Revitalizing the heart: cutting-edge nucleic acid therapies in cardiac regeneration

Abstract

Heart failure (HF) arises from cardiac injury and subsequent loss of contractile cells. While some organisms can regenerate cardiac tissue through cardiomyocyte proliferation, the adult mammalian heart has limited regenerative capacity due to cardiomyocyte replication ceasing shortly after birth. To enhance proliferation in the adult heart, we aim to identify master regulators of proliferation. In Professor Mauro Giacca’s laboratory, human-specific microRNAs (miRNAs) like miR199a-3p or miR-1825 have been identified as potential enhancers of cardiomyocyte proliferation. My PhD will evaluate these miRNAs using different delivery methods, comparing viral vectors with lipid nanoparticle (SNALP) technology. Additionally, I will adapt CycleTrack, a tool for labelling mitotic cells, to study cardiomyocyte replication accurately in response to these miRNAs. By assessing these approaches in human myocardial slices, this work seeks to uncover the molecular mechanisms of pro-proliferative miRNAs and pave the way for future clinical interventions targeting heart regeneration. In this Student Focus article, I also highlight another aspect: the framework used to address complex biological questions is crucial in shaping the answers we seek. What intrigues me most about my research is the interplay between elucidating discrete molecular pathways and employing holistic approaches to understand cardiac proliferation.