Bioconjugation of small Molecules to rna impedes its recognition by Toll- like receptor 7
- Publikationstyp:
- Zeitschriftenaufsatz
- Metadaten:
-
- Autoren
- Isabell Hellmuth
- Isabel Freund
- Janine Schloeder
- Salifu Seidu-Larry
- Kathrin Thuering
- Kaouthar Slama
- Jens Langhanki
- Stefka Kaloyanova
- Tatjana Eigenbrod
- Matthias Krumb
- Sandra Roehm
- Kalina Peneva
- Till Opatz
- Helmut Jonuleit
- Alexander H Dalpke
- Mark Helm
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000397327300001&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.3389/fimmu.2017.00312
- Externe Identifier
- Clarivate Analytics Document Solution ID: EP4CD
- PubMed Identifier: 28392787
- ISSN
- 1664-3224
- Zeitschrift
- FRONTIERS IN IMMUNOLOGY
- Schlüsselwörter
- bioconjugate
- click chemistry
- immunostimulation
- mRNA
- siRNA
- small molecules
- toll-like receptorIN
- Artikelnummer
- ARTN 312
- Datum der Veröffentlichung
- 2017
- Status
- Published
- Titel
- Bioconjugation of small Molecules to rna impedes its recognition by Toll- like receptor 7
- Sub types
- Article
- Ausgabe der Zeitschrift
- 8
Datenquelle: Web of Science (Lite)
- Andere Metadatenquellen:
-
- Autoren
- Isabell Hellmuth
- Isabel Freund
- Janine Schlöder
- Salifu Seidu-Larry
- Kathrin Thüring
- Kaouthar Slama
- Jens Langhanki
- Stefka Kaloyanova
- Tatjana Eigenbrod
- Matthias Krumb
- Sandra Röhm
- Kalina Peneva
- Till Opatz
- Helmut Jonuleit
- Alexander H Dalpke
- Mark Helm
- DOI
- 10.3389/fimmu.2017.00312
- eISSN
- 1664-3224
- Zeitschrift
- Frontiers in Immunology
- Online publication date
- 2017
- Status
- Published online
- Herausgeber
- Frontiers Media SA
- Herausgeber URL
- http://dx.doi.org/10.3389/fimmu.2017.00312
- Datum der Datenerfassung
- 2022
- Titel
- Bioconjugation of Small Molecules to RNA Impedes Its Recognition by Toll-Like Receptor 7
- Ausgabe der Zeitschrift
- 8
Datenquelle: Crossref
- Abstract
- A fundamental mechanism of the innate immune system is the recognition, <i>via</i> extra- and intracellular pattern-recognition receptors, of pathogen-associated molecular patterns. A prominent example is represented by foreign nucleic acids, triggering the activation of several signaling pathways. Among these, the endosomal toll-like receptor 7 (TLR7) is known to be activated by single-stranded RNA (ssRNA), which can be specifically influenced through elements of sequence structure and posttranscriptional modifications. Furthermore, small molecules TLR7 agonists (smTLRa) are applied as boosting adjuvants in vaccination processes. In this context, covalent conjugations between adjuvant and vaccines have been reported to exhibit synergistic effects. Here, we describe a concept to chemically combine three therapeutic functions in one RNA bioconjugate. This consists in the simultaneous TLR7 stimulation by ssRNA and smTLRa as well as the therapeutic function of the RNA itself, e.g., as a vaccinating or knockdown agent. We have hence synthesized bioconjugates of mRNA and siRNA containing covalently attached smTLRa and tested their function in TLR7 stimulation. Strikingly, the bioconjugates displayed decreased rather than synergistically increased stimulation. The decrease was distinct from the antagonistic action of an siRNA bearing a Gm motive, as observed by direct comparison of the effects in the presence of otherwise stimulatory RNA. In summary, these investigations showed that TRL7 activation can be impeded by bioconjugation of small molecules to RNA.
- Addresses
- Institute of Pharmacy and Biochemistry, Johannes Gutenberg-University Mainz , Mainz , Germany.
- Autoren
- Isabell Hellmuth
- Isabel Freund
- Janine Schlöder
- Salifu Seidu-Larry
- Kathrin Thüring
- Kaouthar Slama
- Jens Langhanki
- Stefka Kaloyanova
- Tatjana Eigenbrod
- Matthias Krumb
- Sandra Röhm
- Kalina Peneva
- Till Opatz
- Helmut Jonuleit
- Alexander H Dalpke
- Mark Helm
- DOI
- 10.3389/fimmu.2017.00312
- eISSN
- 1664-3224
- Externe Identifier
- PubMed Identifier: 28392787
- PubMed Central ID: PMC5364167
- Funding acknowledgements
- Deutsche Forschungsgemeinschaft: SFB1066, Project B7, SFB1066, Project A2, He3397/9-1, Da592/5-1
- Open access
- true
- ISSN
- 1664-3224
- Zeitschrift
- Frontiers in immunology
- Sprache
- eng
- Medium
- Electronic-eCollection
- Online publication date
- 2017
- Open access status
- Open Access
- Paginierung
- 312
- Datum der Veröffentlichung
- 2017
- Status
- Published
- Publisher licence
- CC BY
- Datum der Datenerfassung
- 2017
- Titel
- Bioconjugation of Small Molecules to RNA Impedes Its Recognition by Toll-Like Receptor 7.
- Sub types
- research-article
- Journal Article
- Ausgabe der Zeitschrift
- 8
Files
https://www.frontiersin.org/articles/10.3389/fimmu.2017.00312/pdf https://europepmc.org/articles/PMC5364167?pdf=render
Datenquelle: Europe PubMed Central
- Abstract
- A fundamental mechanism of the innate immune system is the recognition, via extra- and intracellular pattern-recognition receptors, of pathogen-associated molecular patterns. A prominent example is represented by foreign nucleic acids, triggering the activation of several signaling pathways. Among these, the endosomal toll-like receptor 7 (TLR7) is known to be activated by single-stranded RNA (ssRNA), which can be specifically influenced through elements of sequence structure and posttranscriptional modifications. Furthermore, small molecules TLR7 agonists (smTLRa) are applied as boosting adjuvants in vaccination processes. In this context, covalent conjugations between adjuvant and vaccines have been reported to exhibit synergistic effects. Here, we describe a concept to chemically combine three therapeutic functions in one RNA bioconjugate. This consists in the simultaneous TLR7 stimulation by ssRNA and smTLRa as well as the therapeutic function of the RNA itself, e.g., as a vaccinating or knockdown agent. We have hence synthesized bioconjugates of mRNA and siRNA containing covalently attached smTLRa and tested their function in TLR7 stimulation. Strikingly, the bioconjugates displayed decreased rather than synergistically increased stimulation. The decrease was distinct from the antagonistic action of an siRNA bearing a Gm motive, as observed by direct comparison of the effects in the presence of otherwise stimulatory RNA. In summary, these investigations showed that TRL7 activation can be impeded by bioconjugation of small molecules to RNA.
- Date of acceptance
- 2017
- Autoren
- Isabell Hellmuth
- Isabel Freund
- Janine Schlöder
- Salifu Seidu-Larry
- Kathrin Thüring
- Kaouthar Slama
- Jens Langhanki
- Stefka Kaloyanova
- Tatjana Eigenbrod
- Matthias Krumb
- Sandra Röhm
- Kalina Peneva
- Till Opatz
- Helmut Jonuleit
- Alexander H Dalpke
- Mark Helm
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/28392787
- DOI
- 10.3389/fimmu.2017.00312
- Externe Identifier
- PubMed Central ID: PMC5364167
- ISSN
- 1664-3224
- Zeitschrift
- Front Immunol
- Schlüsselwörter
- bioconjugate
- click chemistry
- immunostimulation
- mRNA
- siRNA
- small molecules
- toll-like receptor
- Sprache
- eng
- Country
- Switzerland
- Paginierung
- 312
- Datum der Veröffentlichung
- 2017
- Status
- Published online
- Titel
- Bioconjugation of Small Molecules to RNA Impedes Its Recognition by Toll-Like Receptor 7.
- Sub types
- Journal Article
- Ausgabe der Zeitschrift
- 8
Datenquelle: PubMed
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