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Broad Inst, Biotech Partner on Immune-Safe Crispr

Feng Zhang

Feng Zhang (McGovern Institute, MIT)

3 Dec. 2019. A company designing synthetic proteins and the Broad Institute are developing ways to reduce the threat of edited genes producing an immune-system response. Financial and intellectual property details of the agreement between Cyrus Biotechnology Inc. in Seattle and the Broad Institute, a genomics research center affiliated with Harvard University and MIT, were not disclosed.

Cyrus Biotechnology and Broad Institute aim to enhance the genome editing technology Crispr to make it less likely for gene therapies using the technology to invoke an adverse reaction from the immune system. Crispr — clustered, regularly interspaced short palindromic repeats — is a genome editing technique derived from bacterial defense systems, using ribonucleic acid or RNA to identify and monitor precise locations in DNA for editing.

Broad Institute is a pioneer in the development of Crispr, with many of the institute’s recent advances in gene editing emerging from the lab of molecular biologist Feng Zhang, who leads the collaboration with Cyrus Biotechnology. In July, as reported in Science & Enterprise, Zhang and colleagues at Broad Institute and MIT introduced enhancements in Crispr to enable more edits in RNA. Later, another Broad Institute team published a more precise and efficient version of Crispr called prime editing that the authors say can correct up to 89 percent of known disease-causing genetic variations.

Cyrus Biotechnology offers protein modeling and design using computational techniques with a software package called Rosetta. The software was originally developed at University of Washington in the lab of biochemistry professor David Baker, part of the university’s Institute for Protein Design. Baker is a co-founder and scientific adviser to Cyrus that creates applications with Rosetta for the design of large, complex proteins from scratch to meet specific performance characteristics, without starting from a known protein model.

A design objective the company calls deimmunization is one of those performance characteristics. With deimmunization, Cyrus says its application can identify epitopes, or binding sites for antibodies, and remove them from the protein structure. With epitopes removed, says the company, the chance of provoking an immune response is reduced, making new therapeutic proteins safer for patients.

“We have validated our computational deimmunization platform in a variety of systems,” says Lucas Nivón, CEO of Cyrus Biotechnology in a company statement, “and now seek to apply it where it can make a major impact.”

Broad Institute and Cyrus Biotechnology expect to make the results of the collaboration widely available to encourage further development into therapies. The partners say they will publish their findings in peer-reviewed journals and make their work freely available to scientists at academic and not-for-profit institutions.

In January, Science & Enterprise reported on a similar application of Rosetta from Baker’s lab that produces cancer-fighting proteins invoking the immune system, but binding only to targeted sites on cancer cells. The proteins are designed as well to ignore binding at sites that may cause adverse reactions in patients. Another company, Neoleukin Therapeutics in Seattle, also co-founded by Baker, is commercializing this Rosetta application.

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