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The American company’s attempt to transplant the hearts of genetically modified pigs into human babies

Agensys, a company based in Cambridge, Massachusetts, has developed a technique that uses the CRISPR gene-editing tool to make about 70 edits to the pig genome. According to the company’s team, these modifications should allow the organs to be successfully transplanted into humans. In order to pave the way, Agenesis transplanted the heart of a genetically modified immature pig into a baby baboon.

to report MIT Technology ReviewAgensys hopes to be able to transplant pig hearts into babies with serious heart defects as soon as next year. The company’s goal is to buy babies more time to wait for a human heart. Before achieving this goal, the company will try pig heart transplants on 12 baby baboons. So far, two such operations have been carried out; But none of the animals survived more than a few days.

However, Agensys, like other companies active in the field of organ transplantation, remains optimistic. Many recipients of the first liver transplants did not survive, says Robert Montgomery, director of the Transplant Institute at New York’s Langone Hospital; But since then, thousands of people have benefited from such links.

The risk of genome modification

In America, more than 100,000 people are waiting for an organ transplant, and almost 17 of them die every day. Researchers are investigating various options, including the possibility of bioprinting organs or growing new organs in people’s bodies. Animal organ transplantation is another potential alternative to help meet the need for organs.

The idea of ​​using animal organs and tissues, which is known as external transplantation, is an old solution and the first related experiments were carried out in the 17th century. Most of the recent efforts in this field were made in the 1960s and then in the 1990s. In many of these efforts, the organs of monkeys and baboons were used; But researchers agreed by the early 1990s that pigs were the best possible candidates for organ donation, Montgomery said.

Primates have a high value; They are intelligent animals that experience complex emotions. These mammals reproduce slowly and only a small number of them can be used for human research. It is also more likely that primates can transmit harmful viruses to us. On the other hand, humans currently know a lot about raising pigs, and their organs are almost as big as ours.

However, transferring organs between animals of different species is not an easy task. Even organs from another human may be rejected by the immune system. On the other hand, animal tissues have many more components that our immune system considers “foreign”. This may cause the transplanted organ to be attacked by the immune system. For example, it is possible to transmit the virus with organs. Even if the donor animal is not infected, it will carry the genetic codes for ancient viruses called “endogenous retroviruses” that have been integrated into the animal’s DNA long ago.

Endogenous retroviruses do not cause problems for the host animal; But there is a possibility that they can cause infection in other species. Chris Gyngell, a bioethicist at the Murdoch Children’s Research Institute in Melbourne, Australia, said: “There is a risk that viruses native to animals will evolve and become lethal in humans.”

The Agenesis research team uses the CRISPR gene editing tool to counter this risk. Using CRISPR-Cas9, 50 to 70 copies of retroviruses can be inactivated in the genome, says Mike Curtis, the company’s president and CEO. These edits will prevent viruses from multiplying.

In order to make pig organs safe for humans, Agenesis scientists are also doing other gene editing; For example, several cases to eliminate genes that cause pig protein products to lead to harmful immune responses in humans. The researchers also insert 7 human genes into the pig’s organ to reduce the possibility of the organ being rejected by the recipient’s immune system.

The research team conducted their experiments on cells in the connective tissue of pigs called fibroblasts. The researchers then take the nuclei containing the DNA of the edited cells and insert them into pig egg cells. After fertilization of the egg with sperm, the resulting embryo is implanted in the uterus of an adult pig. Finally, the simulated pigs are born by caesarean section. “This is the same technology used in the ’90s to clone Dolly,” says Curtis, referring to the famous sheep that was the first animal cloned from an adult cell.

Agenesis has about 400 cloned pigs at a research facility in the Midwest. The company does not want to disclose the exact location of this research center; Because his facilities have been targeted by animal rights protesters. Early last year, Agenesis launched a “clean” center for the production of suitable human organs. Anyone entering the facility must shower and wear protective clothing. This is done to prevent the entry of insects that may infect the pigs. Currently, 200 pigs are kept in groups of 15 to 25 in this center.

According to Curtis, the pigs whose organs are ultimately not used will be studied closely; Because the company needs to know what effect the numerous gene editing will have on the animal throughout its life. The research team also wants to find out whether human genes are expressed over time. According to Curtis, some of the pigs are more than 4 years old and so far so good.


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