Objective
During the COVID-19 pandemic, we witnessed the application of mRNA vaccines for SARS-CoV-2, paving the way for the widespread use During the COVID-19 pandemic, we witnessed the application of mRNA vaccines for SARS-CoV-2, paving the way for the widespread use of therapeutic mRNAs in medicine. However, lack of knowledge regarding mRNA metabolism in vivo limits the optimization and refinement of such therapies. Our preliminary data, acquired via Direct RNA Sequencing (DRS), shows that variability of poly(A) tail length and, therefore, stability of endogenous and therapeutic mRNAs in different tissues and cell types is much larger than previously thought.
Here, we propose the ViveRNA project, which will enhance the DRS (eDRS) pipeline and combine it with analyses of mouse models, primary cell cultures, and synthetic biology approaches to examine the nature of mRNA turnover in vivo and characterize the metabolism of endogenous and administered mRNAs. The goal of the ViveRNA project is to elucidate the complexity of mRNA lifetime regulation. Specifically, our aims are:
• Part 1: Construction of an enhanced nanopore Direct RNA Sequencing pipeline (eDRS) for comprehensive analyses of mRNA metabolism. eDRS will assess the composition and lengths of poly(A) tails, modifications, isoforms, and dynamics.
• Part 2: Comprehensive analysis of the lifecycle of endogenous mRNAs, analyzing: dynamics, ribosome association, and poly(A) tail metabolism in organs and primary cells and providing insights into the role of particular enzymes. The reach data resource will help designing better mRNA therapeutics and enable the formulation of testable mechanistic hypotheses.
• Part 3: Description of the metabolism of therapeutic mRNAs in relevant cell types and tissues. Then, together with the knowledge gained in Part 2, the design of more stable mRNAs with therapeutic potential will be initiated.
The ViveRNA project will facilitate the rational design of next-generation mRNA therapeutics.
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.
- medical and health sciences health sciences public health epidemiology pandemics
- medical and health sciences health sciences infectious diseases RNA viruses coronaviruses
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs vaccines
- natural sciences biological sciences genetics RNA
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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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-2022-ADG
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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.
02109 Warszawa
Poland
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.