Cyrus Biotechnology and the Broad Institute of MIT and Harvard have teamed up to make gene editing with the CRISPR-Cas9 technology safer.
The multi-target collaboration, specific details of which are not being disclosed, aims to address longstanding concerns surrounding gene editing: some patients might be predisposed to an immune reaction to the DNA-cutting enzyme Cas9. That response could make the technology ineffective, or worse, harm the patient.
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Recent research has validated these concerns, revealing evidence of immunity against Cas9 enzymes in humans. Taking aim at what CEO Lucas Nivón says is the most problematic form, Cyrus can reduce or eliminate T-cell mediated (active) immunogenicity.
Based on the Rosetta software suite, the company’s so-called “computational deimmunization platform” uses structural biophysics and machine learning-based methods to help design CRISPR-Cas9 enzymes that are less likely to incite an immune response. The idea is to redesign only the problematic portions of the enzyme while retaining its overall function, Nivón tells Xconomy.
The method has been proven in three published proof of concept studies—one in mice and two in humans—and is being used in other undisclosed projects.
While there are multiple types of immunogenicity, others would likely have a more minor response, not limiting clinical use, Nivón explains, “whereas a strong allergic response or complete destruction of the CRISPR therapeutic would be a major problem.”
“As CRISPR gets into humans … we’re going to start to see how much of a problem each of those types of immunity is, and which one is most active,” he adds.
Gene-edited therapies have already made their way into human trials: Victoria Gray earlier this year became the first person in the US to receive a CRISPR-based medicine—an experimental treatment for sickle cell disease developed by CRISPR Therapeutics (NASDAQ: CRSP) and Vertex Pharmaceuticals (NASDAQ: VRTX). In very early results released last month, the companies reported no safety problems and some signs that the experimental therapy is working.
Additionally, Editas Medicine (NASDAQ: EDIT) in December 2018 received the green light from the FDA to proceed with clinical trial testing the first therapy that edits genes in vivo. The study, conducted in partnership with Allergan (NYSE: AGN), enrolled its first patient in September of this year and is estimated to be completed in 2024.
Results from the Cyrus and Broad collaboration will be published in peer-reviewed journals and any improved CRISPR model will be freely available to non-profits and academic scientists. Commercial use will be handled by the Broad, says Nivón. Feng Zhang will be the lead investigator on behalf of the Broad.
Spun out from David Baker’s laboratory at the University of Washington and the Howard Hughes Medical Institute (HHMI), Seattle, WA-based Cyrus is backed by investors including Trinity Ventures, Orbimed, Springrock Ventures, Alexandria Venture Investments, and W Fund.
(Image: iStock/Meletios Verras)