Description du projet
Faire progresser les techniques d’édition du génome
Les technologies CRISPR ont révolutionné l’édition du génome en permettant une modification précise de l’ADN dans les organismes vivants. Elles sont basées sur les mécanismes de défense naturels des bactéries contre les virus. Malgré leur potentiel évident, les faibles fréquences d’édition posent des problèmes qui requièrent un examen approfondi. Financé par le Conseil européen de la recherche, le projet CRISPR-SELECT initie une avancée dans la sélection des cellules modifiées en éliminant celles qui ne le sont pas. Cette approche promet d’augmenter considérablement les fréquences d’édition et d’alléger le fardeau de la sélection dans diverses applications d’édition du génome. La proposition présente des expériences de validation du concept sur des cellules humaines, explorant les applications potentielles de cette innovation technologique.
Objectif
CRISPR technologies have revolutionized genome editing in medicine, agriculture, biotechnology, and life-sciences research with their ability to generate virtually any DNA edit at any genomic site in any organism. However, editing frequencies can be restrictively low, requiring extensive screening to identify cells harboring desired edits. What remains elusive is a way to greatly boost the frequency of editing. While characterizing CRISPR-Cas systems, bacterial defense systems and the source of CRISPR technologies, we discovered a new mechanism that could kill unedited cells yet spare edited cells, regardless of the type of gene edit. This versatile and sequence-specific approach can be described as programmable counter-selection, as undesired cells are targeted for removal, and those cells can be targeted in a programmable way. If proven, this capability could radically boost the effective editing frequencies by removing unedited cells regardless of the underlying edit, providing much-needed relief to the burden of screening imposed on diverse genome-editing applications. Here, we propose to perform proof-of-concept experiments demonstrating this capability in human cells while exploring which editing applications would best benefit from this capability. The associated tasks build on my extensive work at the interface of CRISPR biology and technologies and leverages his numerous academic and industrial contacts. I ultimately aim to translate a novel biological insight from my group’s ERC Consolidator project into an innovative foundational technology, with a clear path toward its broad use in genome editing.
Champ scientifique
Mots‑clés
Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Régime de financement
HORIZON-ERC-POC - HORIZON ERC Proof of Concept GrantsInstitution d’accueil
38124 Braunschweig
Allemagne