Thanks to a powerful new gene-editing technique, researchers have made a stride toward engineering safer pig organs for human transplants. In a paper in Science today, they describe using the CRISPR editing method in pig cells to destroy potentially harmful DNA sequences at 62 sites in the animal’s genome. It’s the most extreme example to date of the precise yet widespread genetic changes possible through CRISPR. It’s also raising hopes that the technology can finally render pig organs fit for human bodies—a goal that some of the paper’s authors are already pushing further with a private company.

About 122,500 people in the United States alone are waiting for a life-saving organ transplant, and some have argued that a steady supply of pig organs could make up the shortage, because they are similar in size to those of people. But so far, no one has been able to get around the violent immune response that pig cells provoke. And these cells pose another, longer term potential risk: Their DNA is riddled with many copies of a DNA sequence that is the remnant of a virus and can still produce infectious viral particles. This porcine endogenous retrovirus (PERV) has been shown to move from pig to human cells in a dish, and to infect human cells transplanted into mice with weak immune systems.

These shadowy PERV sequences are the target of the new CRISPR experiment, from geneticist George Church of Harvard University and colleagues. Church believes the new work could revive the idea of xenotransplantation, as the use of animal organs in people is called. “Basically, this whole field has been in the doldrums for 15 years,” he says. “There’s been kind of a few true believers that had it on life support. But I think this changes the game completely.”

With CRISPR, a method based on the ancient defense mechanism that bacteria use to demolish the DNA of invading viruses, researchers can target a specific point in a genome with a short strand of guide RNA and then slice it with an enzyme to precisely disrupt a gene or insert a new one. Church’s team designed guide RNA that targets a gene common to all 62 of the PERV sequences in the DNA of pig kidney cells. In a small subset of these cells, the CRISPR system obliterated every instance of the targeted gene—by far greatest the number of gene changes so far achieved with a single round of CRISPR. And those edited cells showed up to a 1000-fold reduction in their ability to infect human kidney cells with PERV in a lab dish.

That cells even survived having their DNA hacked up in 62 places is remarkable, says molecular biologist Jennifer Doudna of the University of California, Berkeley, one of the original developers of CRISPR. The same approach could be useful as a research tool to probe the function of many repetitive sequences nestled in the human genome, some of which appear to be activated during viral infections, she says. “Maybe this will encourage labs to say ‘Hey, let’s make a bolder change in one shot.’” Other groups have managed to modify up to six sites, and up to five different genes, at a time.

Church cautions that editing many instances of a single, repetitive gene sequence isn’t the same as targeting many unique genes at once—which will be necessary if CRISPR is to become a treatment for complex genetic diseases, for example. He suspects the experiment worked because it took advantage of an apparently rare phenomenon called gene conversion in which DNA sites already inactivated by CRISPR helped stop other recently cut sites from being correctly repaired by the cell, leading to a snowball effect that resulted in all the PERV copies ending up deactivated for good. “We’re not convinced that what we did is generalizable,” he says. “It doesn’t mean that we can now change 62 different genes easily.”

But the result has immediate relevance for developing transplantable pig organs. At a National Academy of Sciences meeting on genome editing last week, Church, who co-founded a company called eGenesis for that purpose, reportedly said that his group has successfully created pig embryos with inactivated PERV sequences—the next step toward raising cloned pigs with retrovirus-free organs. That feat isn’t reported in the Science paper. Church says his group has successfully inactivated PERVs in cells from living pigs, and transferred the nuclei of those cells into pig embryos, but wouldn’t confirm that the PERVs were inactivated in the embryos. “We are not ready to discuss the embryo experiment beyond saying that we have done them,” he says.

If PERV risks can be taken off the table, cross-species transplantation researchers will have “one less issue to deal with,” says Daniel Salomon, a transplant immunologist and physician at Scripps Research Institute in San Diego, California. But to make transplant-ready pigs, researchers also have to identify the many other molecules in pig cells that cause the human immune system to reject them, and knock the gene for each out in a way that doesn’t kill the pig. Church says his team has such a list, and is working on disabling each of them with CRISPR and other methods. They hope to have immune-friendly, PERV-free embryos ready to implant in surrogate mother pigs in 2016.

Church’s success isn’t necessarily good news, says one veteran xenotransplantation researcher. David Cooper, a transplant immunologist whose group at the University of Pittsburgh Medical Center in Pennsylvania is also exploring pig organ transplants, notes that regulatory agencies such as the U.S. Food and Drug Administration (FDA) have already indicated that the presence of PERVs wouldn’t necessarily hold up a clinical trial. In fact, he worries that the newfound ability to remove PERV elements could slow progress in the field as regulators “may now request we do this (without any evidence that it is necessary).”

Salomon, who headed an FDA advisory panel on the risks of cross-species transplants, disagrees. “I’m not freaked out about PERV anymore,” he says, but “if you can reduce by 1000-fold the potential of PERV transmission, you should do it.” He also sees an oncoming resurgence in the field as researchers consider ways to edit away all the other features that cause organ rejection. “This first paper on the PERVs shows that that’s not so crazy.”