2019-12-05| Technology

Broad Institute and Cyrus Biotech Join Hands to Develop Safe CRISPR

by Rajaneesh K. Gopinath
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By Rajaneesh K. Gopinath, Ph.D.

Broad Institute researchers under the leadership of CRISPR pioneer Feng Zhang is entering a scientific collaboration with the Seattle-based biotech software company, for developing a safer gene-editing technology for use in therapies.

The discovery of CRISPR/Cas9 gene editing is one of the biggest breakthroughs of our time. Initially identified in bacteria and archaea as an intricately evolved adaptive immune system, it was quickly adopted for gene-editing in various organisms including humans. It is a powerful tool since all it takes is a guide RNA and a Cas9 protein to trigger an almost precise modification of DNA. However, there have been reports of non-specific, off-target mutations that researches are trying to fix with newer advancements.


Cas9 Immunity

Several preliminary attempts at using CRISPR for the treatment of diseases are ongoing. Last April, a phase I clinical trial in cancer immunotherapy was carried out at the University of Pennsylvania making it the first time CRISPR was used in humans in the US. Apart from off-target effects, another well-documented obstacle in using gene editing is the preexisting humoral and cell-mediated adaptive immune responses to Cas9 in humans. Using ELISA, the authors of a study published in Nature Medicine detected antibodies against Cas9 from Staphylococcus aureus and Streptococcus pyogenes in 78% and 58% of donors, respectively. This is not surprising since these pathogens cause common diseases in humans. However, scientists say that it is not an unsolvable problem. Earlier in April, a team of researchers from Arizona State University engineered a Cas9 that lacked the epitopes to trigger the immune system. The modified Cas9 showed a 25-30-fold reduction in T-cell reactivity.


Broad-Cyrus Biotech Collaboration

Now, researchers from Cyrus biotechnology and the Broad Institute are coming together to combat the issue of immune responses against CRISPR. They will use the world’s leading protein modeling and design software platform of Cyrus called Rosetta. The software is a product of Prof. David Baker’s laboratory at the University of Washington. Feng Zhang will be the principal investigator of this collaboration. The resulting data will be made freely available to the scientific community for further research through publications in peer-reviewed journals.

Issi Rozen, chief business officer at the Broad Institute, said, “Broad researchers and their collaborators have pioneered the development and sharing of new genome editing tools, such as CRISPR-Cas9, which are revolutionizing and accelerating nearly every aspect of disease research and drug discovery around the world. With this collaboration, scientists will continue to improve the technology towards new tools and therapeutics, important to benefiting patients in the long term.”

Cyrus CEO Dr. Lucas Nivón added, “We have validated our computational deimmunization platform in a variety of systems, and now seek to apply it where it can make a major impact. Given the extensive therapeutic possibilities of CRISPR systems, and the leading position the Broad Institute and Dr. Zhang hold, we are very excited to work in partnership with them to make these molecules more amenable for use in humans with maximal efficacy and minimal side effects.”




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