Enhanced viral-mediated cochlear gene delivery in adult mice by combining canal fenestration with round window membrane inoculation.
Sci Rep
; 8(1): 2980, 2018 02 14.
Article
em En
| MEDLINE
| ID: mdl-29445157
ABSTRACT
Cochlear gene therapy holds promise for the treatment of genetic deafness. Assessing its impact in adult murine models of hearing loss, however, has been hampered by technical challenges that have made it difficult to establish a robust method to deliver transgenes to the mature murine inner ear. Here in we demonstrate the feasibility of a combined round window membrane injection and semi-circular canal fenestration technique in the adult cochlea. Injection of both AAV2/9 and AAV2/Anc80L65 via this approach in P15-16 and P56-60 mice permits robust eGFP transduction of virtually all inner hair cells throughout the cochlea with variable transduction of vestibular hair cells. Auditory thresholds are not compromised. Transduction rate and cell tropism is primarily influenced by viral titer and AAV serotype but not age at injection. This approach is safe, versatile and efficient. Its use will facilitate studies using cochlear gene therapy in murine models of hearing loss over a wide range of time points.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Terapia Genética
/
Cóclea
/
Técnicas de Transferência de Genes
/
Surdez
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Fenestração do Labirinto
/
Células Ciliadas Auditivas Internas
/
Perda Auditiva
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Sci Rep
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Estados Unidos