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Synthetic Antibodies Neutralize Covid-19 Virus Proteins

SARS-Cov-2 virus

Scanning electron microscope image of SARS-Cov-2 virus, responsible for Covid-19 infections (NIH.gov)

2 Sept. 2020. A company developing synthetic genetic materials and proteins says independent tests show its artificial antibodies neutralize infection mechanisms in Covid-19 viruses. Twist Bioscience Corp. in South San Francisco, California says tests of its synthetic antibodies were carried out and verified separately by labs at two different universities.

Twist Bioscience develops synthetic genetic materials on a silicon platform, patterned after semiconductors, instead of traditional plastic plates and receptacles. This process, says the company, overcomes conventional limitations and inefficiencies to design and construct genes, oligonucleotide collections for Crispr genome-editing RNA, and libraries of genetic variations. Twist says its process based on semiconductors makes it possible to reduce the chemical reaction volumes required, but at the same time increase production throughput by a factor of 1,000. As a result, says the company, it can produce 9,600 genes on a single chip, while traditional plastic lab plates produce a single gene in the same space.

The company says it first screened its library of 10 billion antibody sequences to identify 200 monoclonal, or highly targeted synthetic antibody candidates. These candidates were assessed for their ability to bind to the characteristic S1 spike glycoprotein on the surface of SARS-CoV-2 viruses, which in turn binds to receptors in human cells to begin the infection process. The antibodies were also evaluated by their ability to protect the angiotensin coverting enzyme 2, or ACE2, receptors, the targets of the S1 spike proteins that trigger Covid-19 infections.

The antibodies emerging from this screening process were either synthetic human immunoglobulin G, or IgG, antibodies or VHH nanobodies, for very heavy human single-domain proteins with characteristics of antibodies. Despite their name, VHH nanobodies have a smaller size and lighter weight that enables them to hit smaller targets more precisely than full-sized antibodies, and are also more thermally and chemically stable.

James Brien, an immunologist at St. Louis University medical school conducted the initial tests of the antibody candidates for Twist Bioscience. “All antibodies moving through clinical development for the treatment of Covid-19 are full IgG antibodies and already show promise in early studies,” says Brien in a Twist Bioscience statement. He adds that “nanobodies included in these neutralization assays may represent a different therapeutic path to treat the disease. Given their very small size in comparison to IgG antibodies, they may be able to access epitopes on the virus that are unavailable to full IgGs.” Epitopes are binding sites for antibodies.

Richard Bowen, professor of genetics and biotechnology at Colorado State University’s veterinary medicine school, verified Brien’s analysis. Bowen notes that results from both the IgG and nanobody analysis, “warrant advancement of several of these compounds into animal studies and potentially into human clinical trials.”

Emily Leproust, founder and CEO of Twist Bioscience says, “the neutralizing effects seen in these in vitro studies suggest that infections in humans could be blocked. We are now evaluating the best path forward for these neutralizing antibodies to support the fight against Covid-19.”

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