A genetic-engineering tool designed to spread through a population like wildfire — eradicating disease and even whole invasive species — might be more easily thwarted than thought.
Resistance to the tools, called CRISPR gene drives, arose at high rates in experiments with Drosophila melanogaster fruit flies, researchers at Cornell University report…in PLOS Genetics.
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Gene drives are basically genetic copy-and-paste machines. These self-perpetuating machines are inherited by more than 50 percent of offspring of an individual carrying a gene drive. Working perfectly, they could transmit to 100 percent of offspring.
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If everything works correctly, cells repair [the affected chromosome] by copying the gene drive onto the cut chromosome. But the slice can also be fixed by gluing the cut ends back together. That regluing sometimes leads to mistakes that destroy Cas9’s cutting site, creating a chromosome that is resistant to the gene drive’s insertion.
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Some people might think that high rates of resistance mean that gene drives are safe to release because they won’t spread easily in the wild. But that notion is misguided, says Bier. Even if a gene drive is able to affect only a small percentage of a local pest population, it could still spread around the world, Esvelt adds. “It could still screw us all over in the current form.”
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