Scientists have published preliminary findings indicating that two variants of CRISPR Cas9 might not work for most humans.(Photo Credit: MIT News)

A paper published last week has highlighted that an element of the CRISPR-Cas9 gene-editing technique could trigger immune responses with potentially serious implications for the use of CRISPR therapies. The issue is down to the fact widely-used homologs of the Cas9 protein are derived from the bacteria Staphylococcus aureus and Streptococcus pyogenes.

In the paper, researchers conducted blood tests on a few dozen people and found that 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 authors continued:“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.”

The new study should not put a brake on developing CRISPR therapies, agreed Dr. Matthew Porteus of Stanford, a senior author of the paper and who is himself at work on a CRISPR-based therapy for sickle cell disease. But he said he and his colleagues investigated the immune issues because he felt they were being overlooked as the excitement around CRISPR grew.

“Like any new technology, you want to identify potential problems and engineer solutions for them,” Porteus said. “And I think that’s where we’re at. This is an issue that should be addressed.”

This type of gene-editing tech is still in the very early stages and with the pace of development across the field and to circumvent the issue will be explored on multiple fronts. As always with new therapies, the battle is both for efficacy as well as safety, but with possible cures at stake, you can bet no stone will be left unturned to get CRISPR safely into humans.