ArticleNature communications2015
Abasic pivot substitution harnesses target specificity of RNA interference.
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 35 papers.
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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.
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Who cites it
35 citing papers in PubMed, 52 citations in OpenAlex.
- RNA therapeutics: current status and future directions.Signal transduction and targeted therapy · 2026Review
- Dysregulated mScience advances · 2026Article
- abCRISPR: deep learning-based design of abasic gRNA sequences for specific CRISPR-Cas9 genome editing.Bioinformatics (Oxford, England) · 2026Article
- Acyclic serinol nucleic acid modification of siRNAs overcomes seed region mediated off-target effects while maintaining potency.Nucleic acids research · 2026Article
- Taming the Achilles' Heel: A Chemical and Structural Design to Address Off-Target Effects in siRNA Therapeutics.JACS Au · 2026Article
- Abasic CRISPR RNAs inherently harness fidelity of SpCas9 for genome editing.Nature chemical biology · 2026Article
- Knocking on Cells' Door: Strategic Approaches for miRNA and siRNA in Anticancer Therapy.International journal of molecular sciences · 2025Review
- Single alkyl phosphonate modification of the siRNA backbone in the seed region enhances specificity and therapeutic profile.Nucleic acids research · 2025Article
- Targeting CIDEB alleviates liver steatosis and fibrosis in mouse MASH models.Molecular therapy. Nucleic acids · 2025Article
- Chemical Modifications in Nucleic Acid Therapeutics.Methods in molecular biology (Clifton, N.J.) · 2025Review
- Synthesis of 2'-formamidonucleoside phosphoramidites for suppressing the seed-based off-target effects of siRNAs.Nucleic acids research · 2024Article
- Intracellular Protein Delivery: Approaches, Challenges, and Clinical Applications.BME frontiers · 2024Review
- Widespread 8-oxoguanine modifications of miRNA seeds differentially regulate redox-dependent cancer development.Nature cell biology · 2023Article
- Enhancing the Effectiveness of Oligonucleotide Therapeutics Using Cell-Penetrating Peptide Conjugation, Chemical Modification, and Carrier-Based Delivery Strategies.Pharmaceutics · 2023Review
- Engineering miRNA features into siRNAs: Guide-strand bulges are compatible with gene repression.Molecular therapy. Nucleic acids · 2022Article
- Overcoming GNA/RNA base-pairing limitations using isonucleotides improves the pharmacodynamic activity of ESC+ GalNAc-siRNAs.Nucleic acids research · 2021Article
- AGO CLIP-based imputation of potent siRNA sequences targeting SARS-CoV-2 with antifibrotic miRNA-like activity.Scientific reports · 2021Article
- siRNAs containing 2'-fluorinated Northern-methanocarbacyclic (2'-F-NMC) nucleotides: in vitro and in vivo RNAi activity and inability of mitochondrial polymerases to incorporate 2'-F-NMC NTPs.Nucleic acids research · 2021Article
- AGO-accessible anticancer siRNAs designed with synergistic miRNA-like activity.Molecular therapy. Nucleic acids · 2021Article
- Effective tools for RNA-derived therapeutics: siRNA interference or miRNA mimicry.Theranostics · 2021Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gene silencing via RNA interference inadvertently represses hundreds of off-target transcripts. Because small interfering RNAs (siRNAs) can function as microRNAs, avoiding miRNA-like off-target repression is a major challenge. Functional miRNA-target interactions are known to pre-require transitional nucleation, base pairs from position 2 to the pivot (position 6). Here, by substituting nucleotide in pivot with abasic spacers, which prevent base pairing and alleviate steric hindrance, we eliminate miRNA-like off-target repression while preserving on-target activity at ∼ 80-100%. Specifically, miR-124 containing dSpacer pivot substitution (6pi) loses seed-mediated transcriptome-wide target interactions, repression activity and biological function, whereas other conventional modifications are ineffective. Application of 6pi allows PCSK9 siRNA to efficiently lower plasma cholesterol concentration in vivo, and abolish potentially deleterious off-target phenotypes. The smallest spacer, C3, also shows the same improvement in target specificity. Abasic pivot substitution serves as a general means to harness the specificity of siRNA experiments and therapeutic applications.
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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.