Cholesterol levels reduced by 80 percent: Zurich researchers develop more efficient gene scissors
The gene scissors Crispr-Cas are used worldwide to edit genes in the body. A team of researchers at the University of Zurich has now developed a new, more efficient version.
The gene scissors Crispr-Cas can be used to modify and repair DNA.
Bild: Getty
Around 1.2 million people in Switzerland have high cholesterol levels. Cholesterol in the blood is vital for the body’s metabolism, but there are types that have a positive effect on health and types that have a negative effect. Too much LDL cholesterol (low density lipoprotein) is bad.
This promotes arteriosclerosis and thus the risk of cardiovascular disease. The affected 15 percent of the population therefore take medication to lower their cholesterol levels. High cholesterol levels in the blood are usually hereditary and a healthy diet alone is not enough.
Zurich researchers developed a new gene scissors
Now researchers led by Gerald Schwank from the Institute of Pharmacology and Toxicology at the University of Zurich have developed a new method to combat this hereditary disease more effectively, as they report in a study published in Nature Methods. Study write. The gene scissors, the Crispr-Cas method, are used for this.
These gene scissors are used worldwide to edit, insert, delete or regulate genes in organisms. Cas proteins are the tools used to find a specific location in the genome and precisely change the genetic information. For example, a disease-causing mutation in the DNA can be restored to a healthy state.
The Cas proteins used, however, have the disadvantage that they are quite large. This makes it difficult to transport them to the right cells in the body. Researchers therefore tried to use the much smaller evolutionary precursors of the Cas proteins as a tool for gene scissors. The protein TnpB, a precursor of the Cas12 protein, was used for this purpose. The attempt was successful, but TnpB worked less efficiently.
The compact TnpB protein was modified
The Zurich researchers have now further developed the gene scissors by adapting and improving TnpB. This protein, which is found in bacteria and archaebacteria, has previously proven itself for genome editing in human cells, albeit with low efficiency and limited targeting accuracy.
The researchers therefore optimized TnpB so that the protein edits the DNA of mammalian cells more efficiently than the original Cas protein. The modified TnpB now changes the DNA more than four times more efficiently. At the same time, researchers at the University of Zurich used AI to develop a model that can predict how well TnpB will function in different scenarios, for example in the liver or brain.
The researchers also investigated whether the TnpB tool can be used to treat patients with familial hypercholesterolemia. They succeeded in modifying a gene that lowers cholesterol levels. In the treated mice, cholesterol levels were reduced by almost 80 percent.
“Lowering cholesterol through editing also lowers LDL cholesterol in healthy mice,” explains Schwank. It is also very likely that the newly developed gene scissors would have the same effect on humans. This has already been shown with the regular CRISPR gene scissors.
“We hope that companies will investigate its use in humans in the future,” says Schwank. “The classic CRISPR-Cas gene scissors use mRNA technology to deliver the gene scissors to the liver via lipid nanoparticles. This could also be used for TnpB.” This could effectively help people suffering from high cholesterol.
