A peptide nucleic acid (PNA) masking the miR-145-5p binding site of the 3’UTR of the cystic fibrosis transmembrane conductance regulator (CFTR) mRNA enhances CFTR expression in Calu-3 cells

Shaiq Sultan, Andrea Rozzi, Jessica Gasparello, Alex Manicardi, Roberto Corradini, Chiara Papi, Alessia Finotti, Ilaria Lampronti, Eva Reali, Giulio Cabrini, Roberto Gambari, Monica Borgatti

Research output: Contribution to journalArticlepeer-review

Abstract

Peptide nucleic acids (PNAs) have been demonstrated to be very useful tools for gene regulation at different levels and with different mechanisms of action. In the last few years the use of PNAs for targeting microRNAs (anti-miRNA PNAs) has provided impressive advancements. In particular, targeting of microRNAs involved in the repression of the expression of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which is defective in cystic fibrosis (CF), is a key step in the development of new types of treatment protocols. In addition to the anti-miRNA therapeutic strategy, inhibition of miRNA functions can be reached by masking the miRNA binding sites present within the 3′UTR region of the target mRNAs. The objective of this study was to design a PNA masking the binding site of the microRNA miR-145-5p present within the 3′UTR of the CFTR mRNA and to determine its activity in inhibiting miR-145-5p function, with particular focus on the expression of both CFTR mRNA and CFTR protein in Calu-3 cells. The results obtained support the concept that the PNA masking the miR-145-5p binding site of the CFTR mRNA is able to interfere with miR-145-5p biological functions, leading to both an increase of CFTR mRNA and CFTR protein content.

Original languageEnglish
Article number1677
JournalMolecules
Volume25
Issue number7
DOIs
Publication statusPublished - 2020

Keywords

  • CFTR
  • Cystic fibrosis
  • Delivery
  • MicroRNAs
  • MiR-145-5p
  • MiRNA targeting
  • Peptide nucleic acids
  • PNA-masking

ASJC Scopus subject areas

  • Analytical Chemistry
  • Chemistry (miscellaneous)
  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery
  • Physical and Theoretical Chemistry
  • Organic Chemistry

Fingerprint Dive into the research topics of 'A peptide nucleic acid (PNA) masking the miR-145-5p binding site of the 3’UTR of the cystic fibrosis transmembrane conductance regulator (CFTR) mRNA enhances CFTR expression in Calu-3 cells'. Together they form a unique fingerprint.

Cite this