Red Blood Cell-Derived Extracellular Vesicles Display Endogenous Antiviral Effects and Enhance the Efficacy of Antiviral Oligonucleotide Therapy

作者：Jayasinghe, Migara K.; Gao, Chang; Yap, Gracemary; Yeo, Brendon Zhi Jie; Vu, Luyen Tien; Tay, Douglas Jie Wen; Loh, Wen Xiu; Aw, Zhen Qin; Chen, Huixin; Phung, Dai Cao; Hoang, Dong Van; Prajogo, Rebecca Carissa; Hooi, Lissa; Lim, Fang Qing; Pirisinu, Marco; Mok, Chee Keng; Lim, Kah Wai; Tang, Sze Jing; Tan, Kai Sen; Chow, Edward Kai-Hua; Chen, Leilei; Phan, Anh Tuan; Chu, Justin Jang Hann; Le, Minh T. N.

来源：ACS Nano, 2023, 17(21): 21639-21661.

DOI：10.1021/acsnano.3c06803

• extracellular vesicles
• SARS-CoV-2
• antisenseoligonucleotides
• viral inhibition
• apoptotic mimicry

The COVID-19 pandemic has resulted in a large number of fatalities and, at present, lacks a readily available curative treatment for patients. Here, we demonstrate that unmodified red blood cell-derived extracellular vesicles (RBCEVs) can inhibit SARS-CoV-2 infection in a phosphatidylserine (PS) dependent manner. Using T cell immunoglobulin mucin domain-1 (TIM-1) as an example, we demonstrate that PS receptors on cells can significantly increase the adsorption and infection of authentic and pseudotyped SARS-CoV-2 viruses. RBCEVs competitively inhibit this interaction and block TIM-1-mediated viral entry into cells. We further extend the therapeutic efficacy of this antiviral treatment by loading antisense oligonucleotides (ASOs) designed to target conserved regions of key SARS-CoV-2 genes into RBCEVs. We establish that ASO-loaded RBCEVs are efficiently taken up by cells in vitro and in vivo to suppress SARS-CoV-2 replication. Our findings indicate that this RBCEV-based SARS-CoV-2 therapeutic displays promise as a potential treatment capable of inhibiting SARS-CoV-2 entry and replication.

• 单位
  南阳理工学院