Novel Gene Therapy May Express COVID-19 Antibodies in Lungs of Patients for Rapid Protection

    By Kathleen Berger, Executive Director for Science & Technology

    St. Louis-based Precision Virologics has made significant progress on a COVID-19 nasal spray vaccine that’s investigated in a human clinical trial in India, but that’s not all the academic spinoff is working on.

    “We’re using gene therapy,” said David T. Curiel, MD, PhD, Interim CEO for Precision Virologics. “We’re taking the gene for the antibody to express anti-COVID antibodies in the lung.”

    As professor of radiation oncology for Washington University School of Medicine in St. Louis, Curiel’s research team has designed a novel gene therapy using a method of gene transfer to directly express COVID-19 antibodies in the lungs of patients. This would provide rapid protection for those who are infected with COVID-19.

    “This relates to people who have already contracted the disease,” Curiel explained. “So we’re not trying to immunize them, we’re trying to protect them”

    In January 2021, Curiel’s research received an added boost of more than $400,000 from the National Institutes of Health. His lab receives about $2 million a year from the NIH, with considerable funding dedicated to COVID-19 research in 2020. That covered the initial stages of this gene therapy research.

    “We’ve developed gene transfer vectors that deliver genes to the lung, genetically inducing the expression of the antibodies in the lung.”

    The novel vector platform for gene therapy uses a method of gene transfer involving Michael Diamond, MD, PhD, professor of molecular microbiology, and of pathology and immunology at Washington University School of Medicine.

    “Michael Diamond has developed genes for these antibodies so now we just have to put them together and test them in a model system,” said Curiel.

    Diamond is scientific advisor for Precision Virologics.

    “You basically take a piece of the virus, the spike gene which is the target of antibody responses,” explained Diamond. “And then stitch it into what was another virus, an adenovirus. You take the spike gene and you put it in a defective adenovirus. We use it as what we call a vector – a way to get the gene that we want, which in this case is the spike gene – into cells very efficiently because viruses know how to deliver genes. It has the DNA which then encodes the mRNA for the spike gene. And then you produce that protein, and that protein invokes the immune response. But that adenovirus never spreads again. And that induces immunity right there.”

    “The person’s lung makes the antibody right at the sight of action,” added Curiel.

    This is different from what’s offered by pharmaceutical companies like Regeneron and Eli Lily. Those are monoclonal antibody therapies that give pre-formed antibodies.

    “One strategy for people who already have COVID and are sick in the ICU is to give antibodies, like former President Trump received,” said Curiel. “But there are a lot of problems with that. You have to manufacture them, you have to scale them, you have to purify them.”

    That’s why Curiel hopes to offer gene transfer an alternative for delivering antibodies. The goal is for the therapy to protect people from COVID-19 if they have been exposed, or to treat them if they are suffering from infection.

    “Our strategy conceivably lets them develop antibodies within hours so we are excited that this can evolve into a rapid protection that compliments the ongoing vaccine efforts,” said Curiel.

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