Transgenic Pigs for Organ Transplants

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Transgenic Pigs for Organ Transplants

The rising shortage of donor organs has led scientists to genetically engineer animals that will produce organs suitable for transplant into humans. Pigs are well suited to the procedure because their organs are similar in size to a human’s, and they breed prolifically.

Human genes are inserted into the pig's DNA. The method most often used is microinjecting the genes directly into the nuclei of the fertilized eggs. The gene integrates itself into the animal’s genetic code at a single site, though multiple integrations are known to occur. If the gene fails to integrate before the later stages of cell cleavage in the embryo’s development, some cells will not carry the transgene. This is known as mosaicism.

The genes being inserted produce human decay accelerating factor (hDAF). This protein is found in human organs, and it prevents the body’s immune system from attacking the organ. Previous xenotransplants or organ donation among different species resulted in what is termed hyperacute rejection. The rejection of the organ occurred within minutes, which is too fast to be prevented by the immune suppressant drugs used in human to human organ transplants.

Pigs that undergo the genetic engineering procedure are known as founders, and are bred to produce more transgenic pigs. The resulting litters have to be homozygous for the transgene to produce the high levels of hDAF required for transplantable organs. Lines can be produced from homozygous founders, or by crossing heterozygous founders from different lines to produce “jigsaw pigs”. All pigs are tested to verify that they are homozygous for the transgene using florescence in situ hybridization (FISH).

Transplants of transgenic pig organs into primates such as monkeys and baboons have shown success. Further testing will have to be conducted before xenotransplants are approved for humans, however. Researchers are worried that porcine endogenous retroviruses (PERVs) may be transmitted to humans by the transplants. Pig DNA contains sections with virus-like qualities, and it has been proven these retroviruses can infect human cells.

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