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Mol. Cells 2009; 28(4): 341-345

Published online September 30, 2009

https://doi.org/10.1007/s10059-009-0134-8

© The Korean Society for Molecular and Cellular Biology

A Highly Effective and Long-Lasting Inhibition of miRNAs with PNA-Based AntisenseOligonucleotides

Su Young Oh, YeongSoon Ju, and Heekyung Park
Ki-Woong Cho, and Yup Kang

Received: April 28, 2009; Revised: August 18, 2009; Accepted: August 26, 2009

Abstract

MiRNAs are non-coding RNAs that play a role in the regulation of major processes. The inhibition of miRNAs using antisense oligonucleotides (ASOs) is a unique and effective technique for the characterization and subsequent therapeutic targeting of miRNA function. Recent advances in ASO chemistry have been used to increase both the resistance to nucleases and the target affinity and specificity of these ASOs.
Peptide nucleic acids (PNAs) are artificial oligonucleo-tides constructed on a peptide-like backbone. PNAs have a stronger affinity and greater specificity to DNA or RNA than natural nucleic acids and are resistant to nucleases, which is an essential characteristic for a miRNA inhibitor that will be exposed to serum and cellular nucleases.
For increasing cell penetration, PNAs were conjugated with cell penetrating peptides (CPPs) at N-terminal. Among the tested CPPs, Tat-modified peptide-conjugated PNAs have most effective function for miRNA inhibition. PNA-based ASO was more effective miRNA inhibitor than other DNA-based ASOs and did not show cytotoxicity at concentration up to 1,000 nM. The effects of PNA-based ASOs were shown to persist for 9 days. Also, PNA-based ASOs showed considerable stability at storage temperature. These results suggest that PNA-based ASOs are more effective ASOs of miRNA than DNA-based ASOs and PNA-based ASO technology, compared with other technologies used to inhibit miRNA activity can be an effective tool for investigating miRNA functions.

Keywords antisense oligonucleotides (ASOs), cell penetrating peptides (CPPs), microRNA (miRNA), peptide nucleic acids (PNAs), PNA-based ASO

Article

Research Article

Mol. Cells 2009; 28(4): 341-345

Published online October 31, 2009 https://doi.org/10.1007/s10059-009-0134-8

Copyright © The Korean Society for Molecular and Cellular Biology.

A Highly Effective and Long-Lasting Inhibition of miRNAs with PNA-Based AntisenseOligonucleotides

Su Young Oh, YeongSoon Ju, and Heekyung Park
Ki-Woong Cho, and Yup Kang

Received: April 28, 2009; Revised: August 18, 2009; Accepted: August 26, 2009

Abstract

MiRNAs are non-coding RNAs that play a role in the regulation of major processes. The inhibition of miRNAs using antisense oligonucleotides (ASOs) is a unique and effective technique for the characterization and subsequent therapeutic targeting of miRNA function. Recent advances in ASO chemistry have been used to increase both the resistance to nucleases and the target affinity and specificity of these ASOs.
Peptide nucleic acids (PNAs) are artificial oligonucleo-tides constructed on a peptide-like backbone. PNAs have a stronger affinity and greater specificity to DNA or RNA than natural nucleic acids and are resistant to nucleases, which is an essential characteristic for a miRNA inhibitor that will be exposed to serum and cellular nucleases.
For increasing cell penetration, PNAs were conjugated with cell penetrating peptides (CPPs) at N-terminal. Among the tested CPPs, Tat-modified peptide-conjugated PNAs have most effective function for miRNA inhibition. PNA-based ASO was more effective miRNA inhibitor than other DNA-based ASOs and did not show cytotoxicity at concentration up to 1,000 nM. The effects of PNA-based ASOs were shown to persist for 9 days. Also, PNA-based ASOs showed considerable stability at storage temperature. These results suggest that PNA-based ASOs are more effective ASOs of miRNA than DNA-based ASOs and PNA-based ASO technology, compared with other technologies used to inhibit miRNA activity can be an effective tool for investigating miRNA functions.

Keywords: antisense oligonucleotides (ASOs), cell penetrating peptides (CPPs), microRNA (miRNA), peptide nucleic acids (PNAs), PNA-based ASO

Mol. Cells
May 31, 2023 Vol.46 No.5, pp. 259~328
COVER PICTURE
The alpha-helices in the lamin filaments are depicted as coils, with different subdomains distinguished by various colors. Coil 1a is represented by magenta, coil 1b by yellow, L2 by green, coil 2a by white, coil 2b by brown, stutter by cyan, coil 2c by dark blue, and the lamin Ig-like domain by grey. In the background, cells are displayed, with the cytosol depicted in green and the nucleus in blue (Ahn et al., pp. 309-318).

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