Skip to main content
European Commission logo print header

Targeting the miR-106b~25 cluster in pathological Cardiac Hypertrophy

Obiettivo

BACKGROUND: There is a tremendous need to develop novel therapies for heart failure. In particular, sustained pathological hypertrophy, a major predictor of this condition, is a complex process, which involves transcriptional and posttranscriptional regulation of the cardiac genome. There is now clear indication that, besides a few known transcriptional regulators, multiple, still poorly understood cardiac factors are involved in hypertrophy; understanding this complexity is expected to pave to the way to innovative therapies. In particular, recent data demonstrate that dysregulated microRNAs (miRs) are associated with heart failure, and that selective modulation of miRs can provide therapeutic benefits. Our pilot-data show that expression of the miR-106b~25 cluster decreases during pathological hypertrophy in mice and that virus-mediated overexpression of this cluster prevents phenylephrine-induced hypertrophic remodeling. Following bioinformatics screens for potential direct downstream targets of the miR-25~106b cluster, we identified a series of transcription factors, which might play a role in pathological cardiac remodeling.
AIM: To define the functional implication of the miR-106b~25 cluster in pathological cardiac hypertrophy and to exploit this information towards the development of novel therapeutic approaches.
APPROACH: We will identify direct downstream targets of the miR-106b~25 cluster during hypertrophy, by performing Ago2-Immunoprecipitation and by treating neonatal cardiomyocytes with precursors of miR-25, miR-93 and miR-106b, followed by next generation sequencing (Objective 1); We aim to reverse pathological cardiac remodeling and prevent heart failure by delivery of recombinant adeno-associated virus (rAAV9)- miR-106b~25 in mice (Objective 2). The results obtained will generate important intellectual property value and will constitute the basis for further development towards the generation of novel therapies against heart failure.

Invito a presentare proposte

FP7-PEOPLE-2013-IEF
Vedi altri progetti per questo bando

Coordinatore

INTERNATIONAL CENTRE FOR GENETIC ENGINEERING AND BIOTECHNOLOGY
Contributo UE
€ 93 707,40
Indirizzo
PADRICIANO 99
34149 Trieste
Italia

Mostra sulla mappa

Regione
Nord-Est Friuli-Venezia Giulia Trieste
Tipo di attività
Research Organisations
Contatto amministrativo
Decio Ripandelli (Mr.)
Collegamenti
Costo totale
Nessun dato