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Harnessing a novel CRISPR nuclease for programmable counterselection in human cells

Project description

Advancing genome editing techniques

CRISPR technologies enable precise DNA modification in living organisms and have revolutionised genome editing. They are based on the natural defence mechanisms of bacteria against viruses. Despite their potential, low editing frequencies pose challenges, necessitating extensive screening. Funded by the European Research Council, the CRISPR-SELECT project proposes a breakthrough in the selection of edited cells by eliminating unedited ones. This approach promises to significantly enhance editing frequencies, alleviating the screening burden across various genome-editing applications. The proposal outlines proof-of-concept experiments in human cells, exploring the potential applications of this technological innovation.

Objective

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.

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Topic(s)

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Funding Scheme

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HORIZON-ERC-POC - HORIZON ERC Proof of Concept Grants

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Call for proposal

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(opens in new window) ERC-2023-POC

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Host institution

HELMHOLTZ-ZENTRUM FUR INFEKTIONSFORSCHUNG GMBH
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 150 000,00
Address
INHOFFENSTRASSE 7
38124 Braunschweig
Germany

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Region
Niedersachsen Braunschweig Braunschweig, Kreisfreie Stadt
Activity type
Research Organisations
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Total cost

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Beneficiaries (1)

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