ArticleJournal of the American Chemical Society2016
Structure-Guided Control of siRNA Off-Target Effects.
Article in Journal of the American Chemical Society, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 42 citations in OpenAlex.
- Amide Internucleoside Linkages Suppress the MicroRNA-like Off-Target Activity of Short Interfering RNA.ACS chemical biology · 2025Article
- Synthesis of 2'-formamidonucleoside phosphoramidites for suppressing the seed-based off-target effects of siRNAs.Nucleic acids research · 2024Article
- Synthesis and Properties of RNA Modified with Thioamide Internucleoside Linkage.Chembiochem : a European journal of chemical biology · 2024Article
- Delivery Strategies of siRNA Therapeutics for Hair Loss Therapy.International journal of molecular sciences · 2024Review
- Synthesis and Properties of RNA Modified with Cationic Amine Internucleoside Linkage.ACS chemical biology · 2024Article
- Intracellular Protein Delivery: Approaches, Challenges, and Clinical Applications.BME frontiers · 2024Review
- Amide Modifications in the Seed Region of the Guide Strand Improve the On-Target Specificity of Short Interfering RNA.ACS chemical biology · 2023Article
- Delivering the Promise of Gene Therapy with Nanomedicines in Treating Central Nervous System Diseases.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Review
- siRNA potency enhancement via chemical modifications of nucleotide bases at the 5'-end of the siRNA guide strand.RNA (New York, N.Y.) · 2021Article
- Amide-Modified RNA: Using Protein Backbone to Modulate Function of Short Interfering RNAs.Accounts of chemical research · 2020Article
- Investigation of Strand-Selective Interaction of SNA-Modified siRNA with AGO2-MID.International journal of molecular sciences · 2020Article
- COPB2 promotes metastasis and inhibits apoptosis of lung adenocarcinoma cells through functioning as a target of miR-216a-3p.Translational cancer research · 2020Article
- Design, synthesis and evaluation of novel, branched trident small interfering RNA nanostructures for sequence-specific RNAi activity.RSC advances · 2019Article
- A Bump-Hole Approach for Directed RNA Editing.Cell chemical biology · 2019Article
- A Single Amide Linkage in the Passenger Strand Suppresses Its Activity and Enhances Guide Strand Targeting of siRNAs.ACS chemical biology · 2018Article
- Evaluation and control of miRNA-like off-target repression for RNA interference.Cellular and molecular life sciences : CMLS · 2018Review
- Exploring PAZ/3'-overhang interaction to improve siRNA specificity. A combined experimental and modeling study.Chemical science · 2018Article
- Fundamentals of siRNA and miRNA therapeutics and a review of targeted nanoparticle delivery systems in breast cancer.Biophysical reviews · 2018Review
- While it is not deliberate, much of today's biomedical research contains logical and technical flaws, showing a need for corrective action.International journal of medical sciences · 2018Review
- Controlling miRNA-like off-target effects of an siRNA with nucleobase modifications.Organic & biomolecular chemistry · 2017Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Short interfering RNAs (siRNAs) are promising therapeutics that make use of the RNA interference (RNAi) pathway, but liabilities arising from the native RNA structure necessitate chemical modification for drug development. Advances in the structural characterization of components of the human RNAi pathway have enabled structure-guided optimization of siRNA properties. Here we report the 2.3 Å resolution crystal structure of human Argonaute 2 (hAgo2), a key nuclease in the RNAi pathway, bound to an siRNA guide strand bearing an unnatural triazolyl nucleotide at position 1 (g1). Unlike natural nucleotides, this analogue inserts deeply into hAgo2's central RNA binding cleft and thus is able to modulate pairing between guide and target RNAs. The affinity of the hAgo2-siRNA complex for a seed-only matched target was significantly reduced by the triazolyl modification, while the affinity for a fully matched target was unchanged. In addition, siRNA potency for off-target repression was reduced (4-fold increase in IC50) by the modification, while on-target knockdown was improved (2-fold reduction in IC50). Controlling siRNA on-target versus microRNA (miRNA)-like off-target potency by projection of substituent groups into the hAgo2 central cleft from g1 is a new approach to enhance siRNA selectivity with a strong structural rationale.
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What OpenQuestion holds
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.