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Knock-out pig clones advance transplant hopes

The piglets are genetically modified so their organs are less likely to be rejected when transplanted into humans

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鈥檚 immune system into launching an immediate attack.

Photo: PPL Therapeutics
Photo: PPL Therapeutics

鈥淭his advance provides a near-time solution for overcoming the shortage of human organs for transplants, as well as insulin-producing cells to cure diabetes,鈥 says David Ayares, vice president of research at PPL Therapeutics鈥 US division, where the pigs were created. 鈥淭his is the key gene for overcoming the early stage of rejection,鈥 he told 快猫短视频.

Several other teams are working on knocking out the same gene. One, led by researchers at the University of Missouri, is using a strain of pig that they believe will be more suitable for transplantation than the strain used by PPL. This team is expected to publish results of their cloning programme imminently.

Double knock out

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.

Human genes

鈥淭here will also be other genes we will incorporate into our program,鈥 Ayares says. 鈥淲e don鈥檛 think that one gene is going to produce an organ that鈥檚 going to be the end-all for transplantation. We鈥檙e going to have to add two to three human genes as well.鈥

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.

Other approaches to combating the human donor shortage have been successfully tried. Mechanical hearts are functioning in several patients. But creating artificial lungs and livers is much more difficult.

Stem cells, which can in theory be coaxed into forming any kind of cell in the body, have been transplanted into patients suffering the loss of a particular type of cell, for example.

鈥淏ut although a lot of the stem cell work is very exciting, we鈥檙e still very far off being able to grow an organ in a culture dish,鈥 says Julia Greenstein of Immerge BioTherapeutics in Charlestown, US, who is working on creating similar knock-out pigs with researchers at the University of Missouri.

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