Deal Aims to Grow “Humanized” Organs in Pigs for Transplantation

5/6/14Follow @bvbigelow

A San Diego startup that specializes in re-engineering genes and a multi-billion-dollar biotech giant in Silver Springs, MD, say they are now working together on an audacious goal—developing “humanized” organs in pigs that can be transplanted into humans.

Under a multi-year R&D collaboration being announced today, San Diego-based Synthetic Genomics and Lung Biotechnology, a subsidiary of United Therapeutics (NASDAQ: UTHR), intend to eliminate the genomic incompatibilities that lead to rejection in lung transplants. The United Therapeutics subsidiary agreed to make a $50 million investment in Synthetic Genomics as part of the deal.

The ambitious effort is the latest example of the unfurling potential in genomic medicine—and also the latest quest put forward by J. Craig Venter, the pioneer in human genome sequencing who co-founded Synthetic Genomics in 2005 with the Nobel laureate Hamilton Smith. Just two months ago, Venter announced that he was starting a new company to sequence the entire genomes of thousands of people in a bid to identify and repair the genetic causes of age-related diseases like cancer and heart disease.

The problem with human lung transplantation, Venter said by telephone yesterday, is there are nowhere near enough human organs available to meet the need. “We need a ready source [of donor lungs], and the genetic tools are now available,” he said.

Even with the tools, though, the challenge is both enormous and complex. Venter says the concept of developing humanized lungs calls for modifying a substantial number of genes in pig cells. According to a joint statement from the two companies, United Therapeutics would then use its expertise in xenotransplantation “to implant these engineered cells, generating pig embryos which develop and are born with humanized lungs.”

This phrasing is a little vague, and I should have asked Venter how, exactly, this would be done. As I understand it, the process would modify the genes of a pig zygote—the cell formed after initial fertilization—so the lungs of a pig embryo (or many pig embryos) would develop “humanized” lungs designed specifically to minimize their genetic incompatibilities with human hosts.  These pig embryos would be implanted in sows and birthed. The piglets would continue to grow to maturity, or until their genetically modified lungs could be transplanted into a human patient with end-stage lung disease.

Pig organs are anatomically about the same size as human organs, and the methods needed to raise pigs in sufficient numbers are already well-understood, Venter said.

Still, it would be a “huge leap,” Venter explained. The DNA synthesis, genome editing, and genome modification technology that would be required has been perfected for humanized monoclonal antibodies—individual immune cells. But nobody has been able to rewrite so much of the genetic code, or even attempted to, he said.

More than 400,000 people die each year in the United States from various types of lung disease, including cancer, Venter said. Only about 2,000 lung transplants are done annually, according to the Registry of the International Society for Heart and Lung Transplantation, due primarily to a donor lung shortage.

In the statement today, the companies say, “Not even 1 percent of deaths due to lung failure can be avoided due to the gross shortage of transplantable human lungs. Previous attempts to rectify this shortage with animal organs have failed due to genomic incompatibilities, especially with respect to immune and coagulation systems. The collaboration between Synthetic Genomics and Lung Biotechnology aims to eliminate these genomic incompatibilities.”

United Therapeutics, founded in 1996, generates all of its revenue from drugs and related products used in cardiopulmonary medicine, which amounted to over $289 million in the quarter that ended March 31. Yet the company also says on its website, “While building business value in the cardiopulmonary medicine field, we are also laying important foundations for future franchises in lung transplantation.”

Venter said he met United Therapeutics CEO Martine Rothblatt several years ago, and described himself as “a long-term fan of what they’ve been doing.” He added that discussions leading to their collaborative agreement began early this year.

Bruce V. Bigelow is the editor of Xconomy San Diego. You can e-mail him at bbigelow@xconomy.com or call (619) 669-8788 Follow @bvbigelow

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