A Danish study shows that CRISPR technology, which can cut and paste in genes, can be used to form circular DNA. This form of DNA can carry cancer genes, meaning that this new knowledge could be key to understanding how cancer occurs.

2018.09.06 | Helle Horskjær Hansen

Researchers from all over the world have begun using CRISPR technology which can easily and cheaply cut and paste in genes. CRISPR/Cas9 is a genetic tool that is often used in the treatment of certain human genetic diseases and also in a lot of basic research.

In science today, one of the hottest topics is the gene editing technology CRISPR, which makes it possible to cut out unwanted genes and paste new genes in instead. Now, as the first ever, researchers from Aarhus University and the University of Copenhagen have shown that it is possible to form circular DNA in cells by using gene scissors. The circular DNA carries cancer genes and approximately half of all cases of cancer are due to this DNA, which is formed based on our chromosomes.

"We’ve never previously been able to mimic cancer cells. In the long term, this research can be of crucial importance for the development of more effective medicine against cancer and for understanding the function of this circular DNA in the cell," explains Associate Professor Yonglun Luo from Aarhus University. He is behind the study, together with PhD Birgitte Regenberg and PhD Henrik Devitt Møller from the University of Copenhagen.

From healthy cell to cancer cell

The human genome consists of linear chromosomes. However, mutations occur in the DNA which can result in the formation of circular DNA elements, some of which can lead to cancer.

"By using the two gene scissors which are also known as CRISPR and Cas9 to cut simultaneously in the DNA in cells, we have discovered that there is a high risk of forming DNA circles," says Birgitte Regenberg.

Their findings have just been published in the international journal Nucleic Acids Research.

Until now, cancer researchers have lacked methods to form circular DNA and examine how a healthy cell becomes a cancer cell when a circle is formed. By cutting into a chromosome with CRISPR, researchers can now form a circular DNA in a healthy cell to learn more about their significance.

Poor DNA is common

"CRISPR is a welcome tool. In addition to cancer, we can also study how circular DNA otherwise affects our body. Earlier this year we showed that healthy people also carry circular DNA in the cells, but what circular DNA without cancer genes actually does is a subject we know very little about," says Birgitte Regenberg.

Researchers have recently shown that the circular DNA is common in people and have discovered that many types of DNA circles can have an impact on our cellular function.

"Hopefully, this study will create increased attention on the fact that the use of two gene scissors can actually lead to unintended DNA circle formations in cells. At the same time, we hope that the new knowledge will contribute to increased knowledge about DNA circles," explains Yonglun Luo.

About the result

Partners; PhD Henrik Devitt Møller, Institute of Biochemistry, ETH-Zurich, Switzerland and PhD Birgitte Regenberg, Section for Ecology and Evolution, Department of Biology, University of Copenhagen.

The research is supported by the Carlsberg Foundation, the Lundbeck Foundation and The Danish Council for Independent Research.

Associate Professor Yonglun Luo
Department of Biomedicine, Aarhus University
Tel.: (+45) 8716 7761
alun@biomed.au.dk

PhD Birgitte Regenberg
Section for Ecology and Evolution, Department of Biology, University of Copenhagen
Tel.: (+45) 3532 1680
bregenberg@bio.ku.dk

PhD Henrik Devitt Møller
Institute of Biochemistry, ETH-Zürich, Switzerland
Tel.: (+45) 2046 4438
henrik.moeller@bc.biol.ethz.ch