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In this picture taken on June 5, 2017 a piglet is seen at a pig farm on the outskirts of Beijing.  NICOLAS ASFOURI AFP/Getty Images
Commentary

One Day You Might Have a Pig Organ. And It Could Save Your Life.

Aug 16, 2017

Organ transplants save the lives of people whose own body parts fail, yet the supply of human donor organs will never be enough to keep every one of the 116,000 patients in the United States on the transplant waiting list alive. The need for more options has never been greater. But now, we have encouraging scientific evidence that new organ transplant sources may finally be within closer reach.

In the August 10 issue of Science, we report on one of the most promising developments in the quest for safe new organ and tissue sources. For more than 100 years, humans have considered the potential for pigs to generate donor organs because they share much of the same anatomy. However, the risk of a virus endemic to pigs has stymied xenotransplantation efforts—until now.

The virus, known as Active Porcine Endogenous Retrovirus, or PERV, is a type of retrovirus found in pig DNA. Although not always active, the risk of cross-species disease transmission has precluded the use of pig organs for human transplant.

Now, our team at eGenesis has successfully manipulated the pig embryo genome to eradicate PERV. Those modified embryos were then implanted into sows, resulting in the first-ever pigs born free of the virus. Further study of these piglets will verify the long-term results, but so far, there is no evidence of PERV in the genetic material of the new line of piglets.

This is a remarkable achievement made possible by the enormous advances in genetic engineering and our ability to understand cells and the DNA that directs how those cells function and replicate. Other barriers remain, such as organ rejection sparked by the human immune response, but these PERV-free pigs are an important step toward addressing safety concerns about cross-species virus transmission.

Our process is based on the genome-editing tool CRISPR, which refers to Clustered Regularly Interspaced Short Palindromic Repeats occurring in the genome of certain bacteria. It can selectively delete, modify, or correct a disease-causing abnormality in a specific DNA segment. CRISPR technology uses a protein-RNA complex composed of Cas-9, which binds to a guide RNA (gRNA) molecule that has been designed to recognize a particular DNA sequence.

CRISPR and next-generation genome-editing tools may also help us address other outstanding issues of using pig organs for human transplantation. Our hope is to edit the pig genome to create immune and functional compatibly between pig organs and human recipients.

There are many questions that need to be addressed before xenotransplantation becomes a clinical reality. The risk of cross-species transmission of virus has been a good reason to proceed with caution. Our scientists at eGenesis have been working toward a safe, responsible, and near-term pathway to human clinical testing, though it is too early to speculate on timelines. We have taken lessons from previous clinical experience and combined it with the latest innovations in both research and technology to power our groundbreaking platform. The potential to deliver safe and effective transplantable cells, tissues, and organs for humans around the world represents a powerful opportunity to address a dire need.

More than 20,000 people in the United States have received donor organs so far this year, but tens of thousands wait anxiously every day. Every 10 minutes, another person joins the waiting list, and every day, 20 people die because no organ was available to them. We strive to create a world where there is no organ shortage. That is the best way to honor all life and have a major impact on public health worldwide.

Luhan Yang, Ph.D. is chief scientific officer and co-founder of eGenesis.

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