Project description DEENESFRITPL Treating hearing loss via gene therapy approaches Millions of people worldwide suffer from hearing loss due to ageing, congenital causes or prolonged exposure to loud noises. The EU-funded iHEAR project is working towards a gene therapy approach to treat hearing loss. The project involves the investigation of the best vector to transfer therapeutic genes into the cells responsible for sensorial neural hearing loss, the inner ear hair cells and spiral ganglion neurons. Researchers will use cells from patients suffering from hearing loss as a model for testing the gene therapy and gene editing strategies. Collectively, the iHEAR project will advance current tools for studying and treating hearing loss. Show the project objective Hide the project objective Objective To address the substantial financial and social burden caused by hearing loss in 360 million people world-wide, I aim to improve hearing via gene therapy to correct inherited and protect from acquired hearing loss. In vitro experiments will establish the best vector configurations for transfer of therapeutic genes and miRNAs into inner ear hair cells (HC) and spiral ganglion neurons (SGN). The efficiency of the best-performing vector designs will then be explored in vivo using fluorescent marker proteins. Cell-type specific and inducible promoters as well as receptor-targeted vectors will be employed as a safety measure and to ensure transgene expression in HC and SGN target cells. Once efficient transduction of appropriate target cells and proper expression of therapeutic proteins are demonstrated, I will perform proof-of-concept studies in hearing loss models, incl. established mouse models, to correct (WP1) or protect (WP2) from impaired hearing. To ensure translatability of these findings, I will generate human induced pluripotent stem cells (iPSC) from patients with hearing loss (WP3), so that I can test optimized constructs in human otic cells. Moreover, I have access to a collection of well-characterized samples from over 600 hearing loss patients, including children with congenital hearing loss in whom many novel monogenetic alterations were identified. These resources provide the unique opportunity to generate a novel toolbox for the treatment of hearing loss. In addition to lentiviral and adeno-associated viral (AAV) vector delivery of corrective or protective genes to treat hearing loss, I will apply state-of-the-art genome editing tools to model and correct mutations causative for hearing loss in cell lines, primary cells from murine models, human patients and patient-derived iPSC. This work will contribute to development of clinically translatable approaches for precision medicine strategies to improve hearing loss treatment. Fields of science medical and health sciencesmedical biotechnologygenetic engineeringgene therapynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesmedical biotechnologycells technologiesstem cellsnatural sciencesbiological sciencesgeneticsmutationmedical and health scienceshealth sciencespersonalized medicine Keywords gene therapy viral vectors gene editing iPS cells hearing loss mouse models Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-2018-COG - ERC Consolidator Grant Call for proposal ERC-2018-COG See other projects for this call Funding Scheme ERC-COG - Consolidator Grant Host institution MEDIZINISCHE HOCHSCHULE HANNOVER Net EU contribution € 1 999 500,00 Address Carl-Neuberg-Strasse 1 30625 Hannover Germany See on map Region Niedersachsen Hannover Region Hannover Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 1 999 500,00 Beneficiaries (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all MEDIZINISCHE HOCHSCHULE HANNOVER Germany Net EU contribution € 1 999 500,00 Address Carl-Neuberg-Strasse 1 30625 Hannover See on map Region Niedersachsen Hannover Region Hannover Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 1 999 500,00
