Inhibiting natural DNA repair processes increases the success of the DNA cut-and-paste technique CRISPR-Cas9. This is useful for scientific experiments, but may also have added value for future gene therapies. The chance of unwanted mutations decreases, which in theory makes the technique safer for use in humans. This is reported by the LUMC.
With CRISPR-Cas9, a very specific adjustment can be made in the DNA. Such as repairing mutations or adding a whole new gene. This revolutionary technique has turned science upside down. The possibilities seem virtually endless. In theory, hereditary diseases can be removed from human embryos. It is therefore not surprising that the development of this technique was accompanied by the necessary ethical discussions.
Until now, researchers mainly use this technique in the laboratory. For example, they can investigate the function of certain genes or the effect of a specific mutation. The clinical application of CRISPR-Cas9 is still lagging somewhat, partly due to the risk of mutations elsewhere in the DNA than for which CRISPR-Cas9 is used. The researchers have now found a solution.
“If we inhibit part of the natural DNA repair processes, the success of this technique will increase enormously,” says Joost Schimmel, researcher in Professor Marcel Tijsterman’s group. “Normally, no more than 5 percent of all cells contain the desired change after CRISPR-Cas9, and now the average is about 50 percent. We also see far fewer errors in other parts of the DNA.” This news spread like wildfire in the LUMC and more and more researchers are knocking on Schimmel’s door to learn more about this discovery. “Adding these inhibitors makes many CRISPR-Cas9 experiments in the lab easier, faster and more efficient.”
How does it work?
“Before CRISPR-Cas9 can make a specific adjustment in the DNA, it breaks both DNA strands in half,” explains Schimmel. “Normally, the cell wants to repair such a break as quickly as possible. This can be done in three ways.” Two of those three ways make a lot of mistakes during the gluing (NHEJ) and knitting (TMEJ) of the DNA strands, leading to mutations. By blocking these two repair processes, only space is left for the error-free recovery process.
By: National Care Guide