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

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review

8 Scopus Citations
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Author(s)

  • Migara K. Jayasinghe
  • Chang Gao
  • Gracemary Yap
  • Brendon Zhi Jie Yeo
  • 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

Detail(s)

Original languageEnglish
Pages (from-to)21639-21661
Journal / PublicationACS Nano
Volume17
Issue number21
Online published18 Oct 2023
Publication statusPublished - 14 Nov 2023

Link(s)

Abstract

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. © 2023 The Authors. Published by American Chemical Society.

Research Area(s)

  • antisense oligonucleotides, apoptotic mimicry, extracellular vesicles, SARS-CoV-2, viral inhibition

Citation Format(s)

Red Blood Cell-Derived Extracellular Vesicles Display Endogenous Antiviral Effects and Enhance the Efficacy of Antiviral Oligonucleotide Therapy. / Jayasinghe, Migara K.; Gao, Chang; Yap, Gracemary et al.
In: ACS Nano, Vol. 17, No. 21, 14.11.2023, p. 21639-21661.

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review

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