Adeno-associated viral vector administration to the inner ear and phenotype evaluation in a mouse model of hearing...

Hearing loss is the most common sensory impairment in the population, with more than 400 million affected worldwide. Over half the cases of congenital hearing loss have a genetic cause, ∼80 % of which are autosomal recessive with a prevalence of about 1-2 every 1000 births. Gene therapy would represent a curative option for these patients, and adeno-associated viral vectors (AAVs) have become the flagship delivery vehicle for in vivo gene therapy, especially for local delivery and small organ targeting. However, their preclinical development for hearing loss is slower than for other indications due to the inaccessible nature of the cochlea and the limited availability of mouse models that accurately reproduce the phenotype observed in humans. In this book chapter we detail the basic methodology for gene therapy administration to the inner ear in a mouse model of hereditary hearing loss, as well as cellular and functional analysis of cochlear functions.