Mechanism of SARS-CoV-2 inhibition mediated by extracellular vesicles (EVs). Credit:ACS Nano (2023). DOI: 10.1021/acsnano.3c06803
The COVID-19 pandemic has demonstrated the importance of preparing for drug interventions to contain viral outbreaks that could otherwise have devastating consequences. In preparing for the next pandemic, or Disease X, there is an urgent need for versatile platform technologies that could be repurposed at short notice to combat infectious outbreaks.
A team of researchers, led by Assistant Professor Minh Le from the Institute of Digital Medicine (WisDM) and the Department of Pharmacology at the National University of Singapore’s Yong Loo Lin School of Medicine (NUS Medicine), found that Nanoscale particles released by cells, called “extracellular vesicles” (EVs), can curb the viral infectivity of SARS-CoV-2 – its wild type and variants – and potentially other infectious diseases.
Asst Prof Le said: “Our study showed that these cell-derived nanoparticles are effective carriers of drugs that precisely target viral genes. These EVs are therefore an effective tool for therapeutic intervention in patients infected with COVID-19 or other infectious diseases. diseases.”
The study, conducted in collaboration with NUS Medicine’s Biosafety Level 3 (BSL3), the National University of Singapore’s Singapore Institute of Cancer Sciences and the School of Physical and Mathematical Sciences of the Nanyang Technological University (NTU), demonstrated potent inhibition of COVID-19 infection in laboratory models using a combination of EV-based inhibition and antisense oligonucleotide (ASO)-mediated antisense RNA therapy.
Inhibition of SARS-CoV-2 virus infection by red blood cell extracellular vesicles (RBCEV). Credit: Trinh Tran
A versatile tool that can be applied to any gene of interest, ASOs can recognize and bind to complementary regions of target RNA molecules and induce their inhibition and degradation.
In the study, published in ACS NanoThe authors used EVs derived from human red blood cells to deliver ASOs to key sites infected with SARS-CoV-2, thereby resulting in effective suppression of SARS-CoV-2 infection and replication.
The researchers also found that EVs exhibited distinct antiviral properties, capable of inhibiting viral infection pathways mediated by phosphatidylserine (PS) receptors, a key pathway used by many viruses to facilitate viral infection. . These viral inhibitory mechanisms were applicable to multiple SARS-CoV-2 variants, including delta and omicron strains, ensuring their broad effectiveness against SARS-CoV-2 infection.
The study results indicate that antisense RNA therapy with ASOs is a potentially effective approach that could be used to combat future viral outbreaks. The platform that was developed to deliver ASOs via EV to target SARS-CoV-2 viral genes can be easily applied to treat other viral infections by replacing the ASO sequences with those complementary to the target viral genes.
Asst Prof Le and his graduate students Migara Jay and Gao Chang, the first authors of the study, are currently developing more potent combinations of ASOs using artificial intelligence prediction models to achieve enhanced viral inhibition. This collaborative effort includes a partnership with the research teams of Associate Professor Edward Chow from WisDM, NUS Medicine and the BSL3 Center at NUS Medicine.
Associate Professor Justin Chu, Director of the BSL3 Center at NUS Medicine and co-author of the study, added: “This remarkable extracellular vesicle-based delivery platform technology coupled with antiviral therapy holds great promise in combating a wide range of viruses. and even disease X.”
The latter is a general description of emerging and unknown infectious threats, such as novel coronaviruses. The term has been used to alert and encourage the development of technological platforms, including vaccines, drug therapies and diagnostic tests, which could be rapidly customized and then deployed against future epidemics and pandemics. Assoc Prof Chu is also part of NUS Medicine’s Infectious Disease Translational Research Program.
Professor Dean Ho, Chair Professor and Director of WisDM at NUS Medicine, said: “This work brings the scalable and well-tolerated extracellular vesicle-based drug delivery platform one step closer to an important step towards studies of clinical validation. »
More information:
Migara K. Jayasinghe et al, Red blood cell-derived extracellular vesicles display endogenous antiviral effects and enhance the efficacy of antiviral oligonucleotide therapy, ACS Nano (2023). DOI: 10.1021/acsnano.3c06803
Provided by the National University of Singapore
Quote: Nanometer-sized cellular particles are a promising intervention tool in the treatment of infectious diseases, according to a study (November 28, 2023) retrieved November 28, 2023 from
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