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LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00004043naa a2200673 4500
001oai:openarchive.ki.se:10616/48411
003SwePub
008240410s2021 | |||||||||||000 ||eng|
009oai:prod.swepub.kib.ki.se:147830459
022 a 2157-846X
024a 10616/484112 hdl
024a http://hdl.handle.net/10616/484112 URI
024a https://doi.org/10.1038/s41551-021-00792-z2 DOI
024a http://kipublications.ki.se/Default.aspx?queryparsed=id:1478304592 URI
040 a (SwePub)ki
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
100a Gupta, Dhanuu Karolinska Institutet4 aut
2451 0a Amelioration of systemic inflammation via the display of two different decoy protein receptors on extracellular vesicles
264 c 2021-10-06
264 1a Stockholm :b Karolinska Institutet, Dept of Laboratory Medicine,c 2021
338 a electronic2 rdacarrier
520 a 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.
700a Wiklander, Oscar P Bu Karolinska Institutet4 aut
700a Görgens, Andréu Karolinska Institutet4 aut
700a Conceição, Mariana4 aut
700a Corso, Giuliau Karolinska Institutet4 aut
700a Liang, Xiumingu Karolinska Institutet4 aut
700a Seow, Yiqi4 aut
700a Balusu, Sriram4 aut
700a Feldin, Ulrika4 aut
700a Bostancioglu, Beklem4 aut
700a Jawad, Rimu Karolinska Institutet4 aut
700a Mamand, Doste Ru Karolinska Institutet4 aut
700a Lee, Yi Xin Fiona4 aut
700a Hean, Justin4 aut
700a Mäger, Imre4 aut
700a Roberts, Thomas C4 aut
700a Gustafsson, Manuelau Karolinska Institutet4 aut
700a Mohammad, Dara Ku Karolinska Institutet4 aut
700a Sork, Helenau Karolinska Institutet4 aut
700a Backlund, Alexandra4 aut
700a Lundin, Per4 aut
700a de Fougerolles, Antonin4 aut
700a Smith, C I Edvardu Karolinska Institutet4 aut
700a Wood, Matthew J A4 aut
700a Vandenbroucke, Roosmarijn E4 aut
700a Nordin, Joel Zu Karolinska Institutet4 aut
700a El-Andaloussi, Samiru Karolinska Institutet4 aut
710a Karolinska Institutet
710a Karolinska Institutet
710a Karolinska Institutet4 org
773t Nature Biomedical Engineeringd Stockholm : Karolinska Institutet, Dept of Laboratory Medicinex 2157-846X
856u http://hdl.handle.net/10616/48411x primaryx Object in contextx freey FULLTEXT
8564 8u http://hdl.handle.net/10616/48411
8564 8u https://doi.org/10.1038/s41551-021-00792-z
8564 8u http://kipublications.ki.se/Default.aspx?queryparsed=id:147830459

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