ArticleInternational journal of molecular sciences2022
Identification of an Optimal TLR8 Ligand by Alternating the Position of 2'-O-Ribose Methylation.
Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- A comprehensive analysis of the use of nucleoside analogues in RNA therapeutics.Journal of translational medicine · 2026Review
- Nucleotide modifications enable rational design of TLR7-selective ligands by blocking RNase cleavage.The Journal of experimental medicine · 2024Article
- The Role of Toll-like Receptors (TLRs) and Their Related Signaling Pathways in Viral Infection and Inflammation.International journal of molecular sciences · 2023Article
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7 authors.
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Abstract
Recognition of RNA by receptors of the innate immune system is regulated by various posttranslational modifications. Different single 2'-O-ribose (2'-O-) methylations have been shown to convert TLR7/TLR8 ligands into specific TLR8 ligands, so we investigated whether the position of 2'-O-methylation is crucial for its function. To this end, we designed different 2'-O-methylated RNA oligoribonucleotides (ORN), investigating their immune activity in various cell systems and analyzing degradation under RNase T2 treatment. We found that the 18S rRNA-derived TLR7/8 ligand, RNA63, was differentially digested as a result of 2'-O-methylation, leading to variations in TLR8 and TLR7 inhibition. The suitability of certain 2'-O-methylated RNA63 derivatives as TLR8 agonists was further demonstrated by the fact that other RNA sequences were only weak TLR8 agonists. We were thus able to identify specific 2'-O-methylated RNA derivatives as optimal TLR8 ligands.
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