Inner ear gene therapy to prevent deafness in DFNA9.

Hearing loss has a significant impact on quality of life and society in general. Hearing impairment is the most frequent sensory deficit in human populations, affecting 360 million people worldwide. It was listed by the World Health Organization as one of the priority diseases for research into therapeutic interventions to address public health needs. DFNA9 is a dominant hereditary disorder, caused by heterozygote mutations in the COCH gene, which progressively leads to bilateral deafness and balance loss by the age of 50-70 years. Currently, no treatment is available to prevent hearing loss or balance loss in DFNA9 patients. Local gene therapy to restore hearing or prevent hearing loss has been studied in neonatal mouse models for several years. Currently, a clinical study is ongoing in adult patients with profound hearing loss to restore hair cells by injecting virus-based vectors -carrying correcting genetic information- directly into the inner ear. In this project, we aim to generate an inner ear gene therapy tool to prevent hearing loss in a pre-clinical mouse model of DNFA9. Using Adeno-associated virus (AAV)-based vectors, we will apply CRISPR-Cpf1 genome engineering technology to target directly within in the cochlea Coch genomic DNA in a safe and effective way in order to disrupt expression of the mutant (and wild type) Coch protein before onset of disease. Hereby, we expect to reduce or prevent DNFA9-associated sensorineural hearing loss.

Keywords:DFNA9, MOUSE TRANSGENESIS, HEARING LOSS, GENE THERAPY

Disciplines:Genetics, Systems biology, Molecular and cell biology, Otorhinolaryngology, Speech, language and hearing sciences