Does Our Immune System React to CRISPR/Cas9?

Does Our Immune System React to CRISPR/Cas9?

Author: Marek Czykanski

CRISPR/Cas9 is considered a breakthrough for gene therapy. With the method, the DNA of living organisms can be changed easier and more targeted than ever before. Researchers have used it, e.g., to correct an Alzheimer’s mutation and the gene defect of sickle cell anemia in human cells. Meanwhile, the method is being tested in initial clinical trials.

However, it is still unclear if its use is safe in humans. Studies suggest that CRISPR/Cas9 may induce unwanted changes in the genetic material and its application could increase the risk of cancer. Dimitrios Wagner, Charité, Berlin, Germany, and colleagues have uncovered that also the immune system responds to it.

The most widely used Cas9 nuclease, SpCas9, originates from Streptococci pyogenes bacteria. Since humans often become infected with these bacteria, the researchers suspected that an immunological memory could exist against Cas9. They proved this by testing blood samples from healthy volunteers (24 women and 24 men between the ages of 18 and 60 years). In almost all volunteers the researchers could detect SpCas9-reactive T cells. In addition, they found that Cas molecules from other bacterial strains such as Staphylococci could also cause immune reactions. The scientists assume that this is due to the fact that the different enzymes are very similar.

If these results can be confirmed in studies with larger groups of volunteers, significant consequences are to be expected, as unwanted immune responses could compromise the safety and effectiveness of the method. The researchers offer possible solutions to overcome the problem: CRISPR/Cas9 can modify cells outside the body. The team has developed a pre-injection test that reliably shows that the risk of an immune reaction is low. For genetic disorders leading to defects in tissues that cannot be changed outside the body, the team is investigating the potential of regulatory T cells, which should control the unwanted immune reactions.

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