139 — Identification of Pre-Existing Adaptive Immunity to Cas9 Proteins in Humans

The CRISPR-Cas9 system is hot these days.

CRISPR gene editing is currently the most promising, most precise method for modifying highly specific DNA sequences in vivo. However, most of the protocols designed around this gene combination have been only performed in non-human models, using Staph and Strep Cas9 protein homologs (dubbed SaCas9 and SpCas9, respectively). As a result, human immune response to these homologs hasn’t been well-researched.

These researchers call this omission into question: After all, Staph and Strep are two extremely common infections amongst humans. When they tested human serum, they discovered anitbodies against both of these homologs. In other words, human bodies might not only target and destroy gene therapies that use these Cas9 homologs…they might even reject them as toxic antigens, causing a serious immune response. (In existing therapies that use bacterial or viral vectors, patients’ immune systems often destroy or flush the treatment before it has a chance to work.)

This raises serious concerns as to whether CRISPR/Cas9 therapies that use these homologs are safe for human exposure. If patients do have an immune response to the therapy, the best case scenario is that the treatment fails. The worst case scenario is that they develop an immune response to otherwise safe compounds: there is precedent in the field of gene therapies for fatal immune response.