Researchers synthesized PNAs targeting the 3’UTR of CFTR, EZR and NHERF1 mRNAs. They demonstrated that PNAs specific for miR-145-5p and miR-101-3p inhibit miR-145-5p and miR-101-3p biological activity and increase CFTR mRNA content (RT-qPCR) and CFTR protein production (Western blotting) by cystic fibrosis Calu-3 cells. They found that a PNA targeting miR-335-5p (specific for NHERF1 3’UTR sequence) inhibits miR-335-5p and induces NHERF1 production (Western blotting). At the same time, it is able to increase CFTR (Western blotting) and CFTR function in the FRT-YFP F508del CFTR cells. The potency of this effect was similar to VX809. All the employed PNAs were not toxic, did not induce inhibition of cell growth and activation of apoptosis. This pilot project gave evidence that PNA-based targeting of miRNAs regulating CFTR and players of the CFTR interactome could implement mutated CFTR rescue.