miRNA Therapeutics: Delivery and Biological Activity of Peptide Nucleic Acids Targeting miRNAs

Abstract

Peptide nucleic acids (PNAs) are DNA/RNA mimics extensively used for pharmacological regulation of gene expression in a variety of cellular and molecular systems, and they have been described as excellent candidates for antisense and antigene therapies. At present, very few data are available on the use of PNAs as molecules targeting miRNAs. miRNAs are a family of small nc RNAs that regulate gene expression by sequence-selective targeting of mRNAs, leading to a translational repression or mRNA degradation to the control of highly regulated biological functions, such as differentiation, cell cycle and apoptosis. The aim of this article is to present the state-of-the-art concerning the possible use of PNAs to target miRNAs and modify their biological metabolism within the cells. The results present in the literature allow to propose PNA-based molecules as very promising reagents to modulate the biological activity of miRNAs. In consideration of the involvement of miRNAs in human pathologies, PNA-mediated targeting of miRNAs has been proposed as a potential novel therapeutic approach.

KEYWORDS::

• epigenetics
• gene regulation
• gene transcription
• miRNAs
• peptide nucleic acids

Acknowledgements

The authors thank M Ferracin and M Negrini (Department of Experimental and Diagnostic Medicine, Ferrara University, Italy) for helpful suggestions.

Financial&competing interests disclosure

This work was supported by a grant by MIUR (Italian Ministry of University and Research). R Gambari is granted by Fondazione Cariparo (Cassa di Risparmio di Padova e Rovigo), CIB, by UE ITHANET Project (eInfrastructure for the Thalassaemia Research Network), by Telethon GGP10124 and by FIRB-2007. This research is also supported by Associazione Veneta per la Lotta alla Talassemia (AVLT), Rovigo. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This work was supported by a grant by MIUR (Italian Ministry of University and Research). R Gambari is granted by Fondazione Cariparo (Cassa di Risparmio di Padova e Rovigo), CIB, by UE ITHANET Project (eInfrastructure for the Thalassaemia Research Network), by Telethon GGP10124 and by FIRB-2007. This research is also supported by Associazione Veneta per la Lotta alla Talassemia (AVLT), Rovigo. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.