Researchers designed and synthesized peptide nucleic acids (or PNAs) that are potentially therapeutic molecules for CF. PNAs are able to regulate the gene expression through the interaction with other key molecules of gene regulation, microRNA (or miRNA). The research team showed that in vitro, a PNA is able to interact with the “miRNA 145-5p” increasing the gene expression of CFTR and respective protein.
The researchers also report that the use of PNAs in addition to available modulators such as VX809 and VX770 increases the functionality of the CFTR protein. The specificity PNAs, which have been shown to be selective for the target miRNAs, is also demonstrated. The researchers also investigated the transport ofPNAs in the cells, so they characterized two delivery systems: one based on porous silicon nanoparticles and another based on a cyclic macromolecule. The analysis of the entire set of all cellular miRNAs (miRNome) of CF people, has shown a heterogeneity between individuals suggesting the importance of a personalized strategy for PNA/miRNAs therapy.

Pubblications

• Manicardi A, Gambari R, de Cola et al. Preparation of Anti-miR PNAs for Drug Development and Nanomedicine, Methods in MolBiol 2018;1811:49-63.
• Gasparello J, Lomazzi M, Papi C et al. Efficient delivery of MicroRNA and AntimiRNA molecules using an Argininocalix[4]arene macrocycle, Molecular Therapy – Nucleic Acids2019 Dec 6;18:748-763
• Finotti A, Fabbri E, Lampronti I et al. MicroRNAs and Long Non-coding RNAs in Genetic Diseases, Molecular Diagnosis & Therapy2019 Jan 4.
• Gasparello J, Manicardi A, Casnati A et al. Efficient cell penetration and delivery of peptide nucleic acids by an argininocalix[4]arene, Scientific Reports 2019 Feb 28;9(1):3036.
• Gambari R, Targeting microRNAs in Cystic Fibrosis (CF), International Journal of Molecular Medicine 44: supplement, 2019, page S22.
• Sultan S, Fabbri E, Tamanini A et al. A PNA-based masking strategy for CFTR upregulation by targeting miR-145-5p binding sites of CFTR mRNA, International Journal of Molecular Medicine44: supplement, 2019, page S22.
• Gambari R, Gasparello J, Fabbri E et al. Peptide Nucleic Acids for MicroRNA Targeting, Methods Mol Biol. 2020;2105:199-215.
• Cabrini G, Rimessi A, Borgatti M et al. Role of Cystic Fibrosis Bronchial Epithelium in Neutrophil Chemotaxis, Mucosal Immunology 2020 Aug 4;11:1438
• Sultan S, Rozzi A, Gasparello J et al. A Peptide Nucleic Acid (PNA) Masking the miR-145-5p Binding Site of the 30UTR of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) mRNA Enhances CFTR Expression in Calu-3 Cells, Molecules 2020 Apr 5;25(7):1677.
• Fabbri E, Tamanini A, Jakova T et al. Treatment of human airway epithelial Calu-3 cells with a peptide-nucleic acid (PNA) targeting the microRNA miR-101-3p is associated with increased expression of the cystic fibrosis Transmembrane Conductance Regulator () gene, European Journal of Medicinal Chemistry, 2 October 2020, 112876.
• Tamanini A, Fabbri E, Jakova T et al. A Peptide-Nucleic Acid Targeting miR-335-5p Enhances Expression of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Gene with the Possible Involvement of the CFTR Scaffolding Protein NHERF1, Biomedicines 2021 Jan 26;9(2):117.