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The off-target effect of CRISPR technology has been solved.
The most controversial side effect of CRISPR gene editing technology-off-target effect has been solved. According to the report of Physicist Organization Network 12, the research team of Jennifer Dudner, one of the inventors of CRISPR-Cas9 technology, confirmed that anti-CRISPR protein can reduce the off-target effect caused by CRISPR by a quarter, and one protein named "AcrllA4" can even reduce the off-target effect by four times, while the gene editing of the target site is not affected in the whole process.
The Dudner laboratory of the University of California, Berkeley, cooperated with Jacob Cohen laboratory of the Institute of Innovative Genomics to study the anti-CRISPR protein discovered last year, and published a paper in the latest issue of Science Progress. They found that adding AcrllA4 protein can effectively reduce the off-target effect of CRISPR after several hours of gene editing when modifying the genetic variation related to sickle cell disease. The researchers explained: "Anti-CRISPR protein can mimic DNA and block Cas9' s ability to cut genes. The off-target effect will bring unexpected mutation, but our research proves that the off-target effect is completely controllable and not as serious as people think. "
In 20 16, the team of Joseph Band-Aid-Denumi, a scientist at the University of California, San Francisco, discovered four kinds of protein which can block the activity of CRISPR-Cas9 in Listeria, including AcrllA4 protein. Another team found three other protein species from meningitis bacteria. At that time, Band-Aid-Denumi predicted that these protein will become a standard part of gene therapy for CRISPR, so that CRISPR-Cas9 can "turn off its activity" after gene editing for a period of time, so as to prevent the off-target effect caused by random cutting at unnecessary sites.
Cohen believes that if the switch can only be turned on but not off, it will be very terrible, so the activity of turning off Cas9 is as important as turning it on. For the final therapeutic application of CRISPR, precise regulation of when and where Cas9 carries out gene editing and anti-CRISPR protein will play a crucial role.