Idris Adi, Shrivastava Surya, Gao Wenqing, Supramaniam Aroon, Tayyar Yaman, West Nicholas P, Kelly Gabrielle, Acharya Dhruba, McMillan Nigel A J, Morris Kevin V
Institute of Biomedicine and Glycomics and School and Pharmacy and Medical Sciences, Griffith University, Southport, QLD, Australia.
Centre for Immunology and Infection Control, School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD, Australia.
Drug Deliv Transl Res. 2025 Jul 17. doi: 10.1007/s13346-025-01922-9.
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.
细胞外囊泡（EVs）适合进行基因工程改造，因为可以赋予EVs能够直接结合靶分子或受体的表面装备。我们之前开发了源自人胚肾293细胞（HEK293）的EVs，其包含一种新型融合四跨膜蛋白CD63，该蛋白嵌入高度保守的抗SARS-CoV-2纳米抗体VHH72中。这些富含抗SARS-CoV-2的EVs可结合SARS-CoV-2刺突蛋白，并能在体外功能性中和SARS-CoV-2。在此，我们利用源自神经干细胞（NSCs）的EVs在体内扩展了我们的观察结果，并证明了这些直接作用的EVs在感染后经鼻给药时对SARS-CoV-2感染小鼠肺部具有抗病毒效力。使用基于NanoString的免疫转录组学技术，我们表明这些EVs对SARS-CoV-2感染的肺部具有轻微的抗炎作用。这是首次证明在体内有效使用经鼻递送的负载抗SARS-CoV-2纳米抗体的EVs。
