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Developing a treatment that better affects the SARS-CoV-2 variants

It takes a step closer to developing a treatment that better affect the SARS-CoV-2 variants by engineering exosome

Prof. Wonsik Lee, Dr. Hakgyun Kim

  • Developing a treatment that better affects the SARS-CoV-2 variants
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The Sungkyunkwan university-Korea Centres for Disease Control joint research team has developed an exosome-based treatment that protects against SARS-CoV-2 infection. Through this research jointly conducted by Professor Dong-Gyu Jo and Wonsik Lee of School of Pharmacy Sungkyunkwan University, they designed exosome-based approach to deliver therapeutic proteins, confirming its potential as a protein delivery system.

Since the winter of 2019, many people worldwide have been suffering from the coronavirus outbreak to this day. Although mRNA-based next-generation vaccines have been introduced, pandemics continue to occur as the effectiveness of vaccines gradually decreases due to variants that occur continuously.

One of the major treatments for COVID-19 is neutralizing antibody therapy. However, these antibody therapeutics have a disadvantage in that continuously emerging variants could reduce the efficacy against the virus. The exosome-based virus neutralization strategy developed to overcome these shortcomings was designed using the binding affinity between ACE2, a cellular receptor of SARS-CoV-2, and the virus envelope protein, SPIKE protein. This strategy was based on the fact that highly infectious virus mutants increase the affinity of the SPIKE protein for ACE2. In addition, using variants of the ACE2 protein known to increase affinity for the SPIKE protein, its efficacy was further enhanced.

The soluble ACE2 (sACE2) protein for virus neutralization and its variants were fused with an exosome-specific marker on the exosome surface to overcome the limited pharmacokinetics characteristics of using recombinant protein only. This method confirmed that pharmacokinetic and pharmacodynamic properties were improved while using a smaller amount of ACE2 protein than when recombinant protein was used, thereby showing excellent efficacy.

※ SPIKE protein: The envelope protein of SARS-CoV-2. It plays an essential role in host cell receptor recognition and fusion with the host cell membrane.

※ sACE2 (Soluble Angiotensin Converting Enzyme2) protein: A fragment protein that is formed by cleaving the extracellular part of this ACE2 protein.

Engineered exosomes inhibit the entry of wild-type and other variants of SARS-CoV-2 pseudovirus, and protect against authentic SARS-CoV-2 and Delta variant infection. The therapeutic efficacy of the engineered exosome against SARS-CoV-2 challenge was confirmed using K18-hACE2 mice.

Prof. Jo said, “We presented the new strategy engineering exosome for COVID-19 treatment agent in this study.” He said, “It will become a new driving force for the development of new therapeutics such as exosome-based COVID-19 and various diseases being developed through joint research with Exostemtech.”

The National Research Foundation of Korea supported this study. This work was also supported by a grant from the Ministry of Oceans and Fisheries’ R&D project, Korea, Korea Basic Science Institute (National Research Facilities and Equipment Center) grant funded by the Ministry of Education, Korea Disease Control and Prevention Agency, and the Korea National Institute of Health fund.

(Figure 1. Schematic illustration of SARS-CoV-2 infection and the application of engineered exosome for the neutralization of SARS-CoV-2.)

The research results were published in the Journal of Extracellular Vesicles (IF = 25.841) online on January 4, 2022.