The CRISPR tool is developing at an unprecedented pace into a powerful way of editing genes of bacteria, mammals, humans, plants, and even reptiles. In fact, it is also referred to as ‘genetic scissors.’ However, a new improvement can turn it into a genetic Swiss Army Knife. A research was conducted by Caltech that has improved the formula for helping the tool to zoom in on particular organs, tissues, or cell types. The research has also imparted enhanced control over what will happen next.
CRISPR has two main components; guide RNA molecules that can help in directing the tool to particular areas of the genome, and an enzyme that can then carry out the editing of the genes at that particular place. The most commonly used enzyme is Cas9, but other variations are also coming up, including Cas12a, Cas12b, and CasX. However, as useful as the CRISPR tool is; it is not perfect. Instead of focusing on the enzyme, the Caltech team focused on making improvements to the guide RNA.
The problem that they wanted to solve was that these molecules are ‘always on.’ This means that they are always seeking out their target regardless of where they are present in an organism. This could end up causing off-target mutations. The researchers on the latest study developed conditional guide RNAs (cgRNAs) that are not only more precise but also more powerful once they reach their target. These cgRNAs work like If/Then statements that are generally found in programming languages. The cgRNAs react to the presence or the absence of an RNA trigger, and they become inactive or active in response.
In practical terms, this implies that CRISPR can wait until it identifies a certain biomarker in a cell. This will lead it to either activating or silencing a gene for helping to treat that particular disease. The team has conducted tests of this technique in bacteria and was capable of showcasing both on/off and off/on logics. RNA triggers were able to switch cgRNAs off that started on while others were able to switch cgRNAs on that began as off.
Niles Pierce is the lead author of the study, and said, ‘There is still a long way to go to realize the potential of dynamic RNA nanotechnology for engineering programmable conditional regulation in living organisms, but these results with CRISPR/Cas9 in bacterial and mammalian cells provide a proof of principle that we can build on in seeking to provide biologists and doctors with powerful new tools.’