TMC1 deafness. The ability to study gene therapy in mature murine ears constitutes a significant step toward its translation to human subjects.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Sordera
/
Vectores Genéticos
/
Proteínas de la Membrana
Límite:
Animals
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Humans
Idioma:
En
Revista:
Mol Ther
Asunto de la revista:
BIOLOGIA MOLECULAR
/
TERAPEUTICA
Año:
2019
Tipo del documento:
Article
País de afiliación:
Japón