Intranasal delivery of engineered anti-SARS-CoV-2 extracellular vesicles therapeutically represses lung infection and inflammation
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Shrivastava, Surya
Gao, Wenqing
Supramaniam, Aroon
Tayyar, Yaman
West, Nicholas P
Kelly, Gabrielle
Acharya, Dhruba
McMillan, Nigel AJ
Morris, Kevin V
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Abstract
Extracellular vesicles (EVs) are amenable to genetic engineering in that EVs can be endowed with surface armaments that can directly bind to target molecules or receptors. We previously developed HEK293 cell-derived EVs that contain a novel fusion tetraspanin protein, CD63, embedded within a highly conserved anti-SARS-CoV-2 nanobody, VHH72. These anti-SARS-CoV-2-enriched EVs bind SARS-CoV-2 spike protein and can functionally neutralize SARS-CoV-2 in vitro. Here, we extend our observations in vivo using EVs derived from neural stem cells (NSCs) and demonstrated the antiviral effectiveness of these direct-acting EVs in the lungs of SARS-CoV-2 infected mice when administered intranasally post-infection. Using NanoString-based immune transcriptomics we showed that these EVs exert mild anti-inflammatory effects on SARS-CoV-2 infected lungs. This is the first demonstration of the effective use of intranasally delivered EVs ladened with anti-SARS-CoV-2 nanobodies in vivo.
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Drug Delivery and Translational Research
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© The Author(s) 2025. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
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Respiratory diseases
Pharmacology and pharmaceutical sciences
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Idris, A; Shrivastava, S; Gao, W; Supramaniam, A; Tayyar, Y; West, NP; Kelly, G; Acharya, D; McMillan, NAJ; Morris, KV, Intranasal delivery of engineered anti-SARS-CoV-2 extracellular vesicles therapeutically represses lung infection and inflammation, Drug Delivery and Translational Research, 2025