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Project

Development of a CRISPR-nuclease gene therapy to cure deafness in DFNA9 patients.

Hearing impairment is the most frequent sensory deficit in the human population, affecting 440 million people worldwide, whereby loss of hearing and balance has a significant impact on quality of life and society. Hearing loss is also listed by the World Health Organization as a priority disease for research into therapeutic interventions to address public health needs. DFNA9 (DeaFNess Autosomal 9) is an autosomal dominant hearing disorder caused by a heterozygous gain-of-function mutation in the COCH gene (Coagulation Factor C Homology) and is characterized by progressive late-onset (3rd-5th decade) sensorineural hearing loss (SNHL) and deafness. Within Belgium and the Netherlands, there are >1000 patients affected by the p.P51S COCH mutation, who – in the current absence of a disease modifying therapy – will develop deafness. A promising approach to tackle the pathophysiological mechanism of DFNA9 and stop or delay the onset of SNHL is to introduce a CRISPR-Cas9-based therapy into the inner ear, delivered by an AAV vector to disrupt or downregulate the expression of (mutant) COCH. In this project, I will phenotype a newly established humanized DFNA9 mouse model and assess whether in vivo delivery of a CRISPR-nuclease using an AAV-based viral vector leads to specific disruption of COCH.
Date:1 Oct 2022 →  Today
Keywords:HEARING & DEAFNESS, COCHLEA, GENE THERAPY
Disciplines:Otology