Zurich researchers develop small gene-editing scissors

Zurich researchers overcome efficiency hurdle of compact gene scissors Keystone-SDA

Zurich researchers have developed new gene scissors that are much smaller than the familiar Crispr gene scissors and can therefore be transported more easily to the genetic material in cells.

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Attempts to create a more compact version of CRISPR gene scissors has been difficult. To date, small alternatives have functioned less efficiently the University of Zurich (UZH) explained in a press release on Monday. Zurich researchers have now overcome this hurdle with improvements to the mini gene scissors. The researchers presented the technology in a study published on Monday in the scientific journal Nature Methods.

CRISPR-Cas technology has revolutionised medicine, biotechnology and agriculture. In 2020, researchers Emmanuelle Charpentier and Jennifer Doudna received a Nobel Prize for their discovery of the technology. The tools can be programmed to find a specific location in the DNA and modify the genetic information. This makes it possible to restore a disease-causing mutation in the DNA to a healthy state.

However, these CRISPR-Cas gene scissors are relatively bulky, as study author, Kim Marquart, explained to the Keystone-SDA news agency. According to the researcher, this bulkiness poses a challenge for efficient transport into the cells in which the genetic material is located.

Researchers have recently been trying to use the much smaller evolutionary ancestor of the Cas12 protein, the TnpB protein, as gene scissors. The compact TnpB protein has already proven its worth for genome editing in human cells, albeit with low efficiency and limited accuracy, according to the UZH.

The researchers from the University of Zurich, in partnership with the Swiss technology institute ETH Zurich, optimised TnpB so that it edits the DNA of mammalian cells more efficiently than the original protein. They successfully used this in an initial test on mice.

“We were able to edit a gene that regulates cholesterol levels, thereby reducing the cholesterol in treated mice by nearly 80%,” says Gerald Schwank, who led the research team. “The goal is to develop similar gene editing strategies in humans in order to treat patients suffering from hypercholesterolemia.”

Translated from German by DeepL/jdp

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