Gene Modulation by Peptide Nucleic Acids (PNAs) Targeting microRNAs (miRs)

Marchelli, Rosangela; Corradini, Roberto; Manicardi, Alex; Sforza, Stefano; Tedeschi, Tullia; Fabbri, Enrica; Borgatti, Monica; Bianchi, Nicoletta; Gambari, Roberto

doi:10.5772/21081

Cited by 10 publications

(8 citation statements)

References 90 publications

(59 reference statements)

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“…This was obtained in the absence of any transfection reagents, since the PNA was linked to a cell-penetrating peptide, R6-penetratin. In a second study, a PNA against miRNA-155 was used, demonstrating deregulation of the target mRNA Bat5 (2.7-fold increase of mRNA in PNA-treated cells), Sfp1 (2.7-fold Adapted from Marchelli et al [17].…”

Section: Biological Effects Of Treatment Of Target Cells With Anti-mimentioning

confidence: 99%

“…The first objective of this strategy is to obtain PNAs with both peptide properties and RNA binding ability, allowing a further improvement of the efficiency of PNA in miRNA targeting [17]. In this respect, the use of peptides as carriers represents a possible problem of the potential PNA-based drug candidates, since the peptide part might be subjected to enzymatic degradation; the incorporation of the positive-charged peptides within the PNA backbone (and not at C-or N-terminus) does not lead to enzymatic degradation, even in the presence of highly active proteases [17].…”

Section: Future Perspectivementioning

confidence: 99%

“…In addition to promoter, mRNA and protein targeting, PNAs have recently been reported as reagents that are able to strongly affect biological activity of miRNAs [11][12][13][14]. In view of the important biological role of miRNAs [15][16][17][18][19][20][21], PNAs can be proposed as possible miRNA modulators. This article focuses on the identification of the parameters affecting the ability of PNAs in regulating miRNA activity as well as the possible applications of anti-miRNA PNAs to control the expression of miRNA-regulated genes.…”

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confidence: 99%

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miRNA Therapeutics: Delivery and Biological Activity of Peptide Nucleic Acids Targeting miRNAs

et al. 2011

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Peptide nucleic acids (PNAs) are DNA/RNA mimics extensively used for pharmacological regulation of gene expression in a variety of cellular and molecular systems, and they have been described as excellent candidates for antisense and antigene therapies. At present, very few data are available on the use of PNAs as molecules targeting miRNAs. miRNAs are a family of small nc RNAs that regulate gene expression by sequence-selective targeting of mRNAs, leading to a translational repression or mRNA degradation to the control of highly regulated biological functions, such as differentiation, cell cycle and apoptosis. The aim of this article is to present the state-of-the-art concerning the possible use of PNAs to target miRNAs and modify their biological metabolism within the cells. The results present in the literature allow to propose PNA-based molecules as very promising reagents to modulate the biological activity of miRNAs. In consideration of the involvement of miRNAs in human pathologies, PNA-mediated targeting of miRNAs has been proposed as a potential novel therapeutic approach.

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Section: Biological Effects Of Treatment Of Target Cells With Anti-mimentioning

confidence: 99%

Section: Future Perspectivementioning

confidence: 99%

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confidence: 99%

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miRNA Therapeutics: Delivery and Biological Activity of Peptide Nucleic Acids Targeting miRNAs

et al. 2011

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“…Since their discovery as structural DNA analogs containing an uncharged N-(2-aminoethyl) glycine-based pseudopeptide backbone and mimicking DNA by forming Watson–Crick complementary duplexes with normal DNA [ 34 , 35 ], charge-neutral peptide nucleic acids (PNAs) have demonstrated tremendous potential for antigene and antisense therapy, functional genomics, or as a probe, useful in the toolbox for diagnosis and detection [ 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 ], and constitute an excellent model substrate for devising innovative approaches directed at nucleic acids’ primary structure reading.…”

Section: Introductionmentioning

confidence: 99%

The Nanopore-Tweezing-Based, Targeted Detection of Nucleobases on Short Functionalized Peptide Nucleic Acid Sequences

et al. 2021

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The implication of nanopores as versatile components in dedicated biosensors, nanoreactors, or miniaturized sequencers has considerably advanced single-molecule investigative science in a wide range of disciplines, ranging from molecular medicine and nanoscale chemistry to biophysics and ecology. Here, we employed the nanopore tweezing technique to capture amino acid-functionalized peptide nucleic acids (PNAs) with α-hemolysin-based nanopores and correlated the ensuing stochastic fluctuations of the ionic current through the nanopore with the composition and order of bases in the PNAs primary structure. We demonstrated that while the system enables the detection of distinct bases on homopolymeric PNA or triplet bases on heteropolymeric strands, it also reveals rich insights into the conformational dynamics of the entrapped PNA within the nanopore, relevant for perfecting the recognition capability of single-molecule sequencing.

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“…Though there are some of the disadvantages with unmodified PNA regarding cellular uptake, covalent coupling of PNA is required with cell penetrating peptides which improves cytosolic delivery. Artificial PNA oligomers which generally require 20-25 bases oligonucleotide probes have been used frequently in diagnosis, molecular biology procedures, antigene and antisense therapies (Marchelli et al, 2011). PNA is neither a nucleic acid nor a protein and it can withstand both nucleases and proteases; so has become a potential biomolecular tool with a superior lifetime for in vivo and in vitro applications such as, molecular diagnostics and antisense therapeutics (Janson and During, 2006).…”

Section: Introductionmentioning

confidence: 99%

Peptide nucleic acids: Advanced tools for biomedical applications

Gupta

Mishra

Puri³

2017

Journal of Biotechnology

143

120

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Peptide Nucleic Acids (PNAs) are the DNA/RNA analogues in which sugar-phosphate backbone is replaced by N-2-aminoethylglycine repeating units. PNA contains neutral backbone hence due to the absence of electrostatic repulsion, its hybridization shows remarkable stability towards complementary oligonucleotides. PNAs are highly resistant to cleavage by chemicals and enzymes due to the substrate specific nature of enzymes and therefore not degraded inside the cells. PNAs are emerging as new tools in the market due to their applications in antisense and antigene therapies by inhibiting translation and transcription respectively. Hence, several methods based on PNAs have been developed for designing various anticancer and antigene drugs, detection of mutations or modulation of PCR reactions. The duplex homopurine sequence of DNA may also be recognized by PNA, forming firm PNA/DNA/PNA triplex through strand invasion with a looped-out DNA strand. PNAs have also been found to replace DNA probes in varied investigative purposes. There are several disadvantages regarding cellular uptake of PNA, so modifications in PNA backbone or covalent coupling with cell penetrating peptides is necessary to improve its delivery inside the cells. In this review, hybridization properties along with potential applications of PNA in the field of diagnostics and pharmaceuticals are elaborated.

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Gene Modulation by Peptide Nucleic Acids (PNAs) Targeting microRNAs (miRs)

Cited by 10 publications

References 90 publications

miRNA Therapeutics: Delivery and Biological Activity of Peptide Nucleic Acids Targeting miRNAs

miRNA Therapeutics: Delivery and Biological Activity of Peptide Nucleic Acids Targeting miRNAs

The Nanopore-Tweezing-Based, Targeted Detection of Nucleobases on Short Functionalized Peptide Nucleic Acid Sequences

Peptide nucleic acids: Advanced tools for biomedical applications

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