The CRISPR-Cas9 molecule is used for gene therapies… But it could also be used to control the body’s immune response, which sometimes hinders the effectiveness of this treatment.
- The researchers deactivated a gene for a fixed period thanks to the CRISPR-Cas9 molecule.
- This technique helps prevent an exaggerated inflammatory response and severe tissue damage in the context of emerging infectious diseases.
A study could well revolutionize gene therapies. According to its authors, whose work has just been published in the journal Nature Cell Biology, the CRISPR-Cas9 molecule could make it possible to control the immune response of a mouse, during gene therapy. The latter is a therapeutic approach that consists of introducing genetic material into cells in order to cure a disease. In this case, CRISPR-Cas9 is used, in theory, to correct the faulty genes of the subjects studied, here animals. It cuts and replaces pieces of DNA from these genes so that they become healthy. But, quite often, the mouse immune system responds and prevents this modification by CRISPR-Cas9. So gene therapy doesn’t work.
Disable the gene that activates the immune response
The CRISPR-Cas9 genetic modification tool was discovered in 2012 by two researchers, Frenchwoman Emmanuelle Charpentier and American Jennifer Doudna. This technique has obtained many positive results in the laboratory, but still faces great difficulties. “Many clinical trials fail because of immune response against gene therapyexplains Samira Kiani, co-author of the study, in a press release. Then you can’t re-administer the drug because people have developed immunity.”.
This is why researchers at the University of Pittsburgh, in the United States, tested another function of CRISPR-Cas9: that which makes it possible to deactivate a gene for a fixed period. They modified CRISPR-Cas9 so that it binds to MyD88, the gene that activates the body’s immune response. Once MyD88 was deactivated in the mice, the scientists gave them the same gene therapy. This time it worked better since the mice’s immune system did not produce antibodies to stop it. Thus, the mice were more receptive to the treatment.
A technology that brings hope
“The ability to modulate the host immune response using this strategy is a promising step towards creating a universal yet targeted tool to prevent exaggerated inflammatory response and severe tissue damage in the context of emerging infectious diseases.”, say the authors of the study. In another of their research on mice, these same scientists were also able to regulate sepsis — or infection causing widespread inflammation — in these animals. But before Crispr-Cas9 is used outside the laboratory, for therapeutic purposes for example, this tool must be further improved and validated by clinical trials on humans. If these steps are quickly validated, CRISPR-Cas9 may be able to control some of the exaggerated inflammatory responses of Covid-19.
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