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Exosomes Shown to Block Broad Covid-19 Variant Range

Exosome illustration

Exosome illustration (NIH)

20 Jan. 2021. Tiny natural bubbles with infection-receptor proteins found in blood are shown in lab mice to divert and prevent SARS-CoV-2 viruses from infecting real cells. Researchers from M.D. Anderson Cancer Center in Houston and Northwestern University in Chicago report their findings in today’s issue of the journal Nature Communications, with the senior authors starting companies to commercialize the technology.

A team from labs headed by Raghu Kalluri at M.D. Anderson, and Huiping Liu and Deyu Fang at Northwestern, investigated therapeutic properties of exosomes, nanoscale natural oil extracellular vesicles or bubbles expressing angiotensin-converting enzyme 2 or ACE2 receptor proteins against SARS-CoV-2 viruses responsible for Covid-19. When SARS-CoV-2 viruses infect cells, their binding target is ACE2 receptor proteins. People with Covid-19 infections often produce exosomes with ACE2 proteins, carried in their blood plasma as part of the body’s anti-viral response, with the more severe the disease in an individual, the more ACE2-expressing exosomes produced.

In this case, the researchers are seeking to assess exosomes with ACE2 proteins on their surface as a treatment for Covid-19 infections. In people with Covid-19 infections, ACE2-expressing exosomes attract invading SARS-CoV-2 viruses away from their usual cellular targets, diminishing their impact. And since all known SARS-CoV-2 variants target these same ACE2 receptor proteins, the team hypothesized these exosomes they call evACE2 could reduce or block further infections from a wide range of these variants, if given as a therapy.

Up to now, Covid-19 therapies and vaccines target infecting proteins on the SARS-CoV-2 viral spike, with the chemistry of that spike protein changing with each mutation or variant in the virus. Treatments using evACE2, say the authors, would be designed to block all variations of the current or even future viruses, as long as they use the same infecting mechanism. Liu, in an M.D. Anderson statement notes that “the beauty of evACE2 is its superpower in blocking broad strains of coronaviruses, including current SARS-CoV-2 and even future SARS coronaviruses from infecting humans.”

Formulated into a nasal spray

The researchers conducted a series of lab and animal tests first to verify elevated levels of ACE2-expressing exosomes in Covid-19 patients, then to test for their therapeutic effects. Initial lab tests show blood samples from Covid-19 patients have higher levels evACE2 exosomes, which can also block infections from a broad range of SARS-CoV-2 variants. In the next stage, the team extracted evACE2 exosomes from plasma and refined the exosomes into nanoscale pellets, which in blood samples from Covid-19 patients, diverted and neutralized SARS-CoV-2 viruses.

The researchers then tested evACE2 exosomes formulated as a nasal spray given to mice genetically-altered to express human Covid-19 infections. The team sprayed the mice two to five days following their infections, which began showing signs of improvement by day six or seven, and full recovery within two weeks. In addition, 80 percent of infected mice given the evACE2 nasal spray were protected from Covid-19 lung injuries, with fewer infections and lower viral loads found in their lung cells.

“The key takeaway from this study,” says Kalluri, “is the identification of naturally occurring extracellular vesicles in the body that express the ACE2 receptor on their surface and serve as part of the normal adaptive defense against Covid-19-causing viruses.” He adds, “Building upon this, we’ve discovered a way to harness this natural defense as a new potential therapy against this devastating virus.”

Northwestern University holds or applied for patents on the evACE2 technology. Liu, Fang, and co-author Andrew Hoffman recently started the company ExoMira Medicine Inc. to develop and commercialize evACE2. And as reported in Science & Enterprise in Nov. 2015, Kalluri’s earlier research on exosomes is licensed to a company he co-founded, Codiak Biosciences in Cambridge, Mass.

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