A growing body of evidence indicates that cardiac regeneration after myocardial infarction can be achieved by stimulating the endogenous capacity of cardiomyocytes (CMs) to replicate. This process is controlled, both positively and negatively, by a large set of non-coding RNAs (ncRNAs). Some of the microRNAs (miRNAs) that can stimulate CM proliferation is expressed in embryonic stem cells and is required to maintain pluripotency (e.g. the miR-302 similar to 367 cluster). Others also govern the proliferation of different cell types, including cancer cells (e.g. the miR-17 similar to 92 cluster). Additional miRNAs were discovered through systematic screenings (e.g. miR-199a-3p and miR-590-3p). Several miRNAs instead suppress CM proliferation and are involved in the withdrawal of CMs from the cell cycle after birth (e.g. the let-7 and miR-15 families). Similar regulatory roles on CM proliferation are also exerted by a few Long ncRNAs. This body of information has obvious therapeutic implications, as miRNAs with activator function or short antisense oligonucleotides against inhibitory miRNAs or lncRNAs can be administered to stimulate cardiac regeneration. Expression of miRNAs can be achieved by gene therapy using adeno-associated vectors, which transduce CMs with high efficiency. More effective and safer for therapeutic purposes, small nucleic acid therapeutics can be obtained as chemically modified, synthetic molecules, which can be administered through lipofection or inclusion in lipid or polymer nanoparticles for efficient cardiac delivery. The notion that it is possible to reprogramme CMs into a regenerative state and that this property can be enhanced by ncRNA therapeutics remains exciting, however extensive experimentation in large mammals and rigorous assessment of safety are required to advance towards clinical application.

Non-coding RNA therapeutics for cardiac regeneration

Braga, Luca;Secco, Ilaria;Giacca, Mauro
2021-01-01

Abstract

A growing body of evidence indicates that cardiac regeneration after myocardial infarction can be achieved by stimulating the endogenous capacity of cardiomyocytes (CMs) to replicate. This process is controlled, both positively and negatively, by a large set of non-coding RNAs (ncRNAs). Some of the microRNAs (miRNAs) that can stimulate CM proliferation is expressed in embryonic stem cells and is required to maintain pluripotency (e.g. the miR-302 similar to 367 cluster). Others also govern the proliferation of different cell types, including cancer cells (e.g. the miR-17 similar to 92 cluster). Additional miRNAs were discovered through systematic screenings (e.g. miR-199a-3p and miR-590-3p). Several miRNAs instead suppress CM proliferation and are involved in the withdrawal of CMs from the cell cycle after birth (e.g. the let-7 and miR-15 families). Similar regulatory roles on CM proliferation are also exerted by a few Long ncRNAs. This body of information has obvious therapeutic implications, as miRNAs with activator function or short antisense oligonucleotides against inhibitory miRNAs or lncRNAs can be administered to stimulate cardiac regeneration. Expression of miRNAs can be achieved by gene therapy using adeno-associated vectors, which transduce CMs with high efficiency. More effective and safer for therapeutic purposes, small nucleic acid therapeutics can be obtained as chemically modified, synthetic molecules, which can be administered through lipofection or inclusion in lipid or polymer nanoparticles for efficient cardiac delivery. The notion that it is possible to reprogramme CMs into a regenerative state and that this property can be enhanced by ncRNA therapeutics remains exciting, however extensive experimentation in large mammals and rigorous assessment of safety are required to advance towards clinical application.
File in questo prodotto:
File Dimensione Formato  
Braga-2021.pdf

Accesso chiuso

Tipologia: Documento in Versione Editoriale
Licenza: Copyright Editore
Dimensione 1.36 MB
Formato Adobe PDF
1.36 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
cvaa071_supplementary_data.pdf

Accesso chiuso

Descrizione: Supplementary data
Tipologia: Altro materiale allegato
Licenza: Digital Rights Management non definito
Dimensione 27.23 kB
Formato Adobe PDF
27.23 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
Braga-2021-Post_print.pdf

Open Access dal 23/02/2022

Tipologia: Bozza finale post-referaggio (post-print)
Licenza: Digital Rights Management non definito
Dimensione 1.81 MB
Formato Adobe PDF
1.81 MB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11368/3051146
Citazioni
  • ???jsp.display-item.citation.pmc??? 37
  • Scopus 62
  • ???jsp.display-item.citation.isi??? 59
social impact