CuRE | Cardiac REgeneration from within

Summary
Biotechnological therapies for patients with myocardial infarction and heart failure are urgently needed, in light of the breadth of these diseases and a lack of curative treatments. CuRE is an ambitious project aimed at identifying novel factors (cytokines, growth factors, microRNAs) that promote cardiomyocyte proliferation and can thus be transformed into innovative therapeutics to stimulate cardiac regeneration. The Project leads from two concepts: first, that cardiac regeneration can be obtained by stimulating the endogenous capacity of cardiomyocytes to proliferate, second that effective biotherapeutics might be identified through systematic screenings both in vivo and ex vivo. In the mouse, CuRE will take advantage of two unique arrayed libraries cloned in adeno-associated virus (AAV) vectors, one corresponding to the secretome (1200 factors) and the other to the miRNAome (800 pri-miRNA genes). Both libraries will be functionally screened in mice to search for factors that enhance cardiac regeneration. This in vivo selection approach will be complemented by a series of high throughput screenings on primary cardiomyocytes ex vivo, aimed at systematically assessing the involvement of all components of the ubiquitin/proteasome pathway, the cytoskeleton and the sarcomere on cell proliferation. Cytokines and miRNAs can both be developed to become therapeutic molecules, in the form of recombinant proteins and synthetic nucleic acids, respectively. Therefore, a key aim of CuRE will be to establish procedures for their production and administration in vivo, and to assess their efficacy in both small and large animal models of myocardial damage. In addition to this translational goal, the project will entail the successful achievement of several intermediate objectives, each of which possesses intrinsic validity in terms of basic discovery and is thus expected to extend technology and knowledge in the cardiovascular field beyond state-of-the art.
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More information & hyperlinks
Web resources: https://cordis.europa.eu/project/id/787971
Start date: 01-01-2019
End date: 30-06-2024
Total budget - Public funding: 2 428 492,00 Euro - 2 428 492,00 Euro
Cordis data

Original description

Biotechnological therapies for patients with myocardial infarction and heart failure are urgently needed, in light of the breadth of these diseases and a lack of curative treatments. CuRE is an ambitious project aimed at identifying novel factors (cytokines, growth factors, microRNAs) that promote cardiomyocyte proliferation and can thus be transformed into innovative therapeutics to stimulate cardiac regeneration. The Project leads from two concepts: first, that cardiac regeneration can be obtained by stimulating the endogenous capacity of cardiomyocytes to proliferate, second that effective biotherapeutics might be identified through systematic screenings both in vivo and ex vivo. In the mouse, CuRE will take advantage of two unique arrayed libraries cloned in adeno-associated virus (AAV) vectors, one corresponding to the secretome (1200 factors) and the other to the miRNAome (800 pri-miRNA genes). Both libraries will be functionally screened in mice to search for factors that enhance cardiac regeneration. This in vivo selection approach will be complemented by a series of high throughput screenings on primary cardiomyocytes ex vivo, aimed at systematically assessing the involvement of all components of the ubiquitin/proteasome pathway, the cytoskeleton and the sarcomere on cell proliferation. Cytokines and miRNAs can both be developed to become therapeutic molecules, in the form of recombinant proteins and synthetic nucleic acids, respectively. Therefore, a key aim of CuRE will be to establish procedures for their production and administration in vivo, and to assess their efficacy in both small and large animal models of myocardial damage. In addition to this translational goal, the project will entail the successful achievement of several intermediate objectives, each of which possesses intrinsic validity in terms of basic discovery and is thus expected to extend technology and knowledge in the cardiovascular field beyond state-of-the art.

Status

SIGNED

Call topic

ERC-2017-ADG

Update Date

27-04-2024
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Horizon 2020
H2020-EU.1. EXCELLENT SCIENCE
H2020-EU.1.1. EXCELLENT SCIENCE - European Research Council (ERC)
ERC-2017
ERC-2017-ADG