UZH Researchers Engineer TnpB into a Compact Gene Editing Tool

Researchers from the University of Zurich (UZH), led by Gerald Schwank from the Institute of Pharmacology and Toxicology, and ETH Zurich engineer TnpB to create a more compact gene editor for precise gene editing. Their study is part of their project aimed at using the TnpB tool to treat patients with familial hypercholesterolemia, a condition characterized by high levels of cholesterol in the blood.

CRISPR-Cas9 technology has been one of the widely used tools in gene editing. Due to the large size of Cas proteins, delivering these so-called gene scissors to specific cells in the body may be challenging for researchers. Recent studies have explored the use of smaller evolutionary progenitors, but these smaller versions function less efficiently.

UZH researchers, together with colleagues from ETH Zurich, addressed this challenge by engineering the protein TnpB that came from the bacterium Deinococcus radiodurans. Kim Marquart, PhD student in Gerald Schwank's laboratory and first author of the study, said that the tool was modified to efficiently go to the nucleus where the genomic DNA is located and to target alternative genome sequences.

In collaboration with the team of Michael Krauthammer, a professor at UZH, the research team created a new artificial intelligence model that can predict the efficiency of TnpB editing at any specific target site.  “Our model can predict how well TnpB will work in different scenarios, making it easier and faster to design successful gene editing experiments. Using these predictions, we achieved up to 75.3% efficiency in mouse livers and 65.9% in mouse brains,” Marquart said.

For more information, read the article from UZH and the study published in Nature methods.