CRISPR-Cas9’s compelling success in the lab made it seem like the genome-editing tool could well and truly be close to, if not exactly, a panacea.
CRISPR-Cas9’s compelling success in the lab made it seem like the genome-editing tool could well and truly be close to, if not exactly, a panacea. Scientists succeeded in editing the genome in human embryos last year, and in November, a US-based company even kicked off an experiment in which a patient with Hunter’s syndrome was to be subject to gene-editing to help him battle debilitating liver conditions. So, 2018, it was widely hoped, would be the year CRISPR would come to humans in a big way, with the first European and US clinical trials—to treat sickle-celled anaemia, beta thalassemia, etc—set to begin this year.
But findings of a Stanford study published in biorXiv, the pre-print server, should give pause to the euphoria that surrounds CRISP-Cas9. The study shows that many humans may already be immune to the most common forms of CRISPR-Cas9 used. The Cas9 protein—used in targeted editing of the genome—is a bacterial protein. Genome-editing researchers most commonly use Cas9 from bacteria that are already present in humans or routinely infect humans, and that means there is a high enough chance that most of us would have already developed an immune system response to Cas9. As per the Stanford study, 79% subjects showed immune response to Cas9 from Staphylococcus aureus and 65% to another bacterial Cas9 form, from Steptococcus pyogenes.
Which means, in many patients, CRISPR-Cas9 may be laid waste by the immune system, or worse, if it does manage to express in certain cells, it will cause the immune system to attack these cells and have serious health implications. However, given many alternative Cas9 protein sources can potentially become a part of the gene-editing picture and with many biotech giants pouring hundreds of millions of dollars into gene-editing research perhaps a way to side-step immune responses to Cas9.