ArticleProceedings of the National Academy of Sciences of the United States of America2007
Stabilized immune modulatory RNA compounds as agonists of Toll-like receptors 7 and 8.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. 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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Who cites it
35 citing papers in PubMed, 74 citations in OpenAlex.
- Advanced technologies for the development of infectious disease vaccines.Nature reviews. Drug discovery · 2024Review
- Dichotomous roles of RIPK3 in regulating the IFN response and NLRP3 inflammasome in human monocytes.Journal of leukocyte biology · 2023Article
- An Overview of the Use of Nanoparticles in Vaccine Development.Nanomaterials (Basel, Switzerland) · 2023Review
- Application of toll-like receptors (TLRs) and their agonists in cancer vaccines and immunotherapy.Frontiers in immunology · 2023Review
- CXCL4 synergizes with TLR8 for TBK1-IRF5 activation, epigenomic remodeling and inflammatory response in human monocytes.Nature communications · 2022Article
- Structural evolution of toll-like receptor 7/8 agonists from imidazoquinolines to imidazoles.RSC medicinal chemistry · 2021Review
- Unc-13 homolog D mediates an antiviral effect of the chromosome 19 microRNA cluster miR-517a.Journal of cell science · 2020Article
- Agonist and antagonist ligands of toll-like receptors 7 and 8: Ingenious tools for therapeutic purposes.European journal of medicinal chemistry · 2020Review
- Review
- Intratumoural immunotherapy: activation of nucleic acid sensing pattern recognition receptors.Immuno-oncology technology · 2019Review
- RNA-Based Immunostimulatory Liposomal Spherical Nucleic Acids as Potent TLR7/8 Modulators.Small (Weinheim an der Bergstrasse, Germany) · 2018Article
- Small-Molecule TLR8 Antagonists via Structure-Based Rational Design.Cell chemical biology · 2018Article
- TLR8 activation and inhibition by guanosine analogs in RNA: Importance of functional groups and chain length.Bioorganic & medicinal chemistry · 2018Article
- Targeting of Immune Cells by Dual TLR2/7 Ligands Suppresses Features of Allergic Th2 Immune Responses in Mice.Journal of immunology research · 2017Article
- RAGE Enhances TLR Responses through Binding and Internalization of RNA.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- Costimulatory and coinhibitory immune checkpoint receptors in head and neck cancer: unleashing immune responses through therapeutic combinations.Cancers of the head & neck · 2016Review
- Inhibition of indoleamine 2,3-dioxygenase activity enhances the anti-tumour effects of a Toll-like receptor 7 agonist in an established cancer model.Immunology · 2015Article
- Cutting edge: the UNC93B1 tyrosine-based motif regulates trafficking and TLR responses via separate mechanisms.Journal of immunology (Baltimore, Md. : 1950) · 2014Article
- The Yin and Yang of Toll-like receptors in cancer.Oncogene · 2014Review
- In vitro inflammation inhibition model based on semi-continuous toll-like receptor biosensing.PloS one · 2014Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Viral and synthetic single-stranded RNAs are the ligands for Toll-like receptor (TLR)7 and TLR8. However, single-stranded RNA is rapidly degraded by ubiquitous RNases, and the studies reported to date have used RNA with lipid carriers. To overcome nuclease susceptibility of RNA, we have synthesized several RNAs incorporating a range of chemical modifications. The present study describes one pool of RNA compounds, referred to as stabilized immune modulatory RNA (SIMRA) compounds, in which two RNA segments are attached through their 3' ends. SIMRA compounds showed greater stability in human serum compared with linear RNA and activated human TLR8, but not TLR7, in HEK293 cells without using lipid carriers. Interestingly, another set of SIMRA compounds containing 7-deazaguanosine substituted for natural guanosine activated human TLR7 and TLR8. Additionally, TLR7- and TLR8-activating compounds, but not the compounds that activated only TLR8, stimulated mouse immune cells in vitro and in vivo and produced dose-dependent T helper 1-type cytokines. Both types of compounds activated human peripheral blood mononuclear cells, but only TLR7- and TLR8-activating compounds activated plasmacytoid dendritic cells and produced high levels of IFN-alpha. In monkeys, s.c. administration of both types of SIMRA compounds induced transient changes in peripheral blood monocytes and neutrophils, and activated T lymphocytes, monocytes, and NK cells. Both types of compounds induced IFN-gamma-inducible protein 10, but only the 7-deazaguanosine-containing compound that activated both TLR7 and TLR8 induced IFN-alpha in monkeys. This is a comprehensive study of RNA-based compounds containing structures and synthetic stimulatory motifs in mouse, monkey, and human systems without using lipid carriers.
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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.