One step closer to using pigs as organ donors for humans

Researchers are now one step closer to being able to transplant organs from pigs into human beings. They have switched off some viral genes in the pigs' DNA that would otherwise have been an obstacle to using pigs as organ donors.

"By switching off the viral genes we have eliminated the risk of the virus being transmitted from pig organs to humans after a transplant. This has been a major medical problem which we have been forced to resolve to make it possible to use organs from pigs in humans," explains one of the researchers behind the study, associate professor at the Department of Biomedicine at Aarhus University, Yonglun Luo.

The new research results have just been published in the scientific journal Science.

Yonglun Luo sees major perspectives in the breakthrough, one being the fact that there are far too few organ donors in Denmark. Last year, 29 people died in Denmark while on the waiting list for a new organ, and more than 400 are currently waiting to receive an organ from a donor.

"We have solved the problem by switching off the viral DNA in the pigs, so that the virus can no longer copy itself and infect humans. This was necessary because we will never use organs from pigs in humans if this also means we are transferring lots of diseases," explains Yonglun Luo.

First time in living pigs
In the new research, the researchers have used both cloning techniques and genetic manipulation techniques to create pigs that do not have functional viral DNA in their genome.

The researchers began by taking some pig cells and introducing into them with the genetic manipulation tool CRISPR to destroy all the retroviral genes, so that the viruses could not make more copies of themselves. The researchers then placed the cells in eggs and inserted these eggs in sows to end up with living pigs.

The eggs developed into piglets inside the uterus of the sows, and after birth the researchers examined them and see that they no longer had functional viral DNA in their genome. It is thus possible to use organs from these pigs in human beings without the risk of dangerous viruses also following.

"Researchers have previously created cells where they have inactivated all the retroviral genes, but this is the first time this happens in living pigs," explains Yonglun Luo.

Even though the researchers have solved the problem of viral DNA, they still need to resolve the immunological problem whereby the human body will reject organs from pigs, as the immune system will see them as something alien that needs to be combated.

Yonglun Luo explains that to do this, as well as the already modified viral genes, they will also have to modify at least 28 other genes which are responsible for ensuring that organs from pigs are not compatible with humans.

This is also an area where the researchers will use CRISPR technology to alter genes. The plan is then to attempt to transplant organs from pigs into primates and see if they work as they should.

"It will take some years before major and complex organs from pigs such as the heart and liver can be used in human beings. But to begin with, we can use smaller organs such as skin and corneas from pigs," explains Yonglun Luo.

The research results – more information

• The study is basic research.
• The work is the result of a collaboration between Aarhus University and Harvard Medical School, Professor George M. Church’s group and research groups in China.
• The project is financed by the Danish Council for Independent Research and Sapere Aude.
• The scientific article "Inactivation of porcine endogenous retrovirus in pigs using CRISPR-Cas9" is published in Science.

Contact

Professor Thomas G. Jensen
Aarhus University, Department of Biomedicine
Mobile: (+45) 2778 2805
Email: thomas@biomed.au.dk

Associate professor Yonglun Luo (contactable from 15 August)
Aarhus University, Department of Biomedicine
Telephone: (+45) 8716 7761
Email: alun@biomed.au.dk