Descripción del proyecto
Tratar la hipoacusia con métodos de genoterapia
En todo el mundo, millones de personas sufren de hipoacusia debido al envejecimiento, a causas congénitas o a una exposición prolongada a ruidos fuertes. El proyecto iHEAR, financiado con fondos europeos, está desarrollando un método de genoterapia para tratar la hipoacusia. El proyecto implica la investigación del mejor vector para transferir genes terapéuticos a las células responsables de la hipoacusia neurosensorial: las células ciliadas del oído interno y las neuronas del ganglio espiral. Los investigadores utilizarán células de pacientes con hipoacusia como modelo para probar las estrategias de genoterapia y de edición genética. En conjunto, el proyecto iHEAR mejorará las herramientas actuales para estudiar y tratar la hipoacusia.
Objetivo
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.
Ámbito científico
- medical and health sciencesmedical biotechnologygenetic engineeringgene therapy
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- medical and health sciencesmedical biotechnologycells technologiesstem cells
- natural sciencesbiological sciencesgeneticsmutation
- medical and health scienceshealth sciencespersonalized medicine
Palabras clave
Programa(s)
Régimen de financiación
ERC-COG - Consolidator GrantInstitución de acogida
30625 Hannover
Alemania