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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
Nov 30, 2023 Vol.46 No.11, pp. 655~725
COVER PICTURE
Kim et al. (pp. 710-724) demonstrated that a pathogen-derived Ralstonia pseudosolanacearum type III effector RipL delays flowering time and enhances susceptibility to bacterial infection in Arabidopsis thaliana. Shown is the RipL-expressing Arabidopsis plant, which displays general dampening of the transcriptional program during pathogen infection, grown in long-day conditions.

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