In Vivo Gene Transfer into Neonatal Mice Cochlea Using Adeno- Associated Viral Vectors:

Objectives:Although sensory hearing loss is the most common sensory disorder, with more than 75% of genetic origin, there are no curative treatments available. A promising approach to restore inherited hearing loss consists of introducing a functional copy of the deficient gene using gene therapy. The present study develops a non-invasive surgical approach using adeno-associated viruses (AAV) vector to introduce reporter genes into neonatal mice cochleae, without affecting the normal development of hearing.Methods:AAV2, AAV2/8, AAV2/1, and AAV8, carrying green fluorescent protein (GFP) reporter gene, were tested using 150 neonatal mice. Two microliters of vectors, with titer of 1013 vg/ml, were injected into the scala tympani through the round window. Two weeks after viral injection, evoked auditory brain-stem responses (ABR) were recorded; cellular expression and distribution of GFP were analyzed by immunohistochemistry and confocal imaging.Results:AAV2/8 vector transduced cochlear inner hair cells with ...