CRISPR Organs? eGenesis Raises $38M For Pig-To-Human Transplants

Xconomy Boston — 

One of the companies trying to revive the once-failed notion of xenotransplantation—transplanting animal organs or tissues into humans—has raised a significant round of cash.

The $38 million Series A round announced by Cambridge, MA-based firm eGenesis comes as the field of human-compatible organs grown in animals, while still years from real products, is back in play because of advances in new biological modification techniques including the genome editing tool CRISPR-Cas9.

Spun out of Harvard University in 2014—one of the firm’s cofounders is Harvard’s George Church, a leading geneticist—eGenesis wants to increase the supply of organs for desperate patients. There are more than 118,000 people on the transplant waiting list in the U.S. alone, and for the most part they must wait for someone healthy to die—a young person in a car accident, for example—to find a match. The number of U.S. transplants rose to more than 33,000 last year but still falls well short of the need.

Soon after its launch, eGenesis made a big splash with a paper in the journal Science that described work from Church and colleagues to make 62 edits in a pig cell to rid it of potentially harmful native pig retroviruses, known by the acronym PERV.

The eradication work was important because the viruses, while harmless to pigs, could pose unknown risks to human hosts.

Since then, eGenesis has also worked on a second goal with CRISPR-Cas9, which works like guided scissors to find a stretch of DNA and snip it out. Cofounder and chief scientific officer Luhan Yang, a coauthor on the Science paper, said that eGenesis, like others working on xenotransplantation, needs to blunt the human immune reaction against foreign tissue, such as a pig lung. To do so, eGenesis has had to use a more advanced function of CRISPR-Cas9—not just knocking out unwanted genes, but swapping in new ones. Call it a genetic repeal-and-replace. (The technical name is homologous recombination.)

Yang said the “immune eradication” part of the work is more complex; the targeted genes can be tens of thousands of base pairs long. Yang would not say which genes or how many eGenesis needs to replace to prevent the human host from rejecting the donated pig organ. “We’re pushing the limits of the technology daily,” she said, and pointed out that one of the challenges is to make a multitude of cuts within a cell without killing it. “We have problems to address,” she said. “This is a work in progress.”

Even with modifications to prevent organ rejection, patients would still need powerful drugs to suppress their immune systems, said Yang.

EGenesis has begun raising pigs from the altered embryonic cells, Yang said, but declined to say if any of them have proven viable—that is, have grown up healthy enough to provide an organ to harvest. She also declined to estimate when a pig-grown organ might be ready for transplant into another kind of animal, let alone into human patients. (The typical animal model for testing pig organ transplants is a baboon.)

She and her colleagues have some catching up to do. A much larger biotech company, United Therapeutics (NASDAQ: UTHR) of Silver Spring, MD, has been planning aggressively for pig xenotransplantation, from research—it has invested at least $100 million in San Diego’s Synthetic Genomics, which is creating the modified pig cells—to new facilities in North Carolina and Florida, to a fleet of drones to rush the harvested organs to hospitals.

Sean Stevens, head of mammalian synthetic biology at Synthetic Genomics, said via email that the partners have produced “hundreds” of viable pigs “with a large variety of genetic modifications.” (In a different application of its modification tools, Synthetic Genomics recently announced it had rewired a salt-marsh bacterium to become a laboratory workhorse to rival E. coli.)

When asked if their lungs have survived when transplanted into other animals, Stevens said that “extraordinary progress of xenolung survival has been made in primate models in a very short time” but did not provide more details.

In a conversation earlier this year, Synthetic Genomics CEO Oliver Fetzer said ultimately the goal is to produce organs that don’t require the recipient to take powerful immune suppression drugs. “But we won’t get there in the first iteration,” he said.

Yang of eGenesis said that the goal of no more immunosuppression is worthy but not if it delays the more practical goal: “We’re trying to address a shortage of organ donors,” she said.

Pig and cow heart valve tissue is used in the repair of human hearts, but organ xenotransplants have been rare. Perhaps the most famous took place in 1984, when a Southern California surgeon gave newborn “Baby Fae” the heart of a baboon. She lived for 21 days but paved the way for human-to-human heart transplants.

The lead investors in the eGenesis Series A round are Biomatics Capital Partners and Arch Venture Partners. Boris Nikolic of Biomatics, which just closed its first fund, and Steve Gillis of Arch have joined the board of directors.

Pig (slightly cropped) by Dan Belanescu via Creative Commons 2.0 license.