A new journal paper published late last week revealed that a “cutting” element of the CRISPR-Cas9 gene-editing technique could be under threat from the body’s own immune system.

The paper, published on bioRxiv (but as yet to be peer-reviewed), saw researchers undertake blood tests on a few dozen people. “The presence of pre-existing adaptive immune responses in humans to either Cas9 homolog may hinder the safe and efficacious use of the Cas9/gRNA system to treat disease, and may even result in significant toxicity to patients,” the study found.

This is because the most widely used homologs of the Cas9 protein are derived from the bacteria Staphylococcus aureus (S. aureus) and Streptococcus pyogenes (S. pyogenes).

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“Based on the fact that these two bacterial species cause infections in the human population at high frequencies, we looked for the presence of pre-existing adaptive immune responses to their respective Cas9 homologs, SaCas9 (S. aureus homolog of Cas9) and SpCas9 (S. pyogenes homolog of Cas9),” the researchers out of the Department of Pediatrics, Stanford University, say in the paper.

“To determine the presence of anti-Cas9 antibodies, we probed for the two homologs using human serum and were able to detect antibodies against both, with 79% of donors staining against SaCas9 and 65% of donors staining against SpCas9.”

In essence, humans are infected by these bacteria all the time, and thus many of us will have an immune response to deal with them. So, when using the Cas9 protein, which is where the so-called “snipping” tool of CRISPR-Cas9 comes from, many patients may not benefit as their immune systems will fight back.

This type of gene-editing tech is still in its infancy, and other techniques and systems can and likely will likely be tested to get around this potential problem; but in the short term, CRISPR biotechs, including Editas, Intellia and CRISPR Therapeutics, could see their stock take a hit.

The paper was published on Friday, Jan. 5; Editas was down afterhours Friday (and will be presenting at J.P. Morgan later this week), with Intellia and CRISPR following suit.

The authors conclude: “This [sic] data raises a potential barrier to the safe and efficacious use of the Cas9/gRNA system to treat disease […] In conclusion, our findings raise important new considerations in applying the Cas9/gRNA system to edit human cells for therapeutic purposes. In future work, more sensitive assays can be used to fully understand the pre-existing immune response in humans to Cas9 proteins.

“We believe our findings will stimulate crucial discussions in the genome editing community about how to most safely and effectively apply the Cas9/gRNA genome editing system for gene therapy in humans.”