With DNA editing, Brazilians are making headway in transplanting pig organs to humans – 03/31/2021 – Science

Using DNA editing techniques, Brazilian researchers have taken important steps to enable the transplantation of pig organs to humans.

They were able to remove bits of genetic material that could cause rejection or disease in patients given tissue from pigs. The first goal is to conduct kidney transplants, which could significantly reduce the transplant queue and patient reliance on constant hemodialysis sessions.

The work is coordinated by geneticist Mayana Zatz and doctor Silvano Raia from USP. “We were very successful on the molecular side,” says Zatz.

“In this way modified pig kidney transplants for baboons [que são primatas, como o ser humano] have already shown that long-term survival is possible. The monkeys had kidneys for two and a half years and were euthanized as part of the study, regardless of the transplant. The procedure has not yet been done on human patients around the world, but there are teams working for it and it’s an effort that needs to be done in Brazil too, ”she argues.

Pigs have long been considered a promising source of this type of xenotransplantation (transplantation between species). Both the size of the animals and their anatomy are compatible with the needs of human receptors.

For the transplant to be viable, two types of genetic modification are considered necessary. The first is to remove three sections of pig DNA that would result in acute rejection in patients. In addition, it is necessary to eradicate regions of the genome known as pervs (English acronym for “endogenous porcine retroviruses”).

Essentially, these are “fossilized” viruses that infected today’s pig ancestors and inserted versions of their genetic material into the animals’ genome. It is what the AIDS virus is still doing to the people it infects today.

In animal organisms, the pervs are harmless, but there is a risk that they will “resurrect” and infect another species that will receive the transplanted organ. For both rejection genes and pervs, the team has already mastered the methods of deleting those genes using the DNA manipulation technique known as crispr (pronounced “crísper”).

The next step, says Silvano Raia, will be to transfer the nucleus of the modified pig cells to eggs whose nucleus has been removed – in practice a cloning process – and to implant the embryo thus created in women. The kidneys of puppies born from this process are tested in cardiopulmonary bypass systems to show that they are able to properly perform the organ’s filtering function.

However, this will still not be enough for research to reach clinical test with patients. To this end, the researchers are looking for funds to build the so-called “pig factory”, a facility in which the pigs are raised under sterile conditions and are therefore safe for transplantation. The area is now available: an area of ​​1,100 m2 made available by the Ipen (Institute for Energy and Nuclear Research) in the capital São Paulo. “With the ‘pig factory’ we could start testing patients every six months to a year,” says Zatz.

Raia lists the bioethical requirements for the selection of participants: They would be people whose life expectancy would be higher with the transplant than with just continuing hemodialysis. In addition, they would be given priority in the human organ transplant queue if the procedure didn’t work. “It would be possible to perform a xenograft without removing the still functioning kidney from the patient, which makes it reversible in the event of a problem,” he explains.

The researchers even consulted religious authorities – Catholic, Jewish, and Muslim – to determine their usefulness to the process. “Essentially, anyone can do it,” says Raia.

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