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Cloned pigs

Five cloned piglets, genetically modified so that their organs are much less likely to be rejected by a human donor recipient, have been born in the US.

More than 62,000 people in the US alone are waiting to receive donated hearts, lungs, livers, kidneys and pancreases. The number of human donors falls far short of demand. Pig organs are of a similar size to human organs, and some scientists hope they might be used to help meet the shortfall. But previous attempts to transplant unaltered pig tissue into humans have failed, due to immune rejection of the tissue.

The five piglets, born on Christmas Day, lack a gene for an enzyme that adds a sugar to the surface of pig cells. The sugar would trigger a patient's immune system into launching an immediate attack.

"This advance provides a near-time solution for overcoming the shortage of human organs for transplants, as well as insulin-producing cells to cure diabetes," says David Ayares, vice president of research at PPL Therapeutics, US division, where the pigs were created. " This is the key gene for overcoming the early stage of rejection."
However, scientists warn that much more work is necessary before organs from copies of the pigs could be transplanted into humans. Human genes will need to be added, to prevent rejection of the organ in the long-term. There are also conerns that pig viruses could infect organ recipients.

Cloning techniques were vital to the production of the pigs. Genes can only be knocked out in a single cell. Cloning of these single cells then allowed the creation of a whole animal in which the gene was knocked out in every cell. But the PPL researchers have succeeded in knocking out only one copy of the gene for the enzyme, called alpha 1,3 galactosyl transferase. The team will now attempt to knock out both copies of the gene.

"There will also be other genes we will incorporate into our program," Ayares says. "We don't think that one gene is going to produce an organ that's going to be the end-all for transplantation. We're going to have to add two to three human genes as well."

The team will also conduct tests to investigate whether so-called porcine endogenous retroviruses (PERVS)from the pigs could infect human cells in culture. But Ayares hopes that organs created from PPL pigs could be transplanted into patients within five years.

"But although a lot of the stem cell work is very exciting, we're still very far off being able to grow an organ in a culture dish," says Julia Greenstein of Immerge Bio Therapeutics in Charlestown, US, who is working on creating similar knock-out pigs with researchers at the University of Missouri.

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