Peptide Nucleic Acids for MicroRNAs Targeting: Updates and Future Perspectives

The involvement of microRNAs in human pathologies is firmly established. Accordingly, the pharmacological modulation of microRNA activity appears to be a very interesting approach in the development of new types of drugs (miRNA Therapeutics). One important research area is the possible development of miRNA Therapeutics in the field of rare diseases. In this respect, appealing molecules are based on peptide nucleic acids (PNAs), displaying, in their first description, a pseudo-peptide backbone composed of N-(2-aminoethyl)glycine units and found to be excellent candidates for antisense and antigéne therapies. The aim of the present article is to describe methods for determining the activity of PNAs designed to inhibit the biological activity of microRNAs involved in Cystic Fibrosis, using as model system miR-145-5p and its target Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) mRNA. Antisense PNAs and miRNA masking PNAs were considered. The methods employed to study the effects of PNAs altering the biological activity of miR-145-5p are here presented discussing data obtained using as a cellular model system the human lung epithelial Calu-3 cell line.