In a Nutshell: CRISPR Against Cancer

Imagine what we could do if we could reprogram our cells: We could correct what goes wrong in different diseases or counteract inherited weaknesses. Such a reprogramming tool was identified a few years ago and won the involved researchers Jennifer Doudna and Emmanuelle Charpentier a Nobel prize in 2020. The name of the underlying molecular machinery is CRISPR, and it is used to cut DNA at specific sites, to then reconnect the DNA, but to make that piece of DNA unusable in the process. Since its discovery, the method has been developed further to be used as a molecular therapeutic, and the first such therapeutic has just been approved in England. 
One of the major strengths of this new technology is however also a major concern: The DNA is permanently changed in the process. So, what if something goes wrong? What if the wrong piece of DNA gets cut? What if there are unintended long-term effects that cannot be undone? When both DNA copies of a gene are cut and gone, they are gone for good.
In a new article published in the journal Cell (Tieu et al., 2024), researchers have modified the original CRISPR approach: Instead of cutting DNA, they cut the RNA that serves as a messenger and template when proteins are made. The DNA remains unchanged, and as a result, all of the changes made are reversible.  This is a much safer way to reduce or eliminate the production of specific unwanted proteins.
In this work, the method was used to downregulate RNA in so-called T-cells of the immune system that are involved in the fight against tumor cells. T-cells that normally would show an exhaustion response to their permanent fight did much better when certain RNA molecules were cut and removed and the proteins were no longer made by the cells. As a result, tumors in mice treated this way shrunk more than in control mice.
The researchers showed that with the used technique they can downregulate up to 10 genes at a time and finetune protein production by switching the CRISPR tool on and off with an antibiotic. This mean, that they can optimize the tumor response by the T-cells. If this method proves feasible as medication, it is another step on the way towards a targeted and optimized cancer treatment.