Objective
Reversing organ failure, a leading cause of death in sepsis, requires specific modulation of biological pathways in endothelial cells, which is currently not possible with the existing drugs available. Employing RNA-based drugs to control protein expression could offer a novel therapeutic strategy in the fight against sepsis.
Circular RNAs (circRNAs) are a new class of non-coding RNAs with a unique closed-loop structure that could help address the current limitations of the RNA drugs in the disease context and open new therapeutic avenues. Therapeutic delivery of engineered synthetic circRNAs can allow taking full advantage of their unique features and functions, including increased intracellular stability, the ability to affect multiple biological pathways by sponging microRNA or proteins, and their potential for cellular context-specific control of protein expression via internal ribosome entry site (IRES)-mediated cap-independent translation.
I recently co-developed methods for the circularization and purification of large synthetic circRNAs, and pioneered their use for robust and stable protein expression in eukaryotic cells, to address the short half-life of mRNA in biological systems. I also synthesized a new type of degradable polymers that enable tissue and cell-type selective delivery of large RNAs with low toxicity.
Building on those findings, CIRCLE aims to expand the toolbox of therapeutic RNAs by engineering novel synthetic circRNAs for modulation of protein expression in sepsis (WP1 and WP2) and investigate the potential of synthetic circRNA delivery for developing RNA-based pharmacological intervention to reverse sepsis-associated lung and kidney failure (WP3 and WP4). By addressing an important gap in the knowledge on the utility of circRNAs for translational research the scientific impact of CIRCLE will extend across the research fields of pharmaceutical sciences, synthetic biology, and medicine.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences chemical sciences polymer sciences
- natural sciences biological sciences genetics RNA
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
MAIN PROGRAMME
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Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-ERC - HORIZON ERC Grants
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2021-STG
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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.
T12 YN60 Cork
Ireland
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.