Armstrong, J. P. K., Holme, M. N. & Stevens, M. M. Re-engineering extracellular vesicles as smart nanoscale therapeutics. ACS Nano 11, 69–83 (2017).
Google Scholar
Alvarez-Erviti, L. et al. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat. Biotechnol. 29, 341–345 (2011).
Google Scholar
El-Andaloussi, S. et al. Exosome-mediated delivery of siRNA in vitro and in vivo. Nat. Protoc. 7, 2112–2126 (2012).
Google Scholar
Wiklander, O. P. B. et al. Extracellular vesicle in vivo biodistribution is determined by cell source, route of administration and targeting. J. Extracell. Vesicles https://doi.org/10.3402/jev.v4.26316 (2015).
Cooper, J. M. et al. Systemic exosomal siRNA delivery reduced alpha-synuclein aggregates in brains of transgenic mice. Mov. Disord. 29, 1476–1485 (2014).
Google Scholar
Jeppesen, D. K. et al. Reassessment of exosome composition. Cell 177, 428–445 (2019).
Google Scholar
Willms, E. et al. Cells release subpopulations of exosomes with distinct molecular and biological properties. Sci. Rep. 6, 22519 (2016).
Google Scholar
Vagner, T. et al. Protein composition reflects extracellular vesicle heterogeneity. Proteomics 19, 1800167 (2019).
Google Scholar
Crescitelli, R. et al. Subpopulations of extracellular vesicles from human metastatic melanoma tissue identified by quantitative proteomics after optimized isolation. J. Extracell. Vesicles 9, 1722433 (2020).
Google Scholar
Kim, E. Y. & Moudgil, K. D. Immunomodulation of autoimmune arthritis by pro-inflammatory cytokines. Cytokine 98, 87–96 (2017).
Google Scholar
Moudgil, K. D. & Choubey, D. Cytokines in autoimmunity: role in induction, regulation, and treatment. J. Interferon Cytokine Res. 31, 695–703 (2011).
Google Scholar
Garbers, C., Heink, S., Korn, T. & Rose-John, S. Interleukin-6: designing specific therapeutics for a complex cytokine. Nat. Rev. Drug Discov. 17, 395–412 (2018).
Google Scholar
Kalliolias, G. D. & Ivashkiv, L. B. TNF biology, pathogenic mechanisms and emerging therapeutic strategies. Nat. Rev. Rheumatol. 12, 49–62 (2016).
Google Scholar
Sedger, L. M. & McDermott, M. F. TNF and TNF-receptors: from mediators of cell death and inflammation to therapeutic giants – past, present and future. Cytokine Growth Factor Rev. 25, 453–472 (2014).
Google Scholar
Wolf, J., Rose-John, S. & Garbers, C. Interleukin-6 and its receptors: a highly regulated and dynamic system. Cytokine 70, 11–20 (2014).
Google Scholar
Simpson, R. J., Kalra, H. & Mathivanan, S. Exocarta as a resource for exosomal research. J. Extracell. Vesicles 1, 18374 (2012).
Google Scholar
Hurwitz, S. N. et al. Proteomic profiling of NCI-60 extracellular vesicles uncovers common protein cargo and cancer type-specific biomarkers. Oncotarget 7, 86999–87015 (2016).
Google Scholar
Sork, H. et al. Heterogeneity and interplay of the extracellular vesicle small RNA transcriptome and proteome. Sci. Rep. 8, 10813 (2018).
Google Scholar
Xanthoulea, S. et al. Tumor necrosis factor (TNF) receptor shedding controls thresholds of innate immune activation that balance opposing TNF functions in infectious and inflammatory diseases. J. Exp. Med. 200, 367–376 (2004).
Google Scholar
Meier, S., Güthe, S., Kiefhaber, T. & Grzesiek, S. Foldon, the natural trimerization domain of T4 fibritin, dissociates into a monomeric A-state form containing a stable β-hairpin: atomic details of trimer dissociation and local β-hairpin stability from residual dipolar couplings. J. Mol. Biol. 344, 1051–1069 (2004).
Google Scholar
Ellenberger, T. E., Brandl, C. J., Struhl, K. & Harrison, S. C. The GCN4 basic region leucine zipper binds DNA as a dimer of uninterrupted α helices: crystal structure of the protein-DNA complex. Cell 71, 1223–1237 (1992).
Google Scholar
Jensen, M. R. et al. Structural description of the nipah virus phosphoprotein and its interaction with stat1. Biophys. J. https://doi.org/10.1016/j.bpj.2020.04.010 (2020).
Sliepen, K., van Montfort, T., Melchers, M., Isik, G. & Sanders, R. W. Immunosilencing a highly immunogenic protein trimerization domain. J. Biol. Chem. 290, 7436–7442 (2015).
Google Scholar
Dooley, K. et al. A versatile platform for generating engineered extracellular vesicles with defined therapeutic properties. Mol. Ther. 29, 1729–1743 (2021).
Google Scholar
Théry, C. et al. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. J. Extracell. Vesicles 7, 1535750 (2018).
Google Scholar
Wiklander, O. P. B. et al. Systematic methodological evaluation of a multiplex bead-based flow cytometry assay for detection of extracellular vesicle surface signatures. Front. Immunol. 9, 1326 (2018).
Google Scholar
Pelosi, L. et al. Increased levels of interleukin-6 exacerbate the dystrophic phenotype in mdx mice. Hum. Mol. Genet. 24, 6041–6053 (2015).
Google Scholar
Saleh, A. F. et al. Extracellular vesicles induce minimal hepatotoxicity and immunogenicity. Nanoscale 11, 6990–7001 (2019).
Google Scholar
Zhu, X. et al. Comprehensive toxicity and immunogenicity studies reveal minimal effects in mice following sustained dosing of extracellular vesicles derived from HEK293T cells. J. Extracell. Vesicles 6, 1324730 (2017).
Google Scholar
Sejwal, K. et al. Proteoliposomes—a system to study membrane proteins under buffer gradients by cryo-EM. Nanotechnol. Rev. 6, 57–74 (2017).
Google Scholar
Gupta, D. et al. Quantification of extracellular vesicles in vitro and in vivo using sensitive bioluminescence imaging. J. Extracell. Vesicles 9, 1800222 (2020).
Google Scholar
Desmet, J. et al. Structural basis of IL-23 antagonism by an Alphabody protein scaffold. Nat. Commun. 5, 5237 (2014).
Google Scholar
Göbel, K., Ruck, T. & Meuth, S. G. Cytokine signaling in multiple sclerosis: lost in translation. Mult. Scler. 24, 432–439 (2018).
Google Scholar
Görgens, A. et al. Optimisation of imaging flow cytometry for the analysis of single extracellular vesicles by using fluorescence-tagged vesicles as biological reference material. J. Extracell. Vesicles 8, 1587567 (2019).
Google Scholar
Reshke, R. et al. Reduction of the therapeutic dose of silencing RNA by packaging it in extracellular vesicles via a pre-microRNA backbone. Nat. Biomed. Eng. https://doi.org/10.1038/s41551-019-0502-4 (2020).
Kamerkar, S. et al. Exosomes facilitate therapeutic targeting of oncogenic KRAS in pancreatic cancer. Nature 546, 498–503 (2017).
Google Scholar
Corso, G. et al. Systematic characterization of extracellular vesicle sorting domains and quantification at the single molecule—single vesicle level by fluorescence correlation spectroscopy and single particle imaging. J. Extracell. Vesicles 8, 1663043 (2019).
Google Scholar
Gao, X. et al. Anchor peptide captures, targets, and loads exosomes of diverse origins for diagnostics and therapy. Sci. Transl. Med. 10, eaat0195 (2018).
Google Scholar
Wiklander, O. P. B., Brennan, M., Lötvall, J., Breakefield, X. O. & Andaloussi, S. E. L. Advances in therapeutic applications of extracellular vesicles. Sci. Transl. Med. 11, 8521 (2019).
Google Scholar
Rayamajhi, S. & Aryal, S. Surface functionalization strategies of extracellular vesicles. J. Mater. Chem. B 8, 4552–4569 (2020).
Google Scholar
Baietti, M. F. et al. Syndecan-syntenin-ALIX regulates the biogenesis of exosomes. Nat. Cell Biol. 14, 677–685 (2012).
Google Scholar
Fang, Y. et al. Higher-order oligomerization targets plasma membrane proteins and HIV Gag to exosomes. PLoS Biol. 5, e158 (2007).
Google Scholar
Conceição, M. et al. Engineered extracellular vesicle decoy receptor-mediated modulation of the IL6 trans-signalling pathway in muscle. Biomaterials 266, 120435 (2021).
Google Scholar
Lai, C. P. et al. Dynamic biodistribution of extracellular vesicles in vivo using a multimodal imaging reporter. ACS Nano 8, 483–494 (2014).
Google Scholar
Perets, N. et al. Golden exosomes selectively target brain pathologies in neurodegenerative and neurodevelopmental disorders. Nano Lett. 19, 3422–3431 (2019).
Google Scholar
Keller, M. D. et al. Decoy exosomes provide protection against bacterial toxins. Nature 579, 260–264 (2020).
Google Scholar
de Carvalho, J. V. et al. Nef neutralizes the ability of exosomes from CD4+ T cells to act as decoys during HIV-1 infection. PLoS ONE 9, e113691 (2014).
Google Scholar
Corso, G. et al. Reproducible and scalable purification of extracellular vesicles using combined bind-elute and size exclusion chromatography. Sci. Rep. 7, 11561 (2017).
Google Scholar
Tertel, T. et al. High-resolution imaging flow cytometry reveals impact of incubation temperature on labelling of extracellular vesicles with antibodies. Cytometry A 97, 602–609 (2020).
Google Scholar
Brkic, M. et al. Amyloid β oligomers disrupt blood–CSF barrier integrity by activating matrix metalloproteinases. J. Neurosci. 35, 12766–12778 (2015).
Google Scholar
Raduolovic, K., Mak’Anyengo, R., Kaya, B., Steinert, A. & Niess, J. H. Injections of lipopolysaccharide into mice to mimic entrance of microbial-derived products after intestinal barrier breach. J. Vis. Exp. https://doi.org/10.3791/57610 (2018).
Scheiffele, F. & Fuss, I. J. Induction of TNBS colitis in mice. Curr. Protoc. Immunol. https://doi.org/10.1002/0471142735.im1519s49 (2002).

