Publication date: Jul 17, 2025
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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| Concepts | Keywords |
|---|---|
| Antiviral | Extracellular vesicles |
| Cd63 | Neural stem cell |
| Nanobodies | SARS-CoV-2 |
| Transcriptomics | Spike protein |
| Vivo | VHH72 |
Semantics
| Type | Source | Name |
|---|---|---|
| disease | MESH | infection |
| disease | MESH | inflammation |
| disease | IDO | cell |
| disease | IDO | protein |
| disease | MESH | COVID 19 |
| drug | DRUGBANK | Coenzyme M |
| drug | DRUGBANK | Trestolone |
| pathway | KEGG | Viral replication |
| disease | MESH | Hematological Malignancy |
| disease | IDO | facility |
| drug | DRUGBANK | Methylcellulose |
| drug | DRUGBANK | Formaldehyde |
| drug | DRUGBANK | Gentian violet cation |
| drug | DRUGBANK | Indoleacetic acid |
| disease | IDO | assay |
| drug | DRUGBANK | Aspartame |
| disease | IDO | production |
| pathway | REACTOME | Release |
| drug | DRUGBANK | Cysteamine |
| drug | DRUGBANK | Tretamine |
| drug | DRUGBANK | Water |
| drug | DRUGBANK | Copper |
| drug | DRUGBANK | Activated charcoal |
| drug | DRUGBANK | Medical air |
| drug | DRUGBANK | Iodide |
| drug | DRUGBANK | Isoflurane |
| disease | IDO | nucleic acid |
| disease | IDO | algorithm |
| disease | IDO | host |
| disease | MESH | viral load |
| disease | MESH | viremia |