Abstract
Hearing loss is the most common sensory deficit and has been recognized by the WHO as a priority disease for research into therapeutic interventions. Deafness Autosomal Dominant 9 (DFNA9) is one of the best-studied forms of dominantly-inherited, adult-onset hearing loss and is characterized by progressive sensorineural hearing loss (SNHL). It is caused by mutations in the COCH gene, which encodes for the protein cochlin. In this project, the applicant presents the development and pre-clinical testing of an optimized delivery method for RNA therapeutics for hearing loss. The applicant will use DFNA9 and the antisense oligonucleotides (ASOs) she validated in vitro, as a case study for this novel treatment paradigm. More specifically, the applicant will go beyond the current state of the art by benchmarking the clinically relevant/feasible intratympanic delivery method and generating a purpose-built hydrogel for ASO treatment. Furthermore, cell-specific uptake of different gapmer ASO chemistries in the inner ear will be studied to achieve targeted delivery. Finally, the applicant will generate data on the pharmacokinetics, safety and efficacy of (gapmer) ASOs in the mammalian inner ear of our genetically engineered humanized DFNA9 mouse model. As such, this project will pave the way for clinical applications of ASOs and other types of gene therapy to target the cochlea for the future treatment of DFNA9 and other inner ear disorders.
Researcher(s)
Research team(s)
Project type(s)