Opis projektu
Leczenie ubytku słuchu za pomocą terapii genowej
Miliony ludzi na całym świecie doznają ubytku słuchu z powodu starzenia się, przyczyn wrodzonych lub długotrwałej ekspozycji na głośne dźwięki. Zespół finansowanego ze środków Unii Europejskiej projektu iHEAR prowadzi prace nad zastosowaniem terapii genowej w leczeniu niedosłuchu. Jednym z obszarów prac w ramach projektu jest badanie najlepszego wektora pozwalającego na dostarczenie leczniczych genów do komórek odpowiedzialnych za utratę słuchu, komórek włosowych ucha środkowego oraz neuronów zwoju spiralnego. Badacze zamierzają wykorzystać komórki pochodzące od pacjentów cierpiących na niedosłuch w celu opracowania modelu do testowania strategii terapii genowych i edycji genów. Rezultatem projektu iHEAR będzie rozwój wykorzystywanych obecnie narzędzi do badania i leczenia ubytków słuchu.
Cel
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.
Dziedzina nauki
- 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
Słowa kluczowe
Program(-y)
Temat(-y)
System finansowania
ERC-COG - Consolidator GrantInstytucja przyjmująca
30625 Hannover
Niemcy