A new paper in Cell shows that it is possible (simple, really) to convert DNA-editing CRISPR proteins, such as Cas9, into RNA editors. All you have to do is delete a chunk of them. Deleting 55 amino acids from a DNA editor called IscB (the ancestor of Cas9) turned it into a “robust and versatile” RNA-guided RNA editor in human cells. This modified protein was used to cut mRNAs, knockdown gene expression levels, and even make an A-to-I base editor for RNA. There are existing RNA-editing proteins, of course, with Cas13 being the most commonly used. Cas13 uses a short snippet of RNA to seek out, and then cut, target RNA molecules. But it also has a major problem: After it cuts its target RNA, Cas13 causes “collateral damage” by also randomly chopping up nearby, bystander mRNAs. This is toxic to bacterial and mammalian cells. So in this paper, the authors deleted a part of the IscB protein (called the target-adjacent motif interaction domain, stretching from amino acids 433-487), which is normally responsible for its grabbing tightly onto DNA. And that deletion alone converted this protein into an RNA editor. The reason this works is because IscB naturally grabs onto both DNA and RNA, but is heavily biased toward DNA. So this deletion just removes its ability to grab onto DNA, thus biasing it to RNA. The resulting RNA editor is not only “more active than Cas13,” according to the paper, but it also “has no discernible cytotoxicity in human cells.” The author also show that the same exact approach works for other Cas proteins, including Cas9. Lots of gene editors can be converted into RNA editors, in other words. Good paper. Gene editors are even more versatile than we appreciated.