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Friday 22 September 2017

Pig organs could soon be used for human transplants

Growing human transplant organs in pigs has become a more realistic prospect (Stock image)
Growing human transplant organs in pigs has become a more realistic prospect (Stock image)

John von Radowitz

Growing human transplant organs in pigs has become a more realistic prospect after scientists used advanced gene editing to remove threatening viruses from the animals' DNA.

Porcine endogenous retroviruses (Pervs) are permanently embedded in the pig genome but research has shown they can infect human cells, posing a potential hazard.

The existence of Pervs has been a major stumbling block preventing the development of genetically engineered pigs to provide kidneys and other organs for transplant into human patients.

That hurdle may now have been cleared away, according to new research reported in the journal Science.

Researchers in the US used the precision gene editing tool Crispr-Cas9 combined with gene repair technology to deactivate 100% of Pervs in a line of pig cells.

Piglets cloned from the fibroblast (connective tissue) cells turned out to be Perv-free.

Dr Luhan Yang, co-founder and chief scientific officer at the biotech company eGenesis, said: "This is the first publication to report on Perv-free pig production.

"We generated a protocol to enable multiplex genome editing, eradicated all Perv activity using Crispr technology in cloneable primary porcine fibroblasts and successfully produced Perv-free piglets.

"This research represents an important advance in addressing safety concerns about cross-species viral transmission.

"Our team will further engineer the Perv-free pig strain to deliver safe and effective xenotransplantation."

The scientists first mapped the Pervs present in the pig genome, identifying 25 in total.

Tests demonstrated that pig cells could infect human cells with Pervs in the laboratory. The viruses could then be transmitted to other cells not exposed to pig tissue.

Whether or not Pervs would actually cause diseases in humans is unknown, but they are considered an unacceptable risk.

Other endogenous retroviruses (ERVs) in humans have been suggested to play a role in cancers and autoimmune disorders, although evidence for this is lacking. Their involvement in multiple sclerosis and motor neurone disease has also been proposed.

British expert Professor Ian McConnell, from Cambridge University, said the research was a "promising first step".

He added: "Successful transplantation of tissues and organs from animals to man, known as xenotransplantation, has been one of the goals of modern medicine for the last 20 years.

"The safe use of pig organs such as kidneys in xenotransplantation has been seen as an approach which could be used to overcome the shortage of donor organs in human transplantation.

"The problem is that all pig cells carry cancer viruses embedded in their DNA. These are known as endogenous retroviruses which, although normally silent, can be activated to become fully infectious for human cells when pig cells carrying these retroviruses are co-incubated with human cells.

"Since xenotransplantation involves long-term intimate cell-to-cell contact the potential for the species jump of retroviruses for the entire life-time of the transplants is a very real one."

Genetics expert Professor Darren Griffin, from the University of Kent, said: "This represents a significant step forward towards the possibility of making xenotransplantation a reality.

"The chance of transmitting Perv from the pig organ to the human cells was a significant barrier and the study shows yet another application of the Crispr-Cas9 system."

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