Scientists on Thursday announced a breakthrough in producing the first batch of live pigs free of dangerous viruses, setting the stage for transplanting life-saving organs from the animals into humans.
In a paper published in the U.S. journal Science, researchers from the U.S., China and Denmark described how they used the powerful gene-editing tool CRISPR to modify pig cells and produce embryos free of the so-called porcine endogenous retroviruses (PERVs) in order to create the desired piglets.
Luhan Yang, co-founder and chief scientific officer at a Massachusetts-based biotechnology company called eGenesis, who led the study, hailed the first PERV-free pigs as “an important milestone” for the use of animal organs for human transplant.
“Our work fundamentally addressed the risk of cross-species viral transmission in xenotransplantation,” Yang told Xinhua.
Worldwide, human organs for transplant are in short supply. Researchers and clinicians have long hoped that the challenge could be alleviated through the availability of suitable animal organs for transplant, a concept known as xenotransplantation.
Pigs in particular have been especially promising candidates due to their similar size and physiology to humans. But one of the largest safety concerns has been the fact that most mammals including pigs contain repetitive, latent retrovirus fragments in their genomes — present in all their living cells — that are harmless to their native hosts but can cause disease in other species.
The presence of PERVs in pigs brought more than a billion dollars’ worth of pharmaceutical industry investments in developing xenotransplant methods to a standstill by the early 2000s, according to the study.
Then, Yang and colleagues demonstrated in a 2015 Science paper a method to inactivate all 62 copies of PERVs in porcine cells and eliminated PERV transmission to human cells.
In the new study, the researchers developed a strategy to enable efficient and precise gene editing to deactivate all 25 genomic sites related to PERVs in pig fibroblast cells using the CRISPR technology.
In conjunction with a method to inhibit cell death during gene editing, they successfully produced viable PERV-free porcine embryos via somatic cell nuclear transfer, the same method that created Dolly, the world’s first cloned sheep, in 1996.
The team then implanted the PERV-free embryos into surrogate sows and demonstrated the absence of PERV re-infection, initially in fetuses and finally in recently born piglets.
“At least for those who are four months old, we did not observe difference in physiology between the modified piglets and normal ones,” Yang said.
“We will continue to use this platform to engineer the pig genome, on the basis of PERV-free pigs, to enhance pig-to-human immunological compatibility for the clinical xenotransplantation of porcine organs as early as possible,” she said.
The paper was also authored by researchers from Harvard University and China’s Zhejiang University, Yunnan Agricultural University, Third Military Medical University and Research Institute of Shenzhen Jinxinnong Technology Co Ltd as well as Denmark’s Aarhus University.
Professor Darren Griffin of the University of Kent, who was not involved in the study, said the finding represents “a significant step forward towards the possibility of making xenotransplantation a reality.”
“However, there are so many variables including ethical issues to resolve before xenotransplantation can take place,” Griffin cautioned.
Another outside expert, Professor Ian McConnell of the University of Cambridge, sounded a similarly cautionary note, calling this work “a promising first step.”
“It remains to be seen whether these results can be translated into a fully safe strategy in organ transplantation,” McConnell said.
“Even if organs from these gene-edited pigs could be safely used to overcome virus transmission, there remain formidable obstacles in overcoming immunological rejection and physiological incompatibility of pig organs in humans.” Enditem