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Peptide Nucleic Acids as miRNA Target Protectors for the Treatment of Cystic Fibrosis
by
Borbone, Nicola
, Oliviero, Giorgia
, Amato, Felice
, Santarpia, Giuliano
, D’Errico, Stefano
, Piccialli, Gennaro
, Zarrilli, Federica
, Morgillo, Carmine Marco
, Catalanotti, Bruno
, Pinto, Brunella
, Castaldo, Giuseppe
in
3' Untranslated Regions - genetics
/ A549 Cells
/ CFTR
/ Cystic fibrosis
/ Cystic Fibrosis - genetics
/ Cystic Fibrosis - therapy
/ Cystic Fibrosis Transmembrane Conductance Regulator - antagonists & inhibitors
/ Cystic Fibrosis Transmembrane Conductance Regulator - genetics
/ Humans
/ MicroRNAs - antagonists & inhibitors
/ MicroRNAs - genetics
/ miR-509-3p
/ miRNA
/ miRNA target protectors
/ Mutation
/ peptide nucleic acid
/ Peptide Nucleic Acids - genetics
/ Peptide Nucleic Acids - therapeutic use
/ PNA
/ RNA, Messenger - genetics
/ Transfection
2017
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Peptide Nucleic Acids as miRNA Target Protectors for the Treatment of Cystic Fibrosis
by
Borbone, Nicola
, Oliviero, Giorgia
, Amato, Felice
, Santarpia, Giuliano
, D’Errico, Stefano
, Piccialli, Gennaro
, Zarrilli, Federica
, Morgillo, Carmine Marco
, Catalanotti, Bruno
, Pinto, Brunella
, Castaldo, Giuseppe
in
3' Untranslated Regions - genetics
/ A549 Cells
/ CFTR
/ Cystic fibrosis
/ Cystic Fibrosis - genetics
/ Cystic Fibrosis - therapy
/ Cystic Fibrosis Transmembrane Conductance Regulator - antagonists & inhibitors
/ Cystic Fibrosis Transmembrane Conductance Regulator - genetics
/ Humans
/ MicroRNAs - antagonists & inhibitors
/ MicroRNAs - genetics
/ miR-509-3p
/ miRNA
/ miRNA target protectors
/ Mutation
/ peptide nucleic acid
/ Peptide Nucleic Acids - genetics
/ Peptide Nucleic Acids - therapeutic use
/ PNA
/ RNA, Messenger - genetics
/ Transfection
2017
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Peptide Nucleic Acids as miRNA Target Protectors for the Treatment of Cystic Fibrosis
by
Borbone, Nicola
, Oliviero, Giorgia
, Amato, Felice
, Santarpia, Giuliano
, D’Errico, Stefano
, Piccialli, Gennaro
, Zarrilli, Federica
, Morgillo, Carmine Marco
, Catalanotti, Bruno
, Pinto, Brunella
, Castaldo, Giuseppe
in
3' Untranslated Regions - genetics
/ A549 Cells
/ CFTR
/ Cystic fibrosis
/ Cystic Fibrosis - genetics
/ Cystic Fibrosis - therapy
/ Cystic Fibrosis Transmembrane Conductance Regulator - antagonists & inhibitors
/ Cystic Fibrosis Transmembrane Conductance Regulator - genetics
/ Humans
/ MicroRNAs - antagonists & inhibitors
/ MicroRNAs - genetics
/ miR-509-3p
/ miRNA
/ miRNA target protectors
/ Mutation
/ peptide nucleic acid
/ Peptide Nucleic Acids - genetics
/ Peptide Nucleic Acids - therapeutic use
/ PNA
/ RNA, Messenger - genetics
/ Transfection
2017
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Peptide Nucleic Acids as miRNA Target Protectors for the Treatment of Cystic Fibrosis
Journal Article
Peptide Nucleic Acids as miRNA Target Protectors for the Treatment of Cystic Fibrosis
2017
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Overview
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.
Publisher
MDPI AG,MDPI
Subject
3' Untranslated Regions - genetics
/ CFTR
/ Cystic Fibrosis Transmembrane Conductance Regulator - antagonists & inhibitors
/ Cystic Fibrosis Transmembrane Conductance Regulator - genetics
/ Humans
/ MicroRNAs - antagonists & inhibitors
/ miRNA
/ Mutation
/ Peptide Nucleic Acids - genetics
/ Peptide Nucleic Acids - therapeutic use
/ PNA
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