ERC Proof of Concept: Coiled-coil mediated exonuclease tethering technology for the enhancement of CRISPR gene editing; Principal investigator: prof. dr. Roman Jerala
Designed coiled-coil peptides were applied for tethering of Cas9 and exonuclease in a noncovalent manner, which substantially improved the efficiency of gene inactivation with potential applications in medicine, agriculture, biotechnology. We filed a patent application: Coiled-coil mediated tethering of CRISPR-CAS and exonucleases for enhanced genome editing: European Patent Application EP19192490.1, 2019-08-20. München: European Patent Office. This invention was the foundation of the ERC PoC project CCEdit that started in 2020, within which we are further developing and translating this invention towards tangible biotechnological and medical applications.
With enhanced CRISPR/Cas system termed CCExo we recruited the exonuclease to the cleavage site and robustly increased gene knock-out. CCExo exhibited increased deletion size and enhanced gene inactivation efficiency. Targeting a sequence-specific oncogenic chromosomal translocation using CCExo in cells of chronic myelogenous leukemia patients and in an animal model led to the reduction or elimination of cancer (Lainšček et al., Nat. Comm. 2022).
After initial 18 months, the project was extended until January 31st 2022.
Project web page: https://ccedit.si/
ERC CCedit team:
prof. dr. Roman Jerala, principal investigator
dr. Duško Lainšček
Tomaž Bizjak
Acronym: CCedit
Project ID: 899259
This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No 899259).