Scientists have edited the pig genome to deactivate a virus that spreads to other cells, an advance that may pave the way for animal-to-human organ transplants.
The shortage of human organs and tissues for transplantation represents one of the most significant unmet medical needs. Pig organs are particularly compatible for transplantation in humans.
The pig genome, however, includes porcine endogenous retroviruses (PERVs), which can be passed on to other cells when cultured together.
Researchers including those from Zhejiang University in China and Harvard Medical School in the US demonstrated the feat in live animals.
The team first confirmed that PERVs in pig cells can be transmitted to human cells when cultured together.
Exposing human cells infected with PERV to uninfected humans cells also resulted in transmission, highlighting the need to deactivate PERVs in pigs if transplantation is to one day occur.
The researchers mapped and characterised the PERVs present in the genome of pig fibroblast cells, identifying 25 in total. They used the gene editing tool CRISPR to deactivate all 25 genomic sites.
Despite the presence of highly modified cells in the population, none of the cloned cells could be grown with greater than 90% PERV editing efficiency.
By adding a concoction of additional factors related to DNA repair, however, the team was able to grow viable cells with 100 per cent of PERVs deactivated.
When they implanted the embryos into sows, they found that the resulting piglets exhibited no signs of PERVs, with some piglets surviving up to four months after birth.
The shortage of human organs and tissues for transplantation represents one of the most significant unmet medical needs. Pig organs are particularly compatible for transplantation in humans.
The pig genome, however, includes porcine endogenous retroviruses (PERVs), which can be passed on to other cells when cultured together.
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Gene editing techniques could prove useful for removing virus genes from the pig genome, paving the way for pig-to-human transplants, yet efforts have so far only been successfully demonstrated in cell lines, not live animals.
Researchers including those from Zhejiang University in China and Harvard Medical School in the US demonstrated the feat in live animals.
The team first confirmed that PERVs in pig cells can be transmitted to human cells when cultured together.
Exposing human cells infected with PERV to uninfected humans cells also resulted in transmission, highlighting the need to deactivate PERVs in pigs if transplantation is to one day occur.
The researchers mapped and characterised the PERVs present in the genome of pig fibroblast cells, identifying 25 in total. They used the gene editing tool CRISPR to deactivate all 25 genomic sites.
Despite the presence of highly modified cells in the population, none of the cloned cells could be grown with greater than 90% PERV editing efficiency.
By adding a concoction of additional factors related to DNA repair, however, the team was able to grow viable cells with 100 per cent of PERVs deactivated.
When they implanted the embryos into sows, they found that the resulting piglets exhibited no signs of PERVs, with some piglets surviving up to four months after birth.