Project description
RNAylated proteins as a tool for advanced RNA therapeutics
NAD-capped RNAs can bind to target proteins via the ART ModB enzyme in a process known as RNAylation. This biomolecule, the RNAylated protein, enables targeted intracellular delivery, allowing components to function synergistically. RNAylated proteins could form the foundation for engineering cellular functions and developing advanced RNA therapeutics. The ERC-funded NAD-ART project seeks to establish RNAylated proteins as a novel tool for regulating cellular processes. The project will define design principles for these proteins to enhance control over cellular functions and develop strategies for delivering RNAylated proteins into specific cell types for precise localisation. Ultimately, it will apply these principles to target the tumour suppressor protein p53, regulating it through translation, transcription, or editing.
Objective
Background: We discovered that NAD-capped RNAs can be covalently attached to specific target proteins by the phage T4 ADP-ribosyltransferase (ART) ModB, which we term RNAylation.
Scientific problem:
RNA therapy has almost limitless yet unexplored potential. Its translation into the clinics, however, requires optimal RNA delivery with high RNA stability, efficient cellular internalisation and precise target affinity.
Hypothesis: Protein-RNA interactions are ubiquitous and central in biological control. I hypothesise that conjugating a NAD-capped nucleic acid to a protein catalysed by an ART generates a novel biomolecule – the RNAylated protein – with unique functionalities. The covalently linked protein or nucleic acid can trigger a directed intracellular delivery, where both, the protein and the nucleic acid, can become functionally active. This allows targeted modulation of translation or transcription, or editing. RNAylated proteins may provide a platform to engineer the cell and represent a starting point for the creation of next generation RNA therapeutics.
Objectives:
This project aims to establish RNAylated proteins as a fundamentally novel tool to regulate cellular processes. In objective 1, we will define the design principles for RNAylated proteins, allowing to control cellular processes. In objective 2, we will develop delivery strategies to transfer RNAylated proteins in specific cell types and allow for precise cellular localisation. In objective 3, we will combine the design and delivery principles for RNAylated proteins and apply them to target the tumour suppressor protein p53 by regulating translation, transcription or by editing.
Impact: This project will develop RNAylated proteins as next generation RNA therapeutics and deepen our understanding of how a fundamental scientific discovery –the RNAylation of proteins, catalysed by the T4 ART ModB – can be translated into an application.
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 microbiology virology
- natural sciences biological sciences biochemistry biomolecules proteins
- 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)
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Topic(s)
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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.
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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
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2023-STG
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35037 Marburg
Germany
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