UZH develops new compact gene scissors

A UZH research team led by Gerald Schwank from the Institute of Pharmacology and Toxicology, together with colleagues from the Swiss Federal Institute of Technology in Zurich, has further developed the gene scissors technology. It can repair genetic defects directly in the genome. Their new approach is based on the protein TnpB. It is significantly smaller than the CRISPR-Cas systems. These use Cas proteins. If you want to transport them to the right cells in the body, their size becomes a problem.

It was recently discovered that Cas proteins have evolved from much smaller proteins in evolutionary biology. TnpB, for example, is the precursor of Cas12. Current studies have therefore attempted to use these much smaller evolutionary precursors as genome editing tools. However, they work less efficiently than CRISPR-Cas. The team has solved this problem: "By engineering the small but powerful protein TnpB, we were able to develop a variant with which DNA can be modified 4.4 times more efficiently," Schwank is quoted as saying in a UZH press release.

"The trick was to modify the tool in two ways: First, to make it more efficient at getting to the cell nucleus, where the genome's DNA is located. And secondly, so that it also recognizes alternative gene sequences," says Kim Marquart, PhD student and first author of the study. An artificial intelligence model that the team developed together with UZH Professor Michael Krauthammer is able to predict "how well TnpB will work in different scenarios", Marquart continues.

In a mouse experiment, the team succeeded in using the TnpB tool to modify a gene that lowers cholesterol levels in patients with hypercholesterolemia by almost 80 percent. Now, according to Gerald Schwank, the aim is to "develop similar gene editing strategies in humans". ce/mm