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Molecules 2017, 22(7), 1144; doi:10.3390/molecules22071144

Peptide Nucleic Acids as miRNA Target Protectors for the Treatment of Cystic Fibrosis

1
Department of Biosciences and Territory, University of Molise, 86170 Isernia, Italy
2
CEINGE–Advanced Biotechnologies Scarl, 80131 Napoli, Italy
3
Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, 80131 Napoli, Italy
4
Department of Pharmacy, University of Naples Federico II, 80131 Napoli, Italy
*
Author to whom correspondence should be addressed.
Received: 31 May 2017 / Revised: 3 July 2017 / Accepted: 4 July 2017 / Published: 8 July 2017
(This article belongs to the Special Issue Molecular Properties and the Applications of Peptide Nucleic Acids)
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Abstract

Cystic Fibrosis (CF) is one of the most common life shortening conditions in Caucasians. CF is caused by mutations in the CF Transmembrane Conductance Regulator (CFTR) gene which result in reduced or altered CFTR functionality. Several microRNAs (miRNAs) downregulate the expression of CFTR, thus causing or exacerbating the symptoms of CF. In this context, the design of anti-miRNA agents represents a valid functional tool, but its translation to the clinic might lead to unpredictable side effects because of the interference with the expression of other genes regulated by the same miRNAs. Herein, for the first time, is proposed the use of peptide nucleic acids (PNAs) to protect specific sequences in the 3’UTR (untranslated region) of the CFTR messenger RNA (mRNA) by action of miRNAs. Two PNAs (7 and 13 bases long) carrying the tetrapeptide Gly-SerP-SerP-Gly at their C-end, fully complementary to the 3’UTR sequence recognized by miR-509-3p, have been synthesized and the structural features of target PNA/RNA heteroduplexes have been investigated by spectroscopic and molecular dynamics studies. The co-transfection of the pLuc-CFTR-3´UTR vector with different combinations of PNAs, miR-509-3p, and controls in A549 cells demonstrated the ability of the longer PNA to rescue the luciferase activity by up to 70% of the control, thus supporting the use of suitable PNAs to counteract the reduction in the CFTR expression. View Full-Text
Keywords: cystic fibrosis; CFTR; miRNA; miRNA target protectors; miR-509-3p; peptide nucleic acid; PNA cystic fibrosis; CFTR; miRNA; miRNA target protectors; miR-509-3p; peptide nucleic acid; PNA
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Zarrilli, F.; Amato, F.; Morgillo, C.M.; Pinto, B.; Santarpia, G.; Borbone, N.; D’Errico, S.; Catalanotti, B.; Piccialli, G.; Castaldo, G.; Oliviero, G. Peptide Nucleic Acids as miRNA Target Protectors for the Treatment of Cystic Fibrosis. Molecules 2017, 22, 1144.

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