The shortage of human organs and tissues for transplantation represents one of the most significant unmet medical needs.
While pig organs are best compatible for organ transplantation in humans, their genome, however, includes porcine endogenous retroviruses (PERVs), which can be passed on to other cells when cultured together.
In the study, published in the journal Science, the researchers removed the virus genes from the pig genome using CRISPR-Cas 9 — a gene editing tool — in live animals.
The experiments were so far only successfully demonstrated in cell lines, not live animals.
“Using CRISPR-Cas9, we inactivated all the PERVs in a porcine primary cell line and generated PERV-inactivated pigs via somatic cell nuclear transfer,” said one of the researcher Luhan Yang, from the Harvard Unversity.
“Our study highlighted the value of PERV inactivation to prevent cross-species viral transmission and demonstrated the successful production of PERV-inactivated animals to address the safety concern in clinical xenotransplantation,” added Yang, who is also the co-founder of eGenesis — a US-based life sciences company — involved in the study.
Xenotransplantation is the process of grafting or transplanting organs or tissues between members of different species.
For the study, the researchers identified 25 genomic sites where PERVs present in the genome of pig fibroblast cells, and using CRISPR they deactivated all.
Despite the presence of highly modified cells in the population, none of the cloned cells could be grown with greater than 90 per cent 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, the piglets exhibited no signs of PERVs, with some piglets surviving up to four months after birth, the researchers said