ArticleNature communications2022
An LNA-amide modification that enhances the cell uptake and activity of phosphorothioate exon-skipping oligonucleotides.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
25 citing papers in PubMed, 39 citations in OpenAlex.
- 5'-Palmitate Lipid and Internal LNA-Piperidyl Triesters Enhance the RNA Affinity and Activity of Splice-Switching Oligonucleotides.Journal of the American Chemical Society · 2026Article
- RNA-based precision medicine in glioblastoma driven by oncogenic gene fusions.Molecular therapy. Oncology · 2026Review
- RNA-Based Therapies for Inherited Metabolic Disorders.Journal of inherited metabolic disease · 2026Review
- Genetic therapies for neurological diseases.Pharmacological reviews · 2026Review
- Biophysical and biological properties of splice-switching oligonucleotides and click conjugates containing LNA-phosphothiotriester linkages.Nucleic acids research · 2025Article
- Synthesis, Biological Activity, and Molecular Dynamics Simulations of LNA-Charge Neutral Linkages for Enhanced Splice-Switching Antisense Oligonucleotides.Angewandte Chemie (International ed. in English) · 2025Article
- From liquid-phase synthesis to chemical ligation: preparation of oligonucleotides and their backbone analogs in solution.Nucleic acids research · 2025Review
- Targeting intestinal inflammation using locked nucleic acids delivered via lipid nanoparticles.Nature communications · 2025Article
- Effect of chemical modification on the exon-skipping activity of heteroduplex oligonucleotides.Molecular therapy. Nucleic acids · 2025Article
- Landscape of small nucleic acid therapeutics: moving from the bench to the clinic as next-generation medicines.Signal transduction and targeted therapy · 2025Review
- WhenFrontiers in pharmacology · 2025Article
- Engineering Considerations for Developing Next-Generation Oligonucleotide Therapeutics.Nature chemical engineering · 2024Article
- Synthesis, Biophysical and Biological Evaluation of Splice-Switching Oligonucleotides with Multiple LNA-Phosphothiotriester Backbones.Journal of the American Chemical Society · 2024Article
- 2'-ACS medicinal chemistry letters · 2024Article
- A Visual Compendium of Principal Modifications within the Nucleic Acid Sugar Phosphate Backbone.Molecules (Basel, Switzerland) · 2024Review
- Unlocking the therapeutic potential of locked nucleic acids through lipid nanoparticle delivery.Molecular therapy. Nucleic acids · 2024Review
- Synthesis and Properties of Oligonucleotides Containing LNA-Sulfamate and Sulfamide Backbone Linkages.Organic letters · 2024Article
- Synthesis and Properties of RNA Modified with Cationic Amine Internucleoside Linkage.ACS chemical biology · 2024Article
- Influence of Combinations of Lipophilic and Phosphate Backbone Modifications on Cellular Uptake of Modified Oligonucleotides.Molecules (Basel, Switzerland) · 2024Article
- A non-lipid nucleic acid delivery vector with dendritic cell tropism and stimulation.Theranostics · 2024Article
Corrections and comments
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Authors and funding
18 authors at 5 institutions in 3 countries.
Funding
Abstract
Oligonucleotides that target mRNA have great promise as therapeutic agents for life-threatening conditions but suffer from poor bioavailability, hence high cost. As currently untreatable diseases come within the reach of oligonucleotide therapies, new analogues are urgently needed to address this. With this in mind we describe reduced-charge oligonucleotides containing artificial LNA-amide linkages with improved gymnotic cell uptake, RNA affinity, stability and potency. To construct such oligonucleotides, five LNA-amide monomers (A, T, C, 5mC and G), where the 3'-OH is replaced by an ethanoic acid group, are synthesised in good yield and used in solid-phase oligonucleotide synthesis to form amide linkages with high efficiency. The artificial backbone causes minimal structural deviation to the DNA:RNA duplex. These studies indicate that splice-switching oligonucleotides containing LNA-amide linkages and phosphorothioates display improved activity relative to oligonucleotides lacking amides, highlighting the therapeutic potential of this technology.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.