NOV 21, 2015 6:39 AM PST

CRISPR/Cas9 Gene Editing in Pigs to Solve Organ Shortage?

WRITTEN BY: Xuan Pham
The United Network for Organ Sharing (UNOS) tabulated that 122,563 people currently are in need of a lifesaving organ transplant. They estimate that on average, 22 people die each day while waiting for a transplant didn’t happen, because of a shortage in human organ donations. But what if we look elsewhere for organs to transplant?
 
Could the Pigs be Our Dependable Organ Source?

As it turns out, scientists have looked to other animals as potential organ donors, but every small milestone has been blemished by larger setbacks related to organ rejection. But transplantation medicine has been revived again by a new era of gene-editing techniques called CRISPR/Cas9. Will this technology enable scientists to overcome the barriers of cross-species transplantation and fill the need for organs?

Pigs are, surprisingly enough, considered the next best candidate for providing organs for human transplants. The organs of the pig are exposed to a similar immune system as humans, and also shares similar functions and a close size match to ours. Already pigs have been of great service to medicine, as doctors have been replacing damaged human heart valves with pig valves for the past 50 years.

But moving from organ part to whole organ has been especially challenging. So far, lab trials of transplanted pig organs into baboons have been discouraging, with successes measured in days. Failure of the transplant to sustain in another animal is largely due to the host’s tendency to recognize and attack foreign organs. In addition to immunosuppressant drugs, scientists have found a few ways to block a pig antigen called α-1,3-galactose that seems to trigger most of the immune responses. They’ve created a pig that’s entirely missing the α-gal, removing the antigen completely. But despite these advances, the immune system has turned out to be much more complex than they anticipated. The current record for a pig-to-baboon kidney xenotransplantation is 136 days.

Enter the CRISPR/Cas9, a gene editing technology that’s taken the science community by storm. The system is heralded as a game-changer for many areas of science, but it may be the biggest game-changer for transplantation medicine. Because of its efficiency and specificity at editing genes, researchers can now quickly and accurately silence genes in the pig that could cause rejection or infection in the human.

CRISPR/Cas9 can do this and much more: it has allowed scientists to target multiple genes all at once. In other words, systematic silencing of all the antigen genes in the pigs would take decades, whereas CRISPR/Cas9 would reduce this time to mere months. Already a life-sciences company eGenesis, announced that it had edited the pig genome in 62 places in one go with one molecule. The 62 genes corresponded to viral genes in the pigs, PERVs, which once edited, could no longer trigger viral infections. eGenesis is coincidentally headed by George Church, one of the seminal experimentalists who optimized the CRISPR/Cas9 technology.

“This work brings us closer to a realization of a limitless supply of safe, dependable pig organs for transplant,” Dr. David Dunn, transplantation expert at the State University of New York at Oswego.

The announcement of this CRISPR/Cas9 application renewed much hope and eagerness for pig-to-human organ transplantation. Because it’s so accurate, fast, and easy, many researchers can conceive editing more pig immune genes in one fell swoop. For every immune gene that’s silenced, the odds of the transplanted organ being rejected should go down, and we should be one step closer to a dependable organ source. Though for the many people on the organ wait list, CRISPR/Cas9 could not act fast enough.
 

Source: Nature 
 
About the Author
  • I am a human geneticist, passionate about telling stories to make science more engaging and approachable. Find more of my writing at the Hopkins BioMedical Odyssey blog and at TheGeneTwist.com.
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