
CRISPR technologies have revolutionized genome editing: they can modify virtually any DNA-at any genomic site in any organism. However, in many cases, the procedure is inefficient, and the quantity of modified cells is very low. To identify and isolate cells with the desired edits, extensive screening can be required. Relief could come from a mechanism recently discovered by a research team led by the Helmholtz Institute Würzburg. The further exploration of this mechanism is now supported by the European Research Council (ERC) through an ERC Proof of Concept Grant of 150,000 euros.
As part of a project already funded by an ERC Consolidator Grant, the team led by department head Chase Beisel is researching CRISPR-Cas systems at the Würzburg Helmholtz Institute for RNA-based Infection Research (HIRI), a site of the Braunschweig Helmholtz Centre for Infection Research (HZI) in cooperation with the Julius-Maximilians-Universität (JMU). These systems, which form the natural immune defense of bacteria against viruses, are the foundation of CRISPR technologies and are commonly referred to as "gene scissors."
The researchers identified a new mechanism that kills unmodified cells while sparing modified ones. "The method relies on the Cas12a2 nucleases we recently characterized together with Benson Hill, Inc. (Missouri) and Utah State University in the U.S., and can be described as programmable counter-selection: undesired cells can-in theory-be easily and specifically removed," Chase Beisel, who also holds a professorship at the Faculty of Medicine of the JMU, explains. "This would provide much-needed relief in screening for various applications of genome editing," adds the CRISPR expert.
In the project, Beisel will conduct proof-of-concept experiments together with researchers at Utah State University, the University of Utah and BRAIN Biotech AG. The researchers will evaluate the mechanism in human cells and investigate which editing applications would benefit most from the method.
"The associated tasks build on my extensive work at the interface of CRISPR biology and technologies. I ultimately aim to translate a novel biological insight from my group’s ERC project into an innovative foundational technology that could find broad application in genome editing," he summarizes. If successfully developed, the method could simplify the generation of cell-based therapies and accelerate the generation of edited cells for studying the mechanistic basis of human diseases.