biostudies-literatureUnknown7(4)Higashikuni Y<h4>Background</h4>Cardiomyocyte loss occurs in acute and chronic cardiac injury, including cardiotoxicity due to chemotherapeutics like doxorubicin, and contributes to heart failure development. There is a pressing need for cardiac-specific therapeutics that target cardiomyocyte loss, preventing chemotherapy complications without compromising chemotherapeutic efficacy.<h4>Objectives</h4>The authors employed massively parallel combinatorial genetic screening to find microRNA (miRNA) combinations that promote cardiomyocyte survival.<h4>Methods</h4>CombiGEM (combinatorial genetics en masse) screening in a cardiomyocyte cell line was followed by validation in the original cell type and screening in primary cardiomyocytes. The top combination was tested in mouse and developing zebrafish modelsJACC. CardioOncology396-410https://www.ebi.ac.uk/biostudies/studies/S-EPMC12228136biostudies-literatureMitigation of Doxorubicin Cardiotoxicity With Synergistic miRNA Combinations Identified Using Combinatorial Genetics en masse (CombiGEM).PMC12228136Takeda NPlatt CObana TYeri ALu TKMatsumura TBayer ALLiu WUosaki HRosenzweig AKuznetsov AGuerra JRBTokuyama TChen WCWHigashikuni YTurissini CShibayama KWhipple HKitchen RRAsnani AHHastings MHTorizal FGfalseMitigation of Doxorubicin Cardiotoxicity With Synergistic miRNA Combinations Identified Using Combinatorial Genetics en masse (CombiGEM).<h4>Background</h4>Cardiomyocyte loss occurs in acute and chronic cardiac injury, including cardiotoxicity due to chemotherapeutics like doxorubicin, and contributes to heart failure development. There is a pressing need for cardiac-specific therapeutics that target cardiomyocyte loss, preventing chemotherapy complications without compromising chemotherapeutic efficacy.<h4>Objectives</h4>The authors employed massively parallel combinatorial genetic screening to find microRNA (miRNA) combinations that promote cardiomyocyte survival.<h4>Methods</h4>CombiGEM (combinatorial genetics en masse) screening in a cardiomyocyte cell line was followed by validation in the original cell type and screening in primary cardiomyocytes. The top combination was tested in mouse and developing zebrafish models2025-01-01T00:00:00Z2025 Jun2026-06-02T20:17:45.294Z2026-04-20T03:10:07.849ZS-EPMC122281364036632510.1016/j.jaccao.2025.03.007