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  • Gupta, DhanuKarolinska Institutet (author)

Amelioration of systemic inflammation via the display of two different decoy protein receptors on extracellular vesicles

  • Article/chapterEnglish2021

Publisher, publication year, extent ...

  • 2021-10-06
  • Stockholm :Karolinska Institutet, Dept of Laboratory Medicine,2021
  • electronicrdacarrier

Numbers

  • LIBRIS-ID:oai:openarchive.ki.se:10616/48411
  • ISSN:2157-846X
  • 10616/48411hdl
  • http://hdl.handle.net/10616/48411URI
  • https://doi.org/10.1038/s41551-021-00792-zDOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:147830459URI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Extracellular vesicles (EVs) can be functionalized to display specific protein receptors on their surface. However, surface-display technology typically labels only a small fraction of the EV population. Here, we show that the joint display of two different therapeutically relevant protein receptors on EVs can be optimized by systematically screening EV-loading protein moieties. We used cytokine-binding domains derived from tumour necrosis factor receptor 1 (TNFR1) and interleukin-6 signal transducer (IL-6ST), which can act as decoy receptors for the pro-inflammatory cytokines tumour necrosis factor alpha (TNF-α) and IL-6, respectively. We found that the genetic engineering of EV-producing cells to express oligomerized exosomal sorting domains and the N-terminal fragment of syntenin (a cytosolic adaptor of the single transmembrane domain protein syndecan) increased the display efficiency and inhibitory activity of TNFR1 and IL-6ST and facilitated their joint display on EVs. In mouse models of systemic inflammation, neuroinflammation and intestinal inflammation, EVs displaying the cytokine decoys ameliorated the disease phenotypes with higher efficacy as compared with clinically approved biopharmaceutical agents targeting the TNF-α and IL-6 pathways.

Added entries (persons, corporate bodies, meetings, titles ...)

  • Wiklander, Oscar P BKarolinska Institutet (author)
  • Görgens, AndréKarolinska Institutet (author)
  • Conceição, Mariana (author)
  • Corso, GiuliaKarolinska Institutet (author)
  • Liang, XiumingKarolinska Institutet (author)
  • Seow, Yiqi (author)
  • Balusu, Sriram (author)
  • Feldin, Ulrika (author)
  • Bostancioglu, Beklem (author)
  • Jawad, RimKarolinska Institutet (author)
  • Mamand, Doste RKarolinska Institutet (author)
  • Lee, Yi Xin Fiona (author)
  • Hean, Justin (author)
  • Mäger, Imre (author)
  • Roberts, Thomas C (author)
  • Gustafsson, ManuelaKarolinska Institutet (author)
  • Mohammad, Dara KKarolinska Institutet (author)
  • Sork, HelenaKarolinska Institutet (author)
  • Backlund, Alexandra (author)
  • Lundin, Per (author)
  • de Fougerolles, Antonin (author)
  • Smith, C I EdvardKarolinska Institutet (author)
  • Wood, Matthew J A (author)
  • Vandenbroucke, Roosmarijn E (author)
  • Nordin, Joel ZKarolinska Institutet (author)
  • El-Andaloussi, SamirKarolinska Institutet (author)
  • Karolinska Institutet
  • Karolinska Institutet
  • Karolinska Institutet (creator_code:org_t)

Related titles

  • In:Nature Biomedical EngineeringStockholm : Karolinska Institutet, Dept of Laboratory Medicine2157-846X

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