Nature sub-issue: New use of CRISPR solves the problem of gene therapy's vulnerability to failure.

To address this barrier, researchers at the University of Pittsburgh School of Medicine recently created a different CRISPR system.
the system briefly suppresses genes associated with the production of AAV antibodies, thereby suppressing the immune response and allowing viral vectors to deliver genes without obstruction.
results were published in the journal Nature's Nature Cell Biology.
"many clinical trials have failed because of the immune response to AAV gene therapy.
Samira Kiani, co-author of the study, said: "This treatment is not acceptable because it already has immunity to AAV.
"Considering that the gene that produces the relevant immune response is important for normal immune function, the researchers want to temporarily suppress the gene rather than turn it off permanently."
, they decided to use the genome editing tool CRISPR as a switch to regulate transcription, to inhibit the transcriptional activity of genes involved in the immune response.
"We used CRISPR for a double shot," said Dr. Mo Ebrahimkhani, one of the co-authors of the study.
" researchers used CRISPR-based systems to suppress endogenic myelin differentiation protein antigens (Myd88), reducing the host's ability to produce immunoglobulins for AAV.
in mice, when the animals were followed by AAV-mediated gene therapy, they did not produce more antiviral antibodies, resulting in better treatment than the control group.
addition to gene therapy, the study also showed that CRISPR-based immunosuppression could prevent or treat sepsis in mouse trials.
researchers note that the results highlight the potential of CRISPR tools for a wide range of inflammatory diseases, including cytokine storms and acute respiratory distress syndrome, both of which can suddenly appear in COVID-19 conditions, but more research is needed to verify their safety.
resources: s1. Editing the immune response can make gene therapy more effective, Retrieved September 6, 2020, from s2. Moghadam, et al. (2020). Synthetic immunomodulation with a CRISPR super-repressor in vivo. Nat Cell Biol 22, 1143-1154. Doi: 10.1038/s41556-020-0563-3.