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Amelioration of systemic inflammation via the display of two different decoy protein receptors on extracellular vesicles.
Gupta, Dhanu; Wiklander, Oscar P B; Görgens, André; Conceição, Mariana; Corso, Giulia; Liang, Xiuming; Seow, Yiqi; Balusu, Sriram; Feldin, Ulrika; Bostancioglu, Beklem; Jawad, Rim; Mamand, Doste R; Lee, Yi Xin Fiona; Hean, Justin; Mäger, Imre; Roberts, Thomas C; Gustafsson, Manuela; Mohammad, Dara K; Sork, Helena; Backlund, Alexandra; Lundin, Per; de Fougerolles, Antonin; Smith, C I Edvard; Wood, Matthew J A; Vandenbroucke, Roosmarijn E; Nordin, Joel Z; El-Andaloussi, Samir.
Afiliación
  • Gupta D; Biomolecular Medicine, Clinical Research Center, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden. dhanu.gupta@ki.se.
  • Wiklander OPB; Biomolecular Medicine, Clinical Research Center, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden. oscar.wiklander@ki.se.
  • Görgens A; Biomolecular Medicine, Clinical Research Center, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Conceição M; Institute for Transfusion Medicine, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
  • Corso G; Department of Paediatrics, University of Oxford, Oxford, UK.
  • Liang X; Biomolecular Medicine, Clinical Research Center, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Seow Y; Biomolecular Medicine, Clinical Research Center, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Balusu S; Molecular Engineering Laboratory, Institute for Bioengineering and Nanotechnology, A*STAR, Singapore, Singapore.
  • Feldin U; VIB Center for Inflammation Research, VIB, Ghent, Belgium.
  • Bostancioglu B; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
  • Jawad R; Biomolecular Medicine, Clinical Research Center, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Mamand DR; Biomolecular Medicine, Clinical Research Center, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Lee YXF; Biomolecular Medicine, Clinical Research Center, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Hean J; Biomolecular Medicine, Clinical Research Center, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Mäger I; Biology Department, Cihan University-Erbil, Erbil, Iraq.
  • Roberts TC; Biomolecular Medicine, Clinical Research Center, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Gustafsson M; Genome Institute of Singapore, Agency for Science, Technology and Research, A*STAR, Singapore, Singapore.
  • Mohammad DK; Evox Therapeutics Limited, Oxford, UK.
  • Sork H; Department of Paediatrics, University of Oxford, Oxford, UK.
  • Backlund A; Department of Paediatrics, University of Oxford, Oxford, UK.
  • Lundin P; MDUK Oxford Neuromuscular Centre, University of Oxford, Oxford, UK.
  • de Fougerolles A; Biomolecular Medicine, Clinical Research Center, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Smith CIE; Biomolecular Medicine, Clinical Research Center, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Wood MJA; College of Agricultural Engineering Sciences, Salahaddin University-Erbil, Erbil, Iraq.
  • Vandenbroucke RE; Biomolecular Medicine, Clinical Research Center, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Nordin JZ; Cardiovascular Medicine Unit, Department of Medicine, Solna, Karolinska Institute, Stockholm, Sweden.
  • El-Andaloussi S; Evox Therapeutics Limited, Oxford, UK.
Nat Biomed Eng ; 5(9): 1084-1098, 2021 09.
Article en En | MEDLINE | ID: mdl-34616047
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vesículas Extracelulares / Enfermedades Neuroinflamatorias Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Nat Biomed Eng Año: 2021 Tipo del documento: Article País de afiliación: Suecia Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vesículas Extracelulares / Enfermedades Neuroinflamatorias Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Nat Biomed Eng Año: 2021 Tipo del documento: Article País de afiliación: Suecia Pais de publicación: Reino Unido