ArticleBMC immunology2009
Sequence determinants of innate immune activation by short interfering RNAs.
Article in BMC immunology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.
- RNA Drugs and RNA Targets for Small Molecules: Principles, Progress, and Challenges.Pharmacological reviews · 2020Pooled it
- Safety and Pharmacokinetics of SRN001, a Novel siRNA Drug Targeting Amphiregulin via the SAMiRNA Platform.Drug design, development and therapy · 2026Trial
- Multi-Omics-Guided Design and Safety Engineering of Nucleic Acid Therapeutics: From Molecular Perturbation to Predictive Toxicology and Precision Translation.Chemical biology & drug design · 2026Review
- Long Non-Coding RNAs in HER2-Positive Breast Cancer: From Resistance Mechanisms to Translational Potential.Oncology research · 2026Review
- Nucleic acid therapeutics in neurodegenerative disorders: emerging technologies and clinical landscape.Molecular neurodegeneration advances · 2026Review
- RNA-DNA Differences: Mechanisms, Oxidative Stress, Transcriptional Fidelity, and Health Implications.Antioxidants (Basel, Switzerland) · 2025Review
- The Impact of Chemical Modifications on the Interferon-Inducing and Antiproliferative Activity of Short Double-Stranded Immunostimulating RNA.Molecules (Basel, Switzerland) · 2024Article
- Principle, application and challenges of development siRNA-based therapeutics against bacterial and viral infections: a comprehensive review.Frontiers in microbiology · 2024Review
- A holistic analysis of the intrinsic and delivery-mediated toxicity of siRNA therapeutics.Advanced drug delivery reviews · 2023Review
- Lipid-based nucleic acid therapeutics with in vivo efficacy.Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology · 2023Review
- Article
- Self-delivering RNAi compounds as therapeutic agents in the central nervous system to enhance axonal regeneration after injury.iScience · 2022Article
- Therapeutic RNA interference: A novel approach to the treatment of primary hyperoxaluria.British journal of clinical pharmacology · 2022Review
- Intratracheal Administration of siRNA Triggers mRNA Silencing in the Lung to Modulate T Cell Immune Response and Lung Inflammation.Molecular therapy. Nucleic acids · 2019Article
- Editorial focus: understanding off-target effects as the key to successful RNAi therapy.Cellular & molecular biology letters · 2019Review
- Transforming growth factor β1 (TGFβ1) regulates CD44V6 expression and activity through extracellular signal-regulated kinase (ERK)-induced EGR1 in pulmonary fibrogenic fibroblasts.The Journal of biological chemistry · 2017Article
- Imaging-guided delivery of RNAi for anticancer treatment.Advanced drug delivery reviews · 2016Review
- Prediction of Immunomodulatory potential of an RNA sequence for designing non-toxic siRNAs and RNA-based vaccine adjuvants.Scientific reports · 2016Article
- siRNA Versus miRNA as Therapeutics for Gene Silencing.Molecular therapy. Nucleic acids · 2015Review
- Short-interference RNAs: becoming medicines.EXCLI journal · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundShort interfering RNAs (siRNAs) have been shown to induce immune stimulation through a number of different receptors in a range of cell types. In primary cells, both TLR7 and TLR8 have been shown to recognise siRNAs however, despite the identification of a number of TLR7/8 stimulatory RNA motifs, the complete and definitive sequence determinants of TLR7 and TLR8 are yet to be elucidated.
resultsA total of 207 siRNA sequences were screened for TLR7/8 stimulation in human PBMCs. There was a significant correlation between the U count of the U-rich strand and the immunostimulatory activity of the duplex. Using siRNAs specifically designed to analyse the effect of base substitutions and hybridisation of the two strands, we found that sequence motifs and the thermodynamic properties of the duplexes appeared to be the major determinants of siRNA immunogenicity and that the strength of the hybridisation interaction between the two strands correlated negatively with immunostimulatory activity.
conclusionThe data presented favour a model of TLR7/8 activation by siRNAs, in which the two strands are denatured in the endosome, and single-stranded, U-rich RNA species activate TLR7/8. These findings have relevance to the design of siRNAs, particularly for in vivo or clinical 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.