Modified pig organs may be possible for use in humans, but not as quickly as researchers hoped
Tuesday, June 25, 2019
Despite estimates that gene-edited pig organs would be available for use in humans by this year, research continues on the plan that could alleviate critical organ shortages.
In 2017, founders of the startup eGenesis announced plans to use CRISPR gene-editing technology to make pig organs safe for use in humans. At the time, eGenesis co-founder and Harvard geneticist George Church predicted that modified pig organs would be available for use in humans within a year, maybe two. However, Church admits his prediction hasn't come to fruition.
To date, xenotransplantation, or animal-to-human transplants, has only been used in monkeys to varying degrees of success.
“What we’re doing is a necessary step,” said Dr. James Markmann, the chief of transplant surgery at Massachusetts General Hospital in Boston, where the research is underway by eGenesis. “We’d be hard-pressed to put a modified organ into a human until it’s been tested in a large animal.” Markmann is an advisor to eGenesis.
Researchers haven't divulged what type of primates or which types of organs are being studied in the experiments but say the organs are highly engineered. Before the modified organs can be used in a human recipient, there are obstacles to overcome.
First, eGenesis's results and those of the other companies working on xenotransplantation haven't been consistent. Some baboons live for several months after transplantation while other animals die very quickly.
“We feel there is some biological reason for that,” said Luhan Yang, eGenesis's co-founder and chief scientist. “We are investigating and trying to fix that.”
Plus, governmental regulators haven't indicated under what circumstances they would allow clinical trials using human subjects. At this point, even the pigs that contain the organs are heavily regulated. eGenesis and a partner company in China have produced hundreds of pigs with various genetic modifications, but the pigs or their organs cannot be transported between the two countries.
Finally, there's debate over how much the organs' gene need to be modified before transplanting to a human candidate. The company has touted the ability to perform 62 simultaneous gene modifications that deactivate viruses found naturally in the porcine genome. More recently, eGeneis says it is using a “double digit” number of gene additions and deletions to make porcine organs less likely to trigger immune rejection in the recipient animal.
Muhammad Mohiuddin, director of the program in cardiac xenotransplantation at the University of Maryland School of Medicine, says removing the viral genes could cause unintended effects, thus harming the animals.
Rather, eight or nine gene edits can yield a pig with multiple usable organs, he said. That way, scientists don't have to create one pig for heart transplants, another for kidneys and so on. “Otherwise the organs go to waste,” he said.
Even with the challenges, Markmann remains optimistic about using gene-edited pig organs in humans. “The fact that there are pig organs surviving for six months or a year, or a couple of years, is really extraordinary, and it says this can be done,” he said. “Everybody sees that we’re at a turning point.”
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