ArticleMolecular therapy : the journal of the American Society of Gene Therapy2010
Rational design of immunostimulatory siRNAs.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 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
38 citing papers in PubMed, 77 citations in OpenAlex.
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- Autologous platelet delivery of siRNAs by autologous plasma protein self-assembled nanoparticles for the treatment of acute kidney injury.Journal of nanobiotechnology · 2025Article
- Therapeutic efficacy of a novel self-assembled immunostimulatory siRNA combining apoptosis promotion with RIG-I activation in gliomas.Journal of translational medicine · 2024Article
- Innate immune regulations and various siRNA modalities.Drug delivery and translational research · 2023Review
- Pharmacological inhibition of TBK1/IKKε blunts immunopathology in a murine model of SARS-CoV-2 infection.Nature communications · 2023Article
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- Immunostimulatory siRNA with a uridine bulge leads to potent inhibition of HBV and activation of innate immunity.Virology journal · 2021Article
- Anti-tumor efficacy of plasmid encoding emm55 in a murine melanoma model.Cancer immunology, immunotherapy : CII · 2020Article
- Rational design of antisense oligonucleotides modulating the activity of TLR7/8 agonists.Nucleic acids research · 2020Article
- Review
- Apoptotic endothelial cells release small extracellular vesicles loaded with immunostimulatory viral-like RNAs.Scientific reports · 2019Article
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- Advancement of the Emerging Field of RNA Nanotechnology.ACS nano · 2017Review
- RNA Interference-Induced Innate Immunity, Off-Target Effect, or Immune Adjuvant?Frontiers in immunology · 2017Review
- Development of Novel Small Hairpin RNAs That do not Require Processing by Dicer or AGO2.Molecular therapy : the journal of the American Society of Gene Therapy · 2016Article
- Toll-Like Receptor 7-Targeted Therapy in Respiratory Disease.Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie · 2016Review
- Prediction of Immunomodulatory potential of an RNA sequence for designing non-toxic siRNAs and RNA-based vaccine adjuvants.Scientific reports · 2016Article
Corrections and comments
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Authors and funding
9 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Short-interfering RNAs (siRNAs) have engendered much enthusiasm for their ability to silence the expression of specific genes. However, it is now well established that siRNAs, depending on their sequence, can be variably sensed by the innate immune system through recruitment of toll-like receptors 7 and 8 (TLR7/8). Here, we aimed to identify sequence-based modifications allowing for the design of bifunctional siRNAs with both proinflammatory and specific silencing activities, and with potentially increased therapeutic benefits. We found that the introduction of a micro-RNA (miRNA)-like nonpairing uridine-bulge in the passenger strand robustly increased immunostimulatory activity on human immune cells. This sequence modification had no effect on the silencing efficiency of the siRNA. Increased immunostimulation with the uridine-bulge design was specific to human cells, and conserved silencing efficiency required a Dicer-substrate scaffold. The increased cytokine production with the uridine-bulge design resulted in enhanced protection against Semliki Forest virus (SFV) infection, in viral assays. Thus, we characterize a design scaffold applicable to any given siRNA sequence, that results in increased innate immune activation without affecting gene silencing. Our data suggest that this sequence modification coupled with structural modification differentially recruits human TLR8 over TLR7, and could have potential application in antiviral therapies.
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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.