The article below, from which excerpts are taken, is an excellent illustration of how imprecise and risky CRISPR gene editing is – this time in animals.
The article should be read in full at the link given.
Of course, the CRISPR technology is equally imprecise and risky when applied to plants and it causes exactly the same types of chaos in their genomes, as scientists find when they choose to look. But mostly, plant scientists don't look, and continue to falsely tell the public and regulators that the technology is precise and controllable.
It's often claimed that scientists can weed out the plants where the CRISPR edits didn't do exactly what was wanted. But gene-edited plant developers will only "eyeball" plants to spot those that are clearly defective in that they aren't growing properly or are deformed. They won't check for changes that could make the plant toxic or allergenic – unless forced to do so by regulation. That's why we have to resist attempts to de-regulate gene-edited organisms.
If you're in the UK, take action on the new attempt to de-regulated gene-edited organisms here.
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A Crispr calf is born. It's definitely a boy
Megan Molteni
WIRED, 24 July 2020
https://www.wired.com/story/a-crispr-calf-is-born-its-definitely-a-boy/?utm_source=twitter&utm_medium=social&utm_campaign=onsite-share&utm_brand=wired&utm_social-type=earned
[excerpts only]
* UC Davis scientists spent years editing a sex-determining gene into bovine embryos. In April, Cosmo arrived — and his DNA reveals how far the field has to go
The [CRISPR gene-edited] black calf, while big and strong and healthy, wasn’t exactly what the scientists had hoped to create. A close look at his DNA would expose just how unpredictable Crispr gene editing can be and how much more scientists still need to learn before the technology can become routine practice for animal reproduction....
Crispr had made the cuts it was supposed to. But then it made some more. So in the location where Van Eenen[n]aam and Owen had intended to paste a single copy each of SRY and GFP, it got much messier. On one arm of chromosome 17, the new DNA didn’t take at all. The cell randomly grabbed 26 DNA letters to fill the gap. (That’s pretty normal for how cells repair double-stranded DNA breaks). It was the other arm where the real action happened. In about 90 percent of cells, seven copies of SRY and GFP had been plopped in. Two of them had been inserted backwards. And the bacterial plasmid was in there, too. In about 10 percent of cells, there were three (properly oriented) copies of the SRY-GFP construct and one plasmid....
Other experiments abroad, aimed at bringing designer farm animals to market, have turned up strange side effects in recent years, including enlarged tongues in rabbits, pigs with extra vertebrae, and premature deaths of cattle. Lisa Moses, an animal bioethicist at Harvard Medical School, told the Wall Street Journal at the time of such reports that “It’s really hubris of us to assume that we know what we’re doing and that we can predict what kinds of bad things can happen.” ...
The UC Davis team made their initial analyses of [gene-edited bull] Cosmo’s genome public on Thursday morning, at a poster presentation of the American Society of Animal Science. Gaétan Burgio, a geneticist at the Australian National University in Canberra who reviewed the results, says he is not surprised by the less-than-perfect outcome. His group routinely uses Crispr to add new genes to mouse DNA to make new models for studying human diseases. Multiple copies and unwanted plasmid insertions are very typical, he says. “We’ve seen plenty of this in mice,” he says. Sometimes cells will incorporate multiple copies of the bacterial DNA. Burgio has seen up to 70 in one animal. “It’s an absolute nightmare to do knock-ins using Crispr,” he says.
The chaos all comes down to the kinetics of the gene editing enzymes, he says. Any time you break the DNA cleanly in two, it’s hard to control the outcome. But scientists didn’t really know that in the early years of Crispr gene editing research, when Van Eenennaam started her all-male cattle project. Reports of erroneous insertions and other undesirable alterations didn’t start showing up in mice until around late 2017, says Burgio.
Some newer Crispr constructs avoid such mistakes by only nicking the DNA, limiting the opportunities for unwanted insertions. But these systems are often fickle in other ways—they might only work in a small fraction of cells or make other kinds of off-script edits. “The bottom line is: There’s no perfect tool,” says Burgio. The design and analysis of the UC Davis team’s cattle experiment look sound to him. Yet it’s further proof that using Crispr to redesign livestock DNA is still a very new science. “Right now we are good at making gene editing in animals efficient, but we are not yet good at making it safe. I think we’ll get there. But we have a fair bit of work still left to do,” he says.
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