Gene-editing technique might have finally cracked the mystery of how death cap mushrooms kill
to find an antidote for jellyfish venom. They first used CRISPR-Cas9 gene-editing technology to create a pool of human cells, each with a mutation in a different gene. They then tested which mutations helped the cells to survive exposure to α-amanitin.
This ‘CRISPR-Cas9 screen’ revealed that cells lacking a functional version of an enzyme called STT3B are able to survive α-amanitin. STT3B is part of a biochemical pathway that adds sugar molecules to proteins. Interrupting this pathway somehow blocks α-amanitin from entering cells, preventing the toxin from fully wreaking havoc.
The second step in the researchers’ strategy had them sifting through about 3,200 chemical compounds, looking for one that would block the action of STT3B. Among those compounds, they uncovered indocyanine green, a dye developed by the photography company Kodak in the 1950s that has since been used in medical imaging, for example, to visualize blood vessels in the eye and blood flow in the liver.
Researchers are excited about this method for finding antidotes, which is “very modern”, says toxicologist Jiří Patočka at the University of Southern Bohemia in České Budějovice, in the Czech Republic. Bode thinks similar experiments could identify antidotes for bacterial toxins that cause sepsis, which is currently difficult to treat.The US Food and Drug Administration and the European Medicines Agency have already approved indocyanine green for use in imaging.
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