 Work to improve techniques for editing DNA, the code of life, has just seen an important new development at UC Berkeley. Researchers Bessem El-She'ib and Patrick Pausch have discovered Cas-Fi. It's a protein that may make the technique crisper, that has recently accelerated gene editing research, even more effective for treating genetic diseases in the future and improving agriculture. The team's discovery was sort of hiding in plain sight. We recently discovered these giant bacterial viruses, or huge phages as we call them. These viruses, we found them in many different environments from hot springs in Tibet, to baboons in Kenya, to moose in Alaska. They're found pretty much everywhere, and they have DNA that is up to 15 times larger than the average bacterial virus. I mean, it was mind-blowing to us to even find these to begin with, that they have such long strands of DNA, but also that they're found pretty much everywhere and went undetected for so long. Even more striking is that these viruses carry with them an unexpected and powerful ability. We found that they encode crisper-Cas systems, or an immune system that bacteria naturally use to fend off viruses. Bacteria keep a record of the viruses that infect them, and then they use a protein, to recognize and disable those viruses the next time they show up. Based on their discovery of this system, Berkeley scientists developed the crisper-Cas9 tool to locate and cut DNA at precise points. Now finding that a similar system exists in viruses themselves was stunning. Why in the world would a huge bacterial virus carry a system that kills viruses? And what we found is that this huge phage, or these giant bacterial viruses, will attach to the bacterial host and inject their DNA. That injected DNA contains a code prompting the host bacteria to make the protein Casphi. Casphi's job is to attack other competing viruses, this whole scenario orchestrated by the giant virus. So in a way it's protecting its host, but only because it wants to keep it and its resources to itself. Gene editing with the crisper system works this way. Scientists usually use the protein Cas9, pair it with an RNA sequence that matches the DNA sequence that needs to be changed. The RNA Cas9 pair locates the target DNA and cuts it with a chemical reaction. The cell then can repair its own DNA, or the correct DNA sequence can be inserted. But researchers found that the new protein they discovered, Casphi, is a lot smaller than Cas9, which might actually be an advantage for use in gene editing. So what's interesting is that we found this crisper-Cas5 system is about half the size of Cas9, and it can be used with a much smaller RNA strand to find its target and cut that target DNA. This could help alleviate one of the difficulties of using Cas9 to correct genetic diseases. Delivery is a key obstacle in trying to use this as a therapeutic. Because Cas9 is such a large protein, it has to be split up into different packages and you hope that they all reach the same address in the body to perform the therapy. Patrick, the co-first author of the paper, found that the protein is able to multi-task cut the targeting DNA, but also develop the guiding RNA system to locate the DNA to cut within one site in the protein, and that hasn't been seen before. Cas5 promises another practical advantage over Cas9. Some people seem to have antibodies that would reject the treatment, but with Cas5, because it comes from a bacterial virus and bacterial viruses aren't shown to cause this kind of allergic reaction in the body, we don't expect Cas5 to be rejected. The team looks forward to further testing of their new crisper-Cas5 system. We've shown that it can perform gene editing in human cells, but also in plant cells. It's very tiny, but it's mighty.