The cells that survive provide clues as to which genes interact with the toxin.
Neely and her team used CRISPR detection in 2019 to develop a potential treatment for the excruciating and often fatal sting of a box jellyfish.
The screening revealed that the box jellyfish’s venom needs the body’s cholesterol to function. Neely’s team used this knowledge to develop an antidote from existing cholesterol-lowering drugs, which blocked the venom’s ability to kill cells, inflict pain, and cause tissue death and scarring.
Similarly, the study of the death cap, published in nature communications, analyzed the role of more than 19,000 genes and identified an enzyme called STT3B that is key to amanitin toxicity in the body.
The ICG dye binds to STT3B, which blocked the enzyme’s activity and halted the toxic effect of the kill plug in laboratory-grown liver cells and in mice when administered within four hours of poisoning.
Neely said the disclosure has the potential to save many lives.
“I think this is a really awesome application of CRISPR detection. My feeling was that it would be quite difficult to find an antidote for such a potent toxin,” she said.
“The next step would be to test in humans, and this type of test will be difficult to establish due to the rarity of this type of poisoning. I think China could be the perfect country to be able to manage human trials of this antidote, so I’m looking forward to seeing what happens next.”
There were 40,000 mushroom poisonings and 788 reported deaths in China between 2010 and 2020. Death caps closely resemble straw mushroom, a species commonly cooked in Asian kitchens.
At least six people have died of poisoning in Australia, including two Canberrans who ate the toxic mushroom at a New Year’s Eve dinner in 2012. The mushrooms sprout in autumn and early winter after rain and grow in symbiosis with oak trees, the most commonly in Canberra, Melbourne and Adelaide.
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