ArticleNucleic acids research2020
In vitro and in vivo properties of therapeutic oligonucleotides containing non-chiral 3' and 5' thiophosphate linkages.
Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Photocatalytic synthesis of phosphorothioates by sulfur transfer from thiosulfate.Chemical science · 2026Article
- TRNAU1AP and PRPF39 establish integrated control over processing of most abundant human non-coding RNAs.Nature communications · 2026Article
- Silver nanoparticle-induced site-specific strand cleavage of chemically modified oligonucleotides for long-chain DNA assembly.Nucleic acids research · 2026Article
- The efficacy of oligonucleotide-based gene therapeutics in gene silencing.Theranostics · 2026Review
- Effective treatment of systemic candidiasis by synergistic targeting of cell wall synthesis.Nature communications · 2025Article
- A Visual Compendium of Principal Modifications within the Nucleic Acid Sugar Phosphate Backbone.Molecules (Basel, Switzerland) · 2024Review
- Locked Nucleic Acid Oligonucleotides Facilitate RNA•LNA-RNA Triple-Helix Formation and ReduceInternational journal of molecular sciences · 2024Article
- Photoinduced Synthesis of Sulfonyl-Containing Phosphorothioates via a Three-Component Reaction.Molecules (Basel, Switzerland) · 2023Article
- Photochemical halogen-bonding assisted carbothiophosphorylation reactions of alkenyl and 1,3-dienyl bromides.Chemical science · 2023Article
- Smad7 Antisense Oligonucleotide in Crohn's Disease: A Re-Evaluation and Explanation for the Discordant Results of Clinical Trials.Pharmaceutics · 2022Article
- Investigating discovery strategies and pharmacological properties of stereodefined phosphorodithioate LNA gapmers.Molecular therapy. Nucleic acids · 2022Article
- Chemically Modified Poly(A) Analogs Targeting PABP: Structure Activity Relationship and Translation Inhibitory Properties.Chemistry (Weinheim an der Bergstrasse, Germany) · 2022Article
- Lipid nanoparticles for antisense oligonucleotide gene interference into brain border-associated macrophages.Frontiers in molecular biosciences · 2022Article
- Delivery of therapeutic oligonucleotides in nanoscale.Bioactive materials · 2022Review
- A Multifunctional LNA Oligonucleotide-Based Strategy Blocks AR Expression and Transactivation Activity in PCa Cells.Molecular therapy. Nucleic acids · 2021Article
- Modified internucleoside linkages for nuclease-resistant oligonucleotides.RSC chemical biology · 2021Review
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Authors and funding
10 authors.
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No grant is acknowledged in the PubMed record.
Abstract
The introduction of non-bridging phosphorothioate (PS) linkages in oligonucleotides has been instrumental for the development of RNA therapeutics and antisense oligonucleotides. This modification offers significantly increased metabolic stability as well as improved pharmacokinetic properties. However, due to the chiral nature of the phosphorothioate, every PS group doubles the amount of possible stereoisomers. Thus PS oligonucleotides are generally obtained as an inseparable mixture of a multitude of diastereoisomeric compounds. Herein, we describe the introduction of non-chiral 3' thiophosphate linkages into antisense oligonucleotides and report their in vitro as well as in vivo activity. The obtained results are carefully investigated for the individual parameters contributing to antisense activity of 3' and 5' thiophosphate modified oligonucleotides (target binding, RNase H recruitment, nuclease stability). We conclude that nuclease stability is the major challenge for this approach. These results highlight the importance of selecting meaningful in vitro experiments particularly when examining hitherto unexplored chemical modifications.
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