They discover a new type of ‘genetic scissors’ that ‘locks’ viruses into infected cells

Bacteria and archaea are organisms formed by a single cell that, unlike ours, do not have a nucleus or internal membranous organelles. This can lead us to think that they are very simple beings and be tempted to ‘look’ down on them as a more complex form of life. However, they have spent millions of years perfecting a very sophisticated ‘autovaccine’ whereby a sort of ‘immune system’ remembers the DNA of the viruses that have infected the bacteria and, when reinfected, literally cuts off the aggression. This technique, called CRISPR by the Alicante scientist who discovered it, Francis Mujica, was turned into a revolutionary technology with which it is possible to easily and precisely modify any DNA, including human DNA. Now, American researchers have found a new type of ‘genetic scissors’ based on this tool that, in addition to cutting genetic material, slows down the growth of the infected cell and stops its spread. The results have just been published in two complementary studies (here and here) in the latest issue of the journal ‘Nature’. CRISPR uses a ribonucleic acid that acts as a guide for a protein (Cas) that kills the infection. The most famous protein or nuclease is Cas9, but to date others have been discovered, such as Cas10 or Cas12a, with other properties. In fact, the US team was exploring the possibilities of the CRISPR Cas12a system when they realized that a set of nucleases traditionally associated with this group worked differently not only from Cas12a, but from any other known CRISPR nuclease. This new type of CRISPR has been named CRISPR Cas12a2. Related News standard No Spanish scientists revive parts of bacteria from 2,600 million years ago that could cure genetic diseases Patricia Biosca standard No Why bacteria from the past are key to curing genetic diseases of the present Patricia Biosca The crucial difference lies in the mechanism of his defense action. When Cas12a2 recognizes the invasive RNA, the nuclease removes it. However, its work does not end there: it also damages other RNA and DNA within the infected cell, which affects its growth and limits the spread of the virus. In other words, it ‘closes’ the infection much more effectively. “This strategy was known in bacteria,” explains Oleg Dmytrenko, lead author of the first of the papers. Some other CRISPR-Cas systems work this way. However, a CRISPR-based defense mechanism that relies on a single nuclease to recognize the invader and degrade cellular DNA and RNA has not been observed before.” Cas12a2 recognizes target RNAs that are complementary to its guide RNA. Targeted RNA triggers collateral nucleic acid cleavage that degrades RNA, single-stranded DNA, and double-stranded DNA. “This activity leads to cell arrest, presumably by damaging the DNA and RNA in the cell, impairing its growth.” The authors point out that this new type of CRISPR could be used in molecular diagnosis and the direct detection of RNA biomarkers, which translates into new tests that reveal everything from viral diseases to cancer. The second study notes that Cas12a2 undergoes important structural changes after binding to its RNA target at various stages of the immune response. “Incredibly, Cas12a2 nucleases bend the usually straight piece of double-helix DNA 90 degrees, to force the backbone of the helix toward the enzymatic active site, where it cuts,” explains Thomson Hallmark, a biochemist at the University of Texas at Austin and one of the lead authors of the second study. “It is something extraordinary to observe, a phenomenon that makes other scientists look surprised.” MORE INFORMATION noticia No The astronauts of the international space station continue to be in danger: NASA is also studying their rescue noticia No Where to look to see C/2022 E3, a comet that will not be visible again for another 50,000 years For its part, his colleague Ryan Jackson, co-author of the same study, states that the difference between a healthy cell and a malignant or infected cell is genetic. “If Cas12a2 could be harnessed to identify, target, and kill cells at the genetic level, the potential therapeutic applications would be significant,” he says. We are only scratching the surface, but we believe that Cas12a2 could lead to additional and improved CRISPR technologies that will greatly benefit society.”