DataVXACS NanoPaper
journal article·2023-11-14Open access

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

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

ACS Nano· Volume 17· Issue 21
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Abstract

High Resolution Image Download MS PowerPoint Slide 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.
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Research context

OpenAlex topics: Extracellular vesicles in disease · Viral Infections and Vectors · Mosquito-borne diseases and control

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Institute for Digital Medicine and Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 16 Medical Drive, Singapore 117600, Singapore

Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road, Singapore 119228, Singapore

Infectious Diseases Translational Research Programme and Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, 16 Medical Drive, Singapore 117545, Singapore

Biosafety Level 3 Core Facility, Yong Loo Lin School of Medicine, National University of Singapore, 14 Medical Drive, Singapore 117599, Singapore

Cancer Science Institute, Yong Loo Lin School of Medicine, National University of Singapore, 16 Medical Drive, Singapore 117599, Singapore

Department of Biomedical Sciences, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong SAR 999077, China

Division of Physics & Applied Physics, School of Physical & Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, Singapore 637371, Singapore

Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, 16 Medical Drive, Singapore 117594, Singapore

Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, 61 Biopolis Drive, Singapore 138673, Singapore

Funding

Agency for Science, Technology and Research · National Medical Research Council · Ministry of Education - Singapore · National Research Foundation Singapore · Ministry of Health -Singapore · National University of Singapore

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