ArticleNature communications2015
Stereochemical bias introduced during RNA synthesis modulates the activity of phosphorothioate siRNAs.
Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 92 citations in OpenAlex.
- Chalcogen-modified Nucleic Acid Analogues.Current medicinal chemistry · 2026Article
- Landscape of small nucleic acid therapeutics: moving from the bench to the clinic as next-generation medicines.Signal transduction and targeted therapy · 2025Review
- A Visual Compendium of Principal Modifications within the Nucleic Acid Sugar Phosphate Backbone.Molecules (Basel, Switzerland) · 2024Review
- RNAi-based drug design: considerations and future directions.Nature reviews. Drug discovery · 2024Review
- Targeting RNA with synthetic oligonucleotides: Clinical success invites new challenges.Cell chemical biology · 2024Review
- Macrophage polarization in spinal cord injury repair and the possible role of microRNAs: A review.Heliyon · 2023Review
- Impact of stereopure chimeric backbone chemistries on the potency and durability of gene silencing by RNA interference.Nucleic acids research · 2023Article
- Solid-phase synthesis and properties of stereocontrolled boranophosphate/phosphate and phosphorothioate/phosphate chimeric oligouridylates.Royal Society open science · 2023Article
- Future directions for medicinal chemistry in the field of oligonucleotide therapeutics.RNA (New York, N.Y.) · 2023Article
- Modified Nucleotides for Chemical and Enzymatic Synthesis of Therapeutic RNA.Current medicinal chemistry · 2023Article
- Pharmacological inhibition of Lin28 promotes ketogenesis and restores lipid homeostasis in models of non-alcoholic fatty liver disease.Nature communications · 2022Article
- Inhomogeneous Diastereomeric Composition of Mongersen Antisense Phosphorothioate Oligonucleotide Preparations and Related Pharmacological Activity Impairment.Nucleic acid therapeutics · 2022Article
- Inhaled siRNA Formulations for Respiratory Diseases: From Basic Research to Clinical Application.Pharmaceutics · 2022Review
- Chirality matters: stereo-defined phosphorothioate linkages at the termini of small interfering RNAs improve pharmacology in vivo.Nucleic acids research · 2022Article
- Nature Chose Phosphates and Chemists Should Too: How Emerging P(V) Methods Can Augment Existing Strategies.ACS central science · 2021Review
- A P(V) platform for oligonucleotide synthesis.Science (New York, N.Y.) · 2021Article
- Pharmacodynamic and Pharmacokinetic Properties of Full Phosphorothioate Small Interfering RNAs for Gene SilencingNucleic acid therapeutics · 2021Article
- Modified internucleoside linkages for nuclease-resistant oligonucleotides.RSC chemical biology · 2021Review
- Unresolved Issues in RNA Therapeutics in Vascular Diseases With a Focus on Aneurysm Disease.Frontiers in cardiovascular medicine · 2021Review
- Synthesis and properties of DNA oligomers containing stereopure phosphorothioate linkages and C-5 modified deoxyuridine derivatives.RSC advances · 2020Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
An established means of improving the pharmacokinetics properties of oligoribonucleotides (ORNs) is to exchange their phosphodiester linkages for phosphorothioates (PSs). However, this strategy has not been pursued for small interfering RNAs (siRNAs), possibly because of sporadic reports that PS siRNAs show reduced inhibitory activity. The PS group is chiral at phosphorous (Rp/Sp centres), and conventional solid-phase synthesis of PS ORNs produces a population of diastereoisomers. Here we show that the choice of the activating agent for the synthesis of a PS ORN influences the Rp/Sp ratio of PS linkages throughout the strand. Furthermore, PS siRNAs composed of ORNs with a higher fraction of Rp centres show greater resistance to nucleases in serum and are more effective inhibitors in cells than their Sp counterparts. The finding that a stereochemically biased population of ORN diastereoisomers can be synthesized and exploited pharmacologically is important because uniform PS modification of siRNAs may provide a useful compromise of their pharmacokinetics and pharmacodynamics properties in RNAi therapeutics.
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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.