Rewriting Life

CRISPR May Speed Pig-to-Human Transplants

Startup says it will edit pigs’ genes to prepare organs for harvest.

“This pig might save your bacon.”

So say the company T-shirts printed up by biotechnology startup eGenesis, which today raised $38 million to fund a new effort to edit the DNA of pigs so they can serve as the source of transplant organs.

The plan, says the company, is to use the gene-editing method known as CRISPR to introduce extensive DNA modifications into pigs as a way of humanizing their organs so they won’t get rejected if transferred into a person. (The back of the T-shirt reads: “PS, I like my bacon extra CRISPR’ed.”)

The company is a spinout of the lab of Harvard Medical School geneticist George Church. He and cofounder Luhan Yang, who is also chief scientific officer, showed in 2015 that using gene editing, a novel and powerful way of modifying DNA inside living cells, they could eliminate viruses that lie latent in the pig’s genome.

Now the group plans even more extensive modifications to pigs, including using gene editing to snip away pig molecules that the human body attacks. Yang says the company will also add to the pig’s genome genes that modulate the immune response and modify certain factors involved in coagulation.

The idea of xenotransplantation—or using animal organs to replace human ones—fell out of favor in the 1990s because of evidence that pig or baboon organs unleashed severe immune storms and would be swiftly destroyed in the human body. Regulators also worried about the risk of spreading infectious disease between species.

Progress since then has been fairly slow. Revivicor, a division of the biotechnology company United Therapeutics that is based in Blacksburg, Virginia, has used more conventional genetic engineering to produce GM pigs. In 2015, a pig heart that it made succeeded in surviving inside a baboon for 945 days, still a record.

The need for organs remains acute. Everyone eventually dies of organ failure. But there are millions whose lives could be extended if only they could get a replacement heart, liver, kidney, or lungs. The problem is even worse in China, says Yang, since organ donation is not widely accepted there.

Currently, eGenesis is working only with pig cells in the lab. It is developing two different designs. One is for a pig with a “humanized” immune system and the other is for a pig cleansed of risky viruses. Eventually, both sets of genetic changes will be merged into a single pig cell.

After that, says Yang, the cell will be turned into a pig using cloning. The cell will be injected into an egg to form an embryo and then transferred to a surrogate sow. 

The approach avoids some concerns around CRISPR, including the possibility that it can introduce unwanted, accidental edits to DNA. The pig cells can be scrutinized for any genetic errors while still in a lab dish. eGenesis may also learn just how extensively pigs can be modified before they start developing health problems of their own.

“What’s the combination of immune modifications that get to a viable organ and a viable pig? That’s what we’re focused on this year,” says Julie Sunderland, managing director of Biomatics Capital, which along with ARCH Venture Partners is among the xenotransplant company’s new investors.

Sunderland says that successfully editing pigs is just one challenge ahead. Before any person receives a CRISPR-ized pig organ there will be years of negotiations with regulators, close work with transplant surgeons, and costly experiments putting pig organs in monkeys. “Everybody tends to focus on the gene editing because it is so sexy, but it is a multifaceted challenge that we’ll need to tackle over the next few years,” she says.

Muhammad Mohiuddin, chief of the transplantation section at the National Heart, Lung, and Blood Institute and the National Institutes of Health, says he’s pleased xenotransplantation is attracting new commercial investment. Just one transplant experiment using large animals, like putting a pig heart in a monkey, costs $100,000, he says.

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