About: Engineering of extracellular vesicles for display of protein biotherapeutics

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An Entity of Type : schema:ScholarlyArticle, within Data Space : wasabi.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
title	Engineering of extracellular vesicles for display of protein biotherapeutics
Creator	Seow, Yiqi Xin, Yi Wood, Matthew Roberts, Thomas Smith, C Vandenbroucke, Roosmarijn Lee, Fiona Balsu, Sriram Bostancioglu, Beklem Bäcklund, Alexandra Conceição, Mariana Corso, Giulia El, Samir Felldin, Ulrika Gupta, Dhanu Gustafsson, Manuela Görgens, André Hean, Justin Liang, Xiuming Mohammad, Dara Mäger, Imre Nordin, Joel Sork, Helena Wiklander, Oscar
source	BioRxiv
abstract	Extracellular vesicles (EVs) have recently emerged as a highly promising cell-free bio-therapeutics. While a range of engineering strategies have been developed to functionalize the EV surface, current approaches fail to address the limitations associated with endogenous surface display, pertaining to the heterogeneous display of commonly used EV-loading moieties among different EV subpopulations. Here we present a novel engineering platform to display multiple protein therapeutics simultaneously on the EV surface. As proof-of-concept, we screened multiple endogenous display strategies for decorating the EV surface with cytokine binding domains derived from tumor necrosis factor receptor 1 (TNFR1) and interleukin 6 signal transducer (IL6ST), which can act as decoys for the pro-inflammatory cytokines TNFα and IL6, respectively. Combining synthetic biology and systematic screening of loading moieties, resulted in a three-component system which increased the display and decoy activity of TNFR1 and IL6ST, respectively. Further, this system allowed for combinatorial functionalization of two different receptors on the same EV surface. These cytokine decoy EVs significantly ameliorated disease phenotypes in three different inflammatory mouse models for systemic inflammation, neuroinflammation, and intestinal inflammation. Importantly, significantly improved in vitro and in vivo efficacy of these engineered EVs was observed when compared directly to clinically approved biologics targeting the IL6 and TNFα pathways.
has issue date	2020-06-15(xsd:dateTime)
bibo:doi	10.1101/2020.06.14.149823
has license	biorxiv
sha1sum (hex)	792474c9d2290d9964a167f2ad0823ca4b5def93
schema:url	https://doi.org/10.1101/2020.06.14.149823
resource representing a document's title	Engineering of extracellular vesicles for display of protein biotherapeutics
schema:publication	bioRxiv
resource representing a document's body	covid:792474c9d2290d9964a167f2ad0823ca4b5def93#body_text
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