“Gene editing to remove viruses brings transplant organs from pigs a step closer,” The Guardian reports after researchers used the new CRIPSR gene editing technique. CRIPSR acts like a set of molecular scissors that can cut out potentially harmful infectious genes.
Despite the difference in size and shape, many of the pig’s internal organs are remarkably similar to human organs, making them a candidate for organ donations. The drawback is that some pigs carry what are known as porcine endogenous retroviruses (PERVs).
Retroviruses are a group of viruses that can cause various cancers and immunodeficiency illnesses. The retroviral group includes the human immunodeficiency virus (HIV) that affects humans. This has been found to make any attempt using “unedited” pig cells for donation unsafe.
The researchers showed that they could use CRIPSR to target the areas of the pig DNA that were carrying the retroviral code. Using this technique they were able to successfully remove all retroviruses from the pig cells.
These gene-edited cells were used to create pig embryos, which were then implanted into surrogate sows. The resulting piglets were free from PERVs.
This research is a promising step forward in the possible use of pig organs to meet the massive shortage of human organ donors. However, there are many more stages of research to go and there are likely to be other practical, ethical and safety issues to overcome before considering pigs as organ donors.
Until further progress is made you can help by signing up to the NHS Organ Donation register. You can do this online and it takes just a few minutes.
The study was carried out by researchers from eGenesis Inc in the US, Zhejiang University, China, and other institutions in China, the US and Denmark. The study was mainly funded by eGenesis Inc. and the US National Institute of Health, with other funding grants awarded to individual researchers.
eGenesis Inc is a US biotech firm working on trying to make animal-to-human organ transplant safe and effective. This technique is known as xenotransplantation.
The study was published in the peer-reviewed journal Science.
The UK media give balanced coverage of this research by making it clear there were a number of hurdles to be cleared before xenotransplantation could become a reality.
This laboratory study aimed to see whether it was possible to remove porcine (pig) retroviruses, which can infect human cells, from genetically modified pigs.
Retroviruses are a group of viruses that carry their genetic material in ribonucleic acid (RNA) and are named because of the enzyme reverse transcriptase that transforms RNA into DNA. The retrovirus group can cause various cancers, neurodegenerative disorders, and notoriously HIV.
Pigs show potential as organ donors for humans as their organs are similar in size and function and can be bred in large numbers. Porcine retroviruses (PERVs) are currently one of the big safety barriers preventing us using pigs as organ donors.
The researchers first demonstrated that porcine retroviruses are transferred to human cells. They transferred pig epithelial cells (that line organs and other surfaces in the body) to human embryonic kidney cells. When the human embryonic cells (cells derived from embryos developed from eggs fertilised in the lab) were monitored for four months, the number of porcine retroviruses increased over time. They showed that these viruses had integrated into the human DNA and could be transmitted to other human cells.
The researchers then showed they were able to inactivate all 62 copies of porcine retroviruses from the pig epithelial cells, which safely eliminated virus transmission to the human embryonic cells.
The focus of the current study was to demonstrate that they could achieve the same results and inactivate porcine retroviruses from pig foetal fibroblast (connective tissue) cells.
Firstly they mapped the 25 viruses present in the genetic code of these cells. They then used the technique of “CRISPR Guide RNA” which guides enzymes to cut the DNA at specific locations, effectively editing out the genes carrying the virus.
With some modifications to the CRISPR Guide RNA technique, the researchers were eventually able to completely edit out of all retroviruses from the pig fibroblast cells. They also confirmed that the technique did not lead to unwanted alterations elsewhere in the DNA.
They then used these gene-edited fibroblasts to create pig embryos (using a technique called somatic cell nuclear transfer, SCNT). After confirming the resulting embryos were completely free from retroviruses, they were then transferred to surrogate sows .
From about 200-330 embryos per sow transferred across to 17 sows, they produced 37 piglets, of which 15 remained alive up to four months. The piglets from successful pregnancies were confirmed to have no retroviruses in their DNA. They also confirmed there weren’t any abnormal structural changes to these piglets.
The researchers are continuing to monitor the longer term effects in these animals.
The researchers conclude that they have shown porcine retroviruses can be passed from pig to human cells in the laboratory, highlighting “the risk of cross-species viral transmission in the context of xenotransplantation”.
To work towards eliminating this risk, they used a technique called CRISPR Guide RNA to produce pig embryos, foetuses and live pigs free from the retroviruses.
This promising research shows that it can be possible to use gene editing techniques to eliminate retroviruses from pigs, removing one of the potential barriers to using genetically modified pigs as organ donors for humans.
There are a few points to note. As the researchers say, though they have shown that pig retroviruses can be passed onto human cells in the laboratory, we don’t know what the effects would be in real life. We don’t know whether pig retroviruses would be transferred to humans and whether they could cause cancers or immunodeficiency illnesses, for example.
The research is at an early stage. The study has shown that they can produce retrovirus-free piglets but moving onto pig organ donation is another step. While some pig tissues have been in medical use for decades, such as pig heart valves and insulin, there are likely to be various practical, ethical and safety steps to overcome when it comes to transplanting whole large animal organs into humans.
Various experts have given their response to the news – both highlighting the positives and negatives.
Prof Darren Griffin, Professor of Genetics, University of Kent, says: “This represents a significant step forward towards the possibility of making xenotransplantation a reality,” while Prof Ian McConnell, Emeritus Professor of Veterinary Science, University of Cambridge, cautions: “[Organ transplant] is a huge unmet need of modern medicine. But the use of animal organs such as pig kidneys and hearts is not without serious ethical and biosecurity concerns.”
When it comes to organ donation, demand far up outstrips the supply in the UK. You can help with this problem by signing up to the NHS Organ Donation register.