Gene therapy against clostridium
CRISPR destroys the causative agent of colitis in mice
Svetlana Maslova, Hi-tech+
Scientists applied targeted effects on the bacterium using CRISPR/Cas3 gene editing technology and were able to suppress the pathogen without harm to other intestinal bacteria. This opens up new possibilities for the treatment of colitis, which returns in every third patient after a powerful antibiotic exposure.
American scientists from North Carolina State University has shown that CRISPR/Cas3 can cope with the destruction of Clostridioides difficile – a pathogen that causes the development of pseudomembranous colitis. Colitis is an inflammatory disease of the colon. Frequent use of antibiotics is considered to be the main risk factor for the development of C.difficile.
Article by Fletcher et al. In Vivo Targeting of Clostridioides difficile Using Phage-Delivered CRISPR-Cas3 Antimicrobials is published in the journal mBio – VM.
The main goal of the scientists was the targeted destruction of C.difficile without harm to other intestinal microorganisms. Experiments have shown that using genetically modified bacteriophages ϕCD24-2, the CRISPR/Cas3 method effectively removes and replaces certain sequences of the genetic code in bacteria.
"We needed to target the pathogen without destroying the rest of the microbiota. And it succeeded," said study co–author Casey Therio.
The use of CRISPR/Cas3 in mouse models reduced the levels of C.difficile, but the process did not last long. Two days later, the concentration of the pathogen increased again, but even the preliminary results were highly appreciated by scientists.
"We have received the first positive result in the long process of developing strategies for the treatment of colitis. The use of CRISPR/Cas3 opens up new opportunities for other infectious diseases," the authors commented.
Now the team will refine the method to prevent the return of C.difficile. In people with colitis caused by C.difficile, about 30% of cases of relapse occur after treatment with standard antibiotics. In the future, the use of CRISPR will help treat the disease without serious side effects for the intestinal microbiota.
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