[Reading Science] Found Antidote for Deadly Poisonous Mushroom Using Gene Scissors

Chinese Sun Yat-sen University Research Team
Reveals Detoxification Effect of 'Indocyanine Green'

Amanita phalloides, known as the "mushroom among poisonous mushrooms," is infamous for its deadly toxicity. Many kings have died after consuming this mushroom, earning it the nickname "killer of kings." Recently, scientists have attracted attention by developing an antidote to the mushroom's lethal toxin using advanced gene-editing technology.

White-spotted Puffball Mushroom

On the 16th (local time), a research team from Sun Yat-sen University in Guangzhou, China, published a paper on this topic in the international journal Nature Communications. This mushroom, which can grow up to 15 cm, has a pale yellow-brown or yellow-green color. According to some survivors who were lucky enough to live after ingestion, it also tastes very good. However, the toxin contained in this mushroom, called amanitin, can cause vomiting, seizures, severe liver damage, and even death. It is believed that Roman Emperor Claudius and Charles VI of the Holy Roman Empire died after consuming this poisonous mushroom. Even today, hundreds of people die annually from toxic mushroom poisoning, with 90% of these cases attributed to this mushroom.

Despite its deadly reputation, scientists had not yet precisely identified the mechanism by which this mushroom exerts its toxicity. Treatment for patients who accidentally ingested it was limited to inducing vomiting and managing symptoms, as no antidote was available unlike for other poisons.

However, the Sun Yat-sen University research team recently discovered that a substance called indocyanine green can be used as an antidote. It works by blocking the biological pathway through which the mushroom’s toxin, α-amanitin, acts on cells. This discovery was made by applying a method previously used to find an antidote for jellyfish venom. The team first used the latest gene-editing technology, CRISPR-Cas9, to create human cell lines with different gene mutations. They then exposed these cells to α-amanitin to observe which mutated cells survived. The results showed that human cells deficient in an enzyme called STT3B survived despite exposure to α-amanitin. STT3B is responsible for adding sugar molecules to proteins, and by inhibiting this enzyme, α-amanitin’s entry into cells is blocked, preventing the toxin from causing fatal symptoms in the body.

The research team then screened 3,200 chemical compounds to find one that could inhibit STT3B activity, ultimately selecting indocyanine green. This substance is a type of dye originally developed in the 1950s by the film company Kodak for medical imaging purposes. It is used in intravenous injections during liver function tests and is useful for diagnosing chronic hepatitis and liver cirrhosis.

The team confirmed the actual effectiveness of indocyanine green through animal experiments. In mice treated with indocyanine green, only 50% died after exposure to α-amanitin, compared to 90% mortality in the untreated control group, demonstrating a significant detoxifying effect. However, the researchers administered indocyanine green four hours after mushroom ingestion, whereas in humans, symptoms typically appear one to two days after ingestion, indicating a time lag that needs further investigation.

Indocyanine green has already been approved by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) as a medical imaging agent, confirming its safety for human use at certain doses. Accordingly, the Sun Yat-sen University team hopes to proceed with clinical trials soon to develop this into a pharmaceutical treatment.