ArticleNucleic acids research2022
Thyclotides, tetrahydrofuran-modified peptide nucleic acids that efficiently penetrate cells and inhibit microRNA-21.
Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 19 citations in OpenAlex.
- Design, Synthesis and Biophysical Characterisation of CPP-PNA Conjugates for Targeting Oncogenic microRNA-221.Journal of peptide science : an official publication of the European Peptide Society · 2026Article
- Multiple Charged Purine (MCP) PNA as a Simple Mode for Cellular Uptake.ACS polymers Au · 2026Article
- RNA detection on a microfluidic platform using Thyclotides.Sensors and actuators reports · 2026Article
- Article
- Tetrahydrofuran Peptide Nucleic Acids.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Enhancing diabetes treatment by targeted nucleic acid and drug delivery using cell-penetrating peptides, peptide nucleic acids, and receptor targeting.Frontiers in pharmacology · 2026Review
- Recent Cutting-Edge Technologies for the Delivery of Peptide Nucleic Acid.Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Review
- Mir-615-3p promotes osteosarcoma progression via the SESN2/AMPK/mTOR pathway.Cancer cell international · 2024Article
- Epigenetic frontiers: miRNAs, long non-coding RNAs and nanomaterials are pioneering to cancer therapy.Epigenetics & chromatin · 2024Review
- MicroRNAs in diabetic macroangiopathy.Cardiovascular diabetology · 2024Review
- Impact of charges on the hybridization kinetics and thermal stability of PNA duplexes.Organic & biomolecular chemistry · 2024Article
- Extracellular vesicles derived from human ESC-MSCs target macrophage and promote anti-inflammation process, angiogenesis, and functional recovery in ACS-induced severe skeletal muscle injury.Stem cell research & therapy · 2023Article
- Variation of Tetrahydrofurans in Thyclotides Enhances Oligonucleotide Binding and Cellular Uptake of Peptide Nucleic Acids.JACS Au · 2023Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Peptide nucleic acids (PNAs) are promising therapeutic molecules for gene modulation; however, they suffer from poor cell uptake. Delivery of PNAs into cells requires conjugation of the PNA to another large molecule, typically a cell-penetrating peptide or nanoparticle. In this study, we describe a new PNA-based molecule with cyclic tetrahydrofuran (THF) backbone modifications that in some cases considerably improve cell uptake. We refer to these THF-PNA oligomers as thyclotides. With THF groups at every position of the oligomer, the cell uptake of thyclotides targeted to miR-21 is enhanced compared with the corresponding unmodified PNA based on an aminoethylglycine backbone. An optimized thyclotide can efficiently enter cells without the use of cell-penetrating peptides, bind miR-21, its designated microRNA target, decrease expression of miR-21 and increase expression of three downstream targets (PTEN, Cdc25a and KRIT1). Using a plasmid with the PTEN-3'UTR coupled with luciferase, we further confirmed that a miR-21-targeted thyclotide prevents miR-21 from binding to its target RNA. Additionally, the thyclotide shows no cytotoxicity when administered at 200 times its active concentration. We propose that thyclotides be further explored as therapeutic candidates to modulate miRNA levels.
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