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Project

Combinatorial, High-throughput organoid screens for personalized medicine

Perspectives for patients with cystic fibrosis (CF) have dramatically changed over the last few years, with the advent of CFTR modulators, a new treatment class comprising several mutation-specific drugs. Recent drug development efforts are directed to the most frequent CFTR mutation (F508del) and a handful of less frequent mutations, excluding around 10% of patients with only rare mutations, who depend on academic research innovation and public-private partnerships to provide efficient treatments. For these patients, current personalized medicine approaches are labor and cost intensive. Therefore, innovations increasing the throughput paralleled by a reduction in sample size and reagent volumes, would be of great economical and societal value. In this project, we will investigate, on biobanked rectal organoids of ~70 CF patients with rare mutations ineligible for licensed drugs: (1) Novel combinations of CFTR modulators, approved or in late development phase, in their ability to restore CFTR function (2) For mutations not rescuable by compounds, we will develop tailored CRISPR-Cas-based gene editing strategies. To scale up the process, we will develop a novel microfluidic High-Throughput Screening (HTS) platform, with increased test capacity on smaller organoid samples, opening up avenues for rapid and ex-vivo HTS for drug and gene editing therapies in a personalized medicine approach.

Date:19 Apr 2022 →  Today
Keywords:Combinatorial screens, Droplet-based microfluidics, Personalized medicine
Disciplines:Microfluidics/flow chemistry, Fluid physics and dynamics, Nanochemistry, Medicinal and biomolecular chemistry not elsewhere classified, Bio-organic chemistry, Micro- and nanoelectromechanical systems, Nanofabrication and nanomanufacturing, Nanomaterials, Nanobiotechnology, Medical nanotechnology, Particle design and technology, Biomedical image processing, Cell engineering, Photonics, light and lighting, Robotics and automatic control, Medical biotechnology diagnostics
Project type:PhD project