Researchers from Aarhus University have developed a new CRISPR based method that can temporarily turn a gene up and down without altering its DNA. The method enables them to study the effect of genes in cells and their role in the development of diseases. The results have been published in the scientific journal Genome Research.

2021.09.13 | Helle Horskjær Hansen

When biomedical researchers cut and paste in genes – with what is called CRISPR technology or the catchier gene scissors – they typically do this by removing a gene permanently or adding more copies of the gene. Researchers from Aarhus University have now developed a CRISPR-based method whereby they do not need to change the DNA of the gene, but only briefly adjust its activity. According to the researcher, this gives a more natural form of genetic manipulation.

"We adjust the activity of the gene for a few days, and this gives us the opportunity to study its natural function in cells and its role in a disease context," says associate professor Rasmus O. Bak, whose research group is behind the study.

In the laboratory, researchers often use cancer cells in studies of genetic function, as these are very robust and easy to work with. However, these cancer cells are not always optimal for representing the type of tissue that the researcher is interested in, and the cancer cells also often carry many defects that can blur the true function of a gene.

The same technology as vaccines against Covid-19

"Our study shows that we can take cells from a blood sample and carry out a very effective regulation of a gene in blood cells, which is historically something that’s been extremely difficult to do. We can now do this in a very effective and fast way, and as these cells come directly from an individual, studying genetic function in these cells is far more relevant," he says.

The method is based on the same technology as the new vaccines against COVID-19 (mRNA technology), which can be delivered very effectively to these more sophisticated cell types such as e.g. blood cells that are taken directly from a person. At the same time, the technology is far less harmful to cells than existing technologies, which means that the cells maintain their characteristics after the genetic regulation. 

"We now have a much better method of investigating gene function, and we’ve even shown that we can regulate several genes at the same time. The method is extremely easy to implement in a laboratory, and we already have several collaborative partners from universities in USA, Israel, Sweden, Austria and Denmark, who’ve been surprised by how effective and applicable the technology is," says Rasmus O. Bak.

At the same time, the research results show that the technology can be used to direct stem cells to develop into specific types of blood cell. According to the researcher, it will in the future be possible to use the method to develop cell therapies, whereby cells can be assigned new characteristics using the technology.

"Because genes’ activity controls the development and function of cells, we expect it to be possible in the longer term to also utilise the technology in new forms of cell therapy, where patients are treated with disease-fighting cells, which are optimised with specific genetic activity."

Background for the results

• The scientific article can be read in Genome Research
• The study is basic research.
• Researchers at the Medical University of Graz, Austria, are partners in the study.
• The study is financed by the Lundbeck Foundation, the Novo Nordisk Foundation and the Innovation Fund Denmark.

Contact

PhD, Associate Professor Rasmus O. Bak
Aarhus University, Department of Biomedicine
bak@biomed.au.dk
Mobile: (+45) 9392 9100