Immunity May Make CRISPR-Based Therapies Ineffective

Researchers identify antibodies for two commonly used Cas9 proteins in human blood. Investors take notice.

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© BRYAN SATALINOCRISPR-Cas9 has been hailed as a breakthrough tool in genome editing that could usher in an era of precision gene therapy, and clinical trials are already scheduled to begin this year. But there may be a snag: our own immune systems.

The technique relies on Cas9 nucleases found in bacteria. But the majority of humans may have preexisting immune responses to bacteria from which the most common Cas9 homologs are derived, according to a preprint published last week (January 5) on bioRxiv.

The study, as MIT Technology Review first reported, examined the blood of 12 adults and 22 newborns for antibodies to Cas9 proteins from Staphylococcus aureus and Streptococcus pyogenes. They found antibodies for S. pyogenes in 65 percent of donors and antibodies for S. aureus in 75 percent—and nearly half of the donors had CD4+ T-cells that specifically targeted Cas9 homologs from S. aureus.

The immunity could not only limit the effectiveness of CRISPR, but also “create safety concerns,” the researchers write in the study. ...

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