ArticleChembiochem : a European journal of chemical biology2016
Guide Strand 3'-End Modifications Regulate siRNA Specificity.
Article in Chembiochem : a European journal of chemical biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 16 citations in OpenAlex.
- Presence of phosphodiester backbone, but not nucleobases, in the guide's 3' terminal region is necessary for RISC loading and target cleavage in vitro and in vivo.Nucleic acids research · 2026Article
- Clickable RNA via 4'-Bioconjugate chemistry · 2025Article
- Role of ncRNAs in the Development of Chronic Pain.Non-coding RNA · 2025Review
- 2'-O-Methyl at 20-mer Guide Strand 3' Termini May Negatively Affect Target Silencing Activity of Fully Chemically Modified siRNA.Molecular therapy. Nucleic acids · 2020Article
- A Unique Gene-Silencing Approach, Using an Intelligent RNA Expression Device (iRed), Results in Minimal Immune Stimulation When Given by Local Intrapleural Injection in Malignant Pleural Mesothelioma.Molecules (Basel, Switzerland) · 2020Article
- Comparison of thermally actuated retro-diels-alder release groups for nanoparticle based nucleic acid delivery.Journal of colloid and interface science · 2018Article
- Article
- Exploring PAZ/3'-overhang interaction to improve siRNA specificity. A combined experimental and modeling study.Chemical science · 2018Article
- Site-Specific Modification Using the 2'-Methoxyethyl Group Improves the Specificity and Activity of siRNAs.Molecular therapy. Nucleic acids · 2017Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Short interfering RNA (siRNA)-triggered gene knockdown through the RNA interference (RNAi) pathway is widely used to study gene function, and siRNA-based therapeutics are in development. However, as the guide strand of an siRNA can function like a natural microRNA (miRNA), siRNAs often repress hundreds of off-target transcripts with complementarity only to the seed region (nucleotides 2-8) of the guide strand. Here, we describe novel guide strand 3'-end modifications derived from 1-ethynylribose (1-ER) and copper-catalyzed azide-alkyne cycloaddition reactions and evaluate their impact on target versus miRNA-like off-target knockdown. Surprisingly, when positioned at the guide strand 3'-end, the parent 1-ER modification substantially reduced off-target knockdown while having no measurable effect on on-target knockdown potency. In addition, these modifications were shown to modulate siRNA affinity for the hAgo2 PAZ domain. However, the change in PAZ domain binding affinity was not sufficient to predict the modification's effect on miRNA-like off targeting.
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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.