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https://doi.org/10.1186/1471-2172-10-40
Title: | Sequence determinants of innate immune activation by short interfering RNAs | Authors: | Goodchild, A Nopper, N King, A Doan, T Tanudji, M Arndt, G.M Poidinger, M Rivory, L.P Passioura, T |
Keywords: | 1,2 dioleoyl 3 trimethylammoniopropane alpha interferon luciferase small interfering RNA toll like receptor 7 toll like receptor 8 toll like receptor 7 toll like receptor 8 tumor necrosis factor alpha uridine article controlled study cytokine production cytokine release endosome human human cell hybridization immunostimulation innate immunity nucleic acid base substitution peripheral blood mononuclear cell protein RNA binding RNA sequence thermodynamics biosynthesis chemistry dendritic cell drug effect drug potentiation immunology metabolism mononuclear cell tumor cell line Cell Line, Tumor Dendritic Cells Humans Immunity, Innate Leukocytes, Mononuclear RNA, Small Interfering Toll-Like Receptor 7 Toll-Like Receptor 8 Tumor Necrosis Factor-alpha Uridine |
Issue Date: | 2009 | Citation: | Goodchild, A, Nopper, N, King, A, Doan, T, Tanudji, M, Arndt, G.M, Poidinger, M, Rivory, L.P, Passioura, T (2009). Sequence determinants of innate immune activation by short interfering RNAs. BMC Immunology 10 : 40. ScholarBank@NUS Repository. https://doi.org/10.1186/1471-2172-10-40 | Rights: | Attribution 4.0 International | Abstract: | Background: Short 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. Results: A 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. Conclusion: The 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. © 2009 Goodchild et al; licensee BioMed Central Ltd. | Source Title: | BMC Immunology | URI: | https://scholarbank.nus.edu.sg/handle/10635/177950 | ISSN: | 14712172 | DOI: | 10.1186/1471-2172-10-40 | Rights: | Attribution 4.0 International |
Appears in Collections: | Elements Staff Publications |
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