ArticleChembiochem : a European journal of chemical biology2015
Base modification strategies to modulate immune stimulation by an siRNA.
Article in Chembiochem : a European journal of chemical biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
16 citing papers in PubMed, 30 citations in OpenAlex.
- Small Interfering RNA Carriers for Oncotherapy: A Preclinical Overview.Pharmaceutics · 2025Review
- Knocking on Cells' Door: Strategic Approaches for miRNA and siRNA in Anticancer Therapy.International journal of molecular sciences · 2025Review
- The Progress and Evolving Trends in Nucleic-Acid-Based Therapies.Biomolecules · 2025Review
- Small nucleic acid drugs-the dawn of functional cure of chronic hepatitis B.Frontiers in pharmacology · 2025Review
- RNA Interference Therapeutics for Chronic Hepatitis B: Progress, Challenges, and Future Prospects.Microorganisms · 2024Review
- Small interfering RNA (siRNA)-based therapeutic applications against viruses: principles, potential, and challenges.Journal of biomedical science · 2023Review
- A holistic analysis of the intrinsic and delivery-mediated toxicity of siRNA therapeutics.Advanced drug delivery reviews · 2023Review
- Advances in modification and delivery of nucleic acid drugs.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2023Review
- Therapeutic siRNA: State-of-the-Art and Future Perspectives.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2022Review
- Therapeutic siRNA: state of the art.Signal transduction and targeted therapy · 2020Review
- Nucleotide Modifications Decrease Innate Immune Response Induced by Synthetic Analogs of snRNAs and snoRNAs.Genes · 2018Article
- RNA interference-based therapy and its delivery systems.Cancer metastasis reviews · 2018Review
- TLR8 activation and inhibition by guanosine analogs in RNA: Importance of functional groups and chain length.Bioorganic & medicinal chemistry · 2018Article
- Article
- Progress and Prospects of Anti-HBV Gene Therapy Development.International journal of molecular sciences · 2015Review
- Safety of Striatal Infusion of siRNA in a Transgenic Huntington's Disease Mouse Model.Journal of Huntington's disease · 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
6 authors at 1 institution in 1 country.
Funding
Abstract
Immune stimulation triggered by siRNAs is one of the major challenges in the development of safe RNAi-based therapeutics. Within an immunostimulatory siRNA sequence, this hurdle is commonly addressed by using ribose modifications (e.g., 2'-OMe or 2'-F), which results in decreased cytokine production. However, as immune stimulation by siRNAs is a sequence-dependent phenomenon, recognition of the nucleobases by the trigger receptor(s) is also likely. Here, we use the recently published crystal structures of Toll-like receptor 8 (TLR8) bound to small-molecule agonists to generate computational models for ribonucleotide binding by this immune receptor. Our modeling suggested that modification of either the Watson-Crick or Hoogsteen face of adenosine would disrupt nucleotide/TLR8 interactions. We employed chemical synthesis to alter either the Watson-Crick or Hoogsteen face of adenosine and evaluated the effect of these modifications in an siRNA guide strand by measuring the immunostimulatory and RNA interference properties. For the siRNA guide strand tested, we found that modifying the Watson-Crick face is generally more effective at blocking TNFα production in human peripheral blood mononuclear cells (PBMCs) than modification at the Hoogsteen edge. We also observed that modifications near the 5'-end were more effective at blocking cytokine production than those placed at the 3'-end. This work advances our understanding of how chemical modifications can be used to optimize siRNA performance.
Indexed as
Identifiers
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.