This company plans to transplant pig hearts into babies next year

The baby baboon is wearing a mesh gown and appears to be sitting upright. “This little lady … looks pretty philosophical, I would say,” says Eli Katz, who is showing me the image over a Zoom call.

This baboon is the first to receive a heart transplant from a young gene-edited pig as part of a study that should pave the way for similar transplants in human babies, says Katz, chief medical officer at the biotech company eGenesis.

The company, based in Cambridge, Massachusetts, has developed a technique that uses the gene-editing tool CRISPR to make around 70 edits to a pig’s genome. These edits should allow the organs to be successfully transplanted into people, the team says. As soon as next year, eGenesis hopes to transplant pig hearts into babies with serious heart defects. The goal is to buy them more time to wait for a human heart.

Before that happens, the team at eGenesis will practice on 12 infant baboons. Two such surgeries have been performed so far. Neither animal survived beyond a matter of days.

But the company is optimistic, as are others in the field. Many recipients of the first liver transplants didn’t survive either—but thousands of people have since benefited from such transplants, says Robert Montgomery, director of the NYU Langone Transplant Institute, who has worked with rival company United Therapeutics. Babies born with heart conditions represent “a great population to be focusing on,” he says, “because so many of them die.”

Editing risk

Over 100,000 people in the US alone are waiting for an organ transplant. Every day, around 17 of them die. Researchers are exploring multiple options, including the possibility of bioprinting organs or growing new ones inside people’s bodies. Transplanting animal organs is another potential alternative to help meet the need.

The idea of using organs and tissues from animals, known as xenotransplantation, is an old one—the first experiments were performed back in the 17th century. More recent attempts were made in the 1960s, and again in the 1990s. Many of these used organs from monkeys and baboons. But toward the start of the 1990s, a consensus emerged that pigs were the best donor candidates, says Montgomery.

Primates are precious—they are intelligent animals that experience complex emotions. Only a small number can be used for human research, and at any rate, they reproduce slowly. They are also more likely to be able to pass on harmful viruses. On the other hand, people already know a lot about how to rear and farm pigs, and their organs are about the right size for humans.

But transferring organs between animals of different species isn’t straightforward. Even organs from another human can be rejected by a recipient’s immune system, and animal tissues have a lot more components that our immune systems will regard as “foreign.” This can cause the organ to be attacked by immune cells. There’s also the possibility of transferring a virus along with the organ, for example. Even if a donor animal isn’t infected, it will have “endogenous retroviruses”—genetic code for ancient viruses that have long since been incorporated into its DNA.

These viruses don’t cause problems for their animal hosts. But there’s a chance they could cause an infection in another species. “There’s a risk that viruses that are endemic to animals evolve in a human and become deadly,” says Chris Gyngell, a bioethicist at Murdoch Children’s Research Institute in Melbourne, Australia.

The team at eGenesis is using CRISPR to address this risk. “You can use CRISPR-Cas9 to inactivate the 50 to 70 copies of retrovirus in the genome,” says Mike Curtis, president and chief executive officer at eGenesis. The edits prevent retroviruses from being able to replicate, he says.

Scientists at the company perform other gene edits, too. Several serve to “knock out” pig genes whose protein products trigger harmful immune responses in humans. And the team members insert seven human genes, which they believe should reduce the likelihood that the organ will be rejected by a human recipient’s immune system. In all, “we’re producing [organ] donors with over 70 edits,” says Curtis.

The team performs these edits on pig fibroblasts—cells that are found in connective tissue. Then they take the DNA-containing nuclei of edited cells and put them into pig egg cells. Once an egg is fertilized with sperm, the resulting embryo is implanted into the uterus of an adult pig. Eventually, cloned piglets are delivered by C-section. “It’s the same technology that was used to clone Dolly back in the ’90s,” says Curtis, referring to the famous sheep that was the first animal cloned from an adult cell.

eGenesis has around 400 cloned pigs housed at a research facility in the Midwest (he is reluctant to reveal the exact location because facilities have been targeted by animal

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By: Jessica Hamzelou
Title: This company plans to transplant pig hearts into babies next year
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Published Date: Mon, 17 Jul 2023 09:13:27 +0000


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