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Wyss Scientists Excise Retroviruses From Pig Genome, Eye Transplantable Organs for Humans

NEW YORK (GenomeWeb) – Scientists in George Church's laboratory at Harvard Medical School and the Wyss Institute for Biologically Inspired Engineering have reported successfully removing endogenous retroviruses from porcine kidney epithelial cells.

In a study published today in Science, the scientists — led by first authors Luhan Yang, Marc Güell, Dong Niu, and Haydy George —achieved multiplexed CRISPR/Cas9 genome editing in a PK15 cell line, eliminating all 62 copies of porcine endogenous retroviruses (PERVs) simultaneously and vastly reducing the transmission to human cells.

To edit the PERVs, they targeted the highly conserved catalytic center of the pol gene, a crucial reverse transcriptase. Transient transfection was not efficient, so the authors turned to a PiggyBac transposon system to deliver a doxycyline-inducible editing system.  The previous record for simultaneous multiplexing of CRISPR/Cas9 editing was six targets, the authors said, though the new study technically targeted one gene 62 times, using two guide RNAs.

The study could point the way towards transplanting pig organs into humans, a process called xenotransplantation, which would address the gap between patients in need of organ donations and the number of available organs. "Pig kidneys can already function experimentally for months in baboons, but concern about the potential risks of PERVs has posed a problem for the field of xenotransplantation for many years," David Sachs, an emeritus professor at Harvard Medical School who was not an author of the study, said in a statement.

"The lack of ability to remove [PERVs] from pig DNA was a real showstopper," Church added, noting that the concerns had bogged down the field of xenotransplantation since the early 2000s.

Sachs said that if Church's lab could do the same kind of editing in pig embryos and grow the pigs to maturity, "they would eliminate an important safety concern facing this field."

Church, Yang, and Güell are co-founders of eGenesis, a firm looking to advance xenotransplantation to the clinic. The firm faces competition in that space, with Lung Biotechnology making a recent fundraising splash.

Last month, Synthetic Genomics invested an additional $50 million in Lung Biotechnology, expanding on an initial investment of $50 million and a collaboration to grow pig organs for transplantation.