ArticleNucleic acids research2005
A systematic analysis of the silencing effects of an active siRNA at all single-nucleotide mismatched target sites.
Article in Nucleic acids research, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 117 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.
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Who cites it
117 citing papers in PubMed, 268 citations in OpenAlex.
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- Specificity of DNA targeting by RNA-guided pAgo nucleases.Nucleic acids research · 2026Article
- HDAC6 Inhibition Reduces Seeded Tau and α-Synuclein Pathologies in Primary Neuron Cultures and Wild-Type Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- RNAi-mediated gene silencing of a 26S proteasome subunit increases mortality of the Japanese beetle Popillia japonica.Pest management science · 2026Article
- Synthetic short RNA in cancer.Frontiers in oncology · 2026Review
- Ribosomal RNA-Specific Antisense DNA and Double-Stranded DNA Trigger rRNA Biogenesis and Insecticidal Effects on the Insect PestInternational journal of molecular sciences · 2025Article
- RNAi Strategies Against Downy Mildews: Insights Into dsRNA Uptake and Silencing.Molecular plant pathology · 2025Article
- Review
- Therapeutic Approaches of Viral Gene Silencing by Small Interfering RNA: Strategies to Prevent the Emergence of Antiviral Resistant Escape Mutants.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Optimizing dsRNA sequences for RNAi in pest control and research with the dsRIP web platform.BMC biology · 2025Article
- Alterations of mRNAs and Non-coding RNAs Associated with Neuroinflammation in Alzheimer's Disease.Molecular neurobiology · 2024Review
- Optimized allele-specific silencing of the dominant-negativeMolecular therapy. Nucleic acids · 2024Article
- The 'genetic zipper' method offers a cost-effective solution for aphid control.Frontiers in insect science · 2024Article
- Putative Core Transcription Factors Affecting Virulence inJournal of fungi (Basel, Switzerland) · 2023Article
- Allele-specific silencing by RNAi of R92Q and R173W mutations in cardiac troponin T.Experimental biology and medicine (Maywood, N.J.) · 2022Article
- Engineering miRNA features into siRNAs: Guide-strand bulges are compatible with gene repression.Molecular therapy. Nucleic acids · 2022Article
- SARS-CoV-2 expresses a microRNA-like small RNA able to selectively repress host genes.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Emergent RNA-RNA interactions can promote stability in a facultative phototrophic endosymbiosis.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- DNAzyme Cleavage of CAG Repeat RNA in Polyglutamine Diseases.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Article
57 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The specificity of small interfering RNA (siRNA)-mediated gene silencing is a critical consideration for the application of RNA interference (RNAi). While the discovery of potential off-target effects by siRNAs is of concern, no systematic analysis has been conducted to explore the specificity of RNAi. Here, we present a study where a functionally validated siRNA (siCD46) was examined for silencing specificity on all possible 57 permutated target sites, each carrying a single-nucleotide mutation that would generate a mismatch when paired with siRNA antisense strand. We found that it was not only the position of the mismatched base pair, but also the identity of the nucleotides forming the mismatch that influenced silencing. Surprisingly, mismatches formed between adenine (A) and cytosine (C), in addition to the G:U wobble base pair, were well tolerated and target sites containing such mismatches were silenced almost as efficiently as its fully matched counterpart by siCD46. Northern blots showed that the silencing of fusion genes harboring the mutated target sites involved target mRNA degradation. This study provides direct evidence that the target recognition of siRNA is far more degenerative than previously considered. This finding is instrumental in the understanding of RNAi specificity and may aid the computational prediction of RNA secondary structure.
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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.