non coding RNA therapetics to elicit cardiac regeneration in ischemic heart disease
Description: Current therapeutic strategies for ischemic heart disease do not rescue the damaged myocardium. Cardiac tissue regeneration represents a ground-breaking new strategy to treat this condition. Accumulating experimental evidence has uncovered a minor cardiomyocyte turnover in the adult human heart being insufficient to replace the millions of lost cardiac cells upon injury. Recent evidence highlights the potential of cardiac regeneration by stimulation of
proliferation of already existing (endogenous) cardiomyocytes and promotion of angiogenesis in human cardiac microvascular endothelial cells. Non-coding RNAs (ncRNAs), microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) have emerged as powerful posttranscriptional regulators of cellular function and disrupting gene expression using RNA therapeutics targeting these regulators is an appealing strategy to elicit (transient) cardiac regeneration and treat ischemic heart disease. The RECREATE consortium aims to unravel endogenous ncRNA expression and transcriptomes in cardiomyocytes and endothelial cells from experimental models with natural and lifelong regenerative ability (zebrafish, African spiny mouse) and compares those with mammalian cardiac disease models with low regenerative potential (mouse and human) to uncover new and bring forward pre-existing regenerative candidates. Mechanistic
characterisation of ncRNAs will be carried out by pull-down techniques, coupled NGS and mass-spec technologies. Functional and therapeutic perspectives will be evaluated by experimental delivery of RNA therapeutics and viral vectors of the most prominent candidate regenerative ncRNAs in cardioids as miniaturized versions of the human heart produced in vitro in three dimensions (3D), mouse models of ischemic heart disease and human myocardial
slices. These aims will deeply scope into the inventory, the function and potential therapeutic perspective of regenerative ncRNAs. RECREATE brings together a highly synergetic network of leading scientists. Their respective labs have a strong focus on studying the functional contribution of ncRNAs in the cardiovascular system using innovative models or patients to evaluate aspects of regenerative medicine and a strong publication record that documents their specific expertise. Each investigates specific aspects of ncRNAs, which combine ideally to comprehensively address the role of ncRNAs in cardiac regeneration. Ultimately, the purpose of RECREATE is to bring forward novel ncRNA therapeutics with the potential for a ground-breaking change in the management of patients with ischemic heart disease.
Funder: Narodowe Centrum Badań i Rozwoju
Amount: PLN 1,835,000
Funding type: research
Funder scheme: Inna
Start date: 2025-05-01
End date: 2028-04-30
Investigator: Tomasz Guzik
Institution: Uniwersytet Jagielloński w Krakowie
Funded outputs count: 0
Funder award ID: E4H/II/81/RECREATE/2025
OpenAlex ID: G63613026