Xenografts on the threshold
Organs of GM pigs will begin to be transplanted to people in the coming years
Sergey Kolenov, Hi-tech+
Xenotransplantology has emerged from a long streak of failures. Thanks to gene editing, animal organs can now be modified so that they fit humans. The first clinical trials will start in the near future.
The shortage of donor organs has become a serious problem of transplantation. In the USA alone, 20 people die every day who did not wait for their turn for transplantation. There are several suggestions on how to solve it: from growing organs from stem cells to replacing them with artificial analogues.
Perhaps the most realistic of them is xenotransplantation, that is, the transplantation of organs from other animals to humans. And the most likely candidate for the role of a donor is a domestic pig.
Despite the fact that the evolutionary lines of humans and pigs diverged about 90 million years ago, internally we are very similar. In addition, unlike our closest relatives, the great apes, pigs multiply rapidly and are not endangered. The difficulty is that it is impossible to simply transplant a pig's heart or liver to a person: they will be rejected by the immune system.
So far, attempts to combine the organ of a pig or another animal with the human body have failed. For example, in 1984, surgeon Leonard Bailey transplanted a baboon heart to a newborn girl – but after the operation, the child lived less than three weeks.
The only exceptions are minor operations, such as heart valve replacement. But today there has been significant progress in xenotransplantology, notes New York Times. Back in 2013, Harvard researcher Luan Yang proved that using CRISPR technology it is possible to make pig organs more suitable for transplantation to humans. For example, to cut out endogenous viruses scattered throughout the genome of these animals and potentially dangerous to the recipient. And now scientists are getting closer to it.
A pig named Laika
Gathering a team of like-minded people, Yang, together with her supervisor George Church, founded the biotechnology company eGenesis, which quickly raised $38 million in investments. However, to completely remove all 62 copies of the virus, the technology had to be improved for another two years. After the method was tested on tissues in a Petri dish, eGenesis created the first live pig whose genome was completely cleared of endovirus. She was named Laika – in honor of the first dog to fly into space.
Having dealt with the endovirus, Yang's team now wants to use CRISPR to inject several dozen human genes into pig DNA. They will confuse the immune system and reduce the risk of blood clots.
Against the background of the successes of Luan Yang and other scientists, a number of startups have appeared that intend to make xenotransplantation commercially attractive. For example, United Therapeutics promises to produce hundreds of organs a day. Employees of its subsidiary Revivicor transplanted a pig's heart to a baboon – and it beat regularly for 945 days. In the last two years, several more successful experiments on xenotransplantation of organs to monkeys have been conducted, and now the researchers intend to move on to clinical trials in humans.
For example, this month in Boston, a person will be transplanted pig skin for the first time. In addition, an experiment is planned, the participants of which will receive genetically edited pork kidneys.
If the kidneys don't work, patients will simply return to dialysis. If successful, they will have to take immunosuppressants so that foreign organs will take root.
The immunologist David Sachs wants to solve this problem, who is looking for a different, non-drug way to restrain the immune response. He is conducting research on an experimental herd of 100 pigs on a specially equipped farm in Massachusetts. The ancestors of these animals are feral pigs from Andean and Rocky Mountains, smaller and hardier than their domestic relatives.
The goal of working with these pigs is to obtain genetically homogeneous animals that will become a model for studying immune tolerance. Scientists will transplant part of the patient's bone marrow and stem cells to them before surgery to mix the two immune systems. When transplanting from person to person, the technique allows you to reduce the immune response. The researchers hope that it will also work with xenotransplantation.
Not every pig is suitable for human organ transplantation. Researchers from The University of Alabama at Birmingham (USA) has developed a test that detects the presence of infections in animals. This will allow only healthy animals to be selected for transplantation.
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