Whoopsies —

Gene-edited cow project on the butcher block after bacterial genes found.

A Holstein calf, which has not been gene-edited.

A Holstein calf, which has not been gene-edited.

A Minnesota-based gene-editing company is left red in the face after it took on bull genetics—and got slammed.

The company, Recombinetics, set out years ago to genetically engineer Holstein dairy cattle to come without their troublesome horns, which farmers typically remove to keep themselves and other cows safe. In 2015, the company seemed to have succeeded, unveiling two hornless bulls, Spotigy and Buri. Recombinetics touted them as a bona fide, 100%-bovine success story.

Though Spotigy was sacrificed for research,Buri lived on to sire 17 offspring—one of whomgraced the cover of Wired, as MIT Technology Review notes. And, until just a few months ago, Brazil was set to createa herd of hornless Holsteinsfrom shipments of Buri’s sperm, Wired reported.

But the plans were bucked after scientists at the Food and Drug Administrationstumbled uponan utterly damning findearlier this year—Buri isn’t all bull: he’s a wee bit bacterium.

Bullish edits

When Recombinetics edited the cow cells that would later give rise to Buri, the company did so using bacterial DNA-editing machinery—which inadvertently got stitched into Buri’s genome.

The machinery involved are called TALENs (transcription activator-like effector nucleases), which are enzymes that can be customized to snip a targeted spot in a genetic code. That break in the code can then be patched up with a desired DNA sequence—say, a stretch of DNA that leads to hornlessness, swiped from other, hornless cattle breeds.

Recombinetics’ scientists used a standard method to get the TALENs into the cow cells—they delivered the TALENs via a loop of bacterial DNA called a plasmid. Usually, after the plasmid-encoded TALENs do their snipping, the plasmid’s work is done and it doesn’t hang around. But in Buri’s case, the whole plasmid ended up inserting itself into the bull’s genome, right next to the inserted stretch of DNA for hornlessness.

That means that Buri’s genome contains the entire DNA sequence of the plasmid. And in addition to all the bacterial-editing machinery from the loop of DNA, Buri’s genome includes the antibiotic resistance genes present on the plasmid, too—though they’re unlikely to have any effect.

Blind spot

The plasmid insertion is a big cow plop. But the fact that the company didn’t find the problem itself is perhaps more embarrassing.

“It was not something expected, and we didn’t look for it,” Tad Sonstegard, CEO of Acceligen, a subsidiary of Recombinetics that owns the animals, told MIT Technology Review. He added that a more thorough check “should have been done.”

The FDA scientists who found the problem agreed.In their reporton the case, they noted that their find “highlights a potential blind spot in standard genome-editing screening methods.”

However embarrassing, the genetic insertion is unlikely to affect the cows or anyone who might end up eating them. As Sonstegard put it, they’re “safe to eat with or without the plasmid.”


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