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Deadly mushroom poison might now have an antidote — with help from CRISPR

Date:2023-8-14 15:21:55   

Amanita phalloides account for 90 percent of the hundreds of deaths each year from eating poisonous mushrooms. Amanita phalloides, about 15cm tall, with an unassuming tan or yellow-green top, tastes pretty good, according to people who accidentally ate them and survived them. But when eaten, the toxins produced by Amanita phalloides can cause vomiting, seizures, severe liver damage and death. The Roman Emperor Claudius is believed to have died of eating this poisonous mushroom in AD 54, and the Holy Roman Emperor Charles VI also died in 1740, so Amanita phalloides is also known as the "King Killer". Despite their notoriety and history, scientists have long speculated about how deadly Amanita phalloides were. And in medical treatment, for patients who have been poisoned by eating Amanita phalloides, doctors have little recourse to detoxify other than supportive care. Recently, researchers have identified a potential antidote, a chemical called indocyanine green, which blocks the way the mushroom toxin alpha-amanitin enters cells.


Amanita phalloides

Alpha-amanitin is indeed one of the most dangerous compounds in nature. To find an antidote, the researchers first used CRISPR-Cas9 gene-editing technology to create a bank of human cells, each with mutations in different genes. They then screened for which mutations helped the cells survive alpha-amanitin. This CRISPR-Cas9 screen revealed that cells lacking STT3B enzyme function were able to survive the addition of α-amanitin. Interrupting the biochemical pathways involved in STT3B somehow prevented α-amanitin from entering cells. The second step in the researchers' strategy was to screen some 3,200 compounds for one that blocked the function of the STT3B enzyme. Among these compounds, they found indocyanine green, a dye developed by the photography company Kodak in the 1950s and used in medical imaging ever since. After experiments, it was found that only about 50% of mice treated with indocyanine green died of α-amanitin poisoning, while the mortality rate of untreated mice was 90%. The study suggests that gene-editing techniques may finally solve the mystery of how deadly the Amanita phalloides mushroom is, and have found a possible antidote to the deadly mushroom toxin.

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