Project description
Targeting non-coding circular RNAs in heart failure therapy
The major causes of heart failure are cardiac remodelling processes at the molecular, cellular and tissue level. The EU-funded REVERSE project will investigate the involvement of the non-coding circular RNA (circRNA) in cardiac injury associated with chemotherapy-induced cardiotoxicity and SARS CoV 2 infection. Multiple molecular circRNA signatures were discovered during the remodelling of cardiac cells and tissues in mice models and humans. The non-coding circRNAs are stable and species-conserved, representing ideal drug targets. The project aims to identify key circRNAs involved in remodelling processes using functional CRISPR-Cas library screening and validation in the human myocardial tissue model. The selected candidates will be tested in both chemotherapy-induced cardiotoxicity and SARS CoV-2-induced cardiac disease models.
Objective
Heart failure (HF) is a most common cause of mortality with currently >60 million of affected patients. Numbers will increase due to socioeconomic factors and as a result of the current COVID-19 pandemic. A major underlying cause of HF are cardiac remodelling processes at the molecular, cellular and tissue level. We will here focus on noncoding circular RNAs (circRNA) involved in two distinct forms of cardiac injury, chemotherapy-induced cardiotoxicity and SARS-CoV-2-infection, where currently no specific treatment strategies are available to reverse disease pathology. First proof-of-concept studies targeting the cardiac remodelling process by noncoding RNA modulation have been pioneered by us and were recently tested in a world-wide first clinical phase 1b study in HF patients. Within the family of non-coding RNAs, circRNAs are stable and species-conserved and thus ideal drug targets. We discovered multiple molecular circRNA signatures during remodelling of cardiac cells and tissues from mice and patients. We now aim to lift our research to its next inflection point with the following steps and interconnected objectives: a) discover key functional circular RNAs involved in remodelling processes by functional CRISPR-Cas library screening; b) validate circRNAs by manipulating human living beating myocardial tissue, c) explore their mode of action; and d) perform targeted cardiac delivery approaches of selected candidates in both chemotherapy-induced cardiotoxicity and SARS-CoV-2-induced cardiac disease models. A combination of bioinformatic, molecular and physiology-based methods, unique established noncoding RNA drug discovery pipelines, availability of modern S3-safety labs, large clinical biobanks and (fresh) human cardiac tissue for slicing preparations form the basis for a successful strategy. REVERSE aims to discover fundamentally new therapeutic entry points for two forms of cardiac injuries, where currently no disease-specific treatments are available.
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.
- social sciences sociology demography mortality
- medical and health sciences health sciences public health epidemiology pandemics
- medical and health sciences basic medicine pathology
- 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)
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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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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.
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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-2021-ADG
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30625 Hannover
Germany
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