There is a reason why it is not advisable to eat wild mushrooms; Amanita Amanita phalloides 2011 G3phalloides, nicknamed death cap mushrooms, closely resemble edible mushroom variants—but are deadly if ingested. If a person chances upon one and happens to eat it, regardless of whether it is cooked, there is a high likelihood that they die.

A. phalloides are the most toxic of any mushroom species and are responsible for the majority of fatal mushroom poisonings. Notable victims of death cap mushroom poisoning include Roman Emperor Claudius, Pope Clement VII, and Holy Roman Emperor Charles VI. A. phalloides poisoning has always been difficult to diagnose and even more difficult to treat, as symptoms emerge after a long delay and there has been no known antidote to A. phalloides toxin—that is, until researchers utilized CRISPR-Cas9.

Death cap mushrooms contain the amatoxin alpha-amanitin. The amatoxins are a group of toxins that share the trait of inhibiting the enzyme RNA polymerase II. In our AP Biology class, we discussed DNA polymerases and their vital function in DNA replication. Similarly, RNA polymerases are a vital component of RNA transcription and synthesis. RNA polymerase II synthesizes mRNA, the template for protein synthesis. Upon the inhibition of RNA polymerase II, cell metabolism comes to a halt and apoptosis (cell self-destruction) ensues.

Alpha-amanitin is possibly the most deadly of the amatoxins. The particular human genes that are triggered by alpha-amanitin were previously unknown, but CRISPR recently revealed these genes, one of which produces the protein STT3B. STT3B is a required component of alpha-amanitin toxicity, therefore an inhibitor of STT3B would negate the effects of alpha-amanitin.

Researchers found just that—an inhibitor of STT3B, indocyanine green. Once the effectiveness of indocyanine green was confirmed in vitro, scientists experimented with a mouse model of alpha-amanitine poisoning and found that indocyanine green had a profound effect if given one to four hours after ingestion of the toxin. However, if eight to 12 hours had elapsed before the indocyanine green was introduced, its effectiveness was greatly reduced, possibly because irreversible organ damage had already occurred in the subject. This fact poses concern, as alpha-amanitine poisoning symptoms take at least six hours to occur after A. phalloides ingestion.

While more investigation needs to be undertaken before indocyanine green can be proposed as a treatment for death cap mushroom poisoning, these latest discoveries represent a significant advancement in our understanding of the process. Any thoughts regarding CRISPR or this topic as a whole are encouraged.

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