Using genomic editing tools, researchers may have found a way to create an antidote to the sting of one of the Earth’s most dangerous animals.
A team from the University of Sydney has discovered an antidote to the venomous and possibly fatal sting of the Australian box jellyfish (Chironex fleckeri), which carries enough venom to kill more than 60 humans.
After studying how the deadly sea creature’s venom actually works using CRISPR genome-editing techniques, the researchers found a treatment that blocks the symptoms of a box jellyfish sting if it is administered to the skin within 15 minutes of contact.
“We were looking at how the venom works, to try to better understand how it causes pain,” Greg Neely, an associate professor at the Charles Perkins Centre at the University of Sydney, said in a statement. “Using new CRISPR genome editing techniques we could quickly identify how this venom kills human cells. Luckily, there was already a drug that could act on the pathway the venom uses to kill cells, and when we tried this drug as a venom antidote on mice, we found it could block the tissue scarring and pain related to jellyfish stings. It is super exciting.”
In the study, the researchers looked at millions of human cells and after exposing the cells to venom from a box jellyfish, looked for which cells survived. According to the study, they then screened for host components required for venom exposure-induced cell death using genome-scale lenti-CRISPR mutagenesis.
They identified the peripheral membrane protein ATP2B1, a calcium transporting ATPase, as one host factor required for venom cytotoxicity. By targeting this protein, they were able to prevent venom action and confer long lasting protection.
The researchers successfully injected the antidote on both human cells outside the body and live mice and hope to eventually develop a topical application in spray or cream form that is effective on humans. The researchers ultimately looked at the cells that survived and identified the human factors that are required for the venom to work from the whole genome screening.
“The jellyfish venom pathway we identified in this study requires cholesterol, and since there are lots of drugs available that target cholesterol, we could try to block this pathway to see how this impacted venom activity,” Raymond Lau, PhD, the lead author of the study, said in a statement. “We took one of those drugs, which we know is safe for human use, and we used it against the venom, and it worked. It’s a molecular antidote.
“It’s the first molecular dissection of how this type of venom works, and possible how any venom works,” he added. “I haven’t seen a study like this for any other venom.”
A single sting cause skin necrosis, excruciating pain and possible cardiac arrest and death within minutes if the dose of venom is large enough.
“We know the drug will stop the necrosis, skin scarring and the pain completely when applied to the skin,” said Neely, who is the senior author on the paper. “We don’t know yet if it will stop a heart attack. That will need more research and we are applying for funding to continue this work.”
The Australian box jellyfish, which is primarily found in coastal waters in northern Australia and the waters around the Philippines, has about 60 tentacles that can grow up to three meters long and is filled with millions of microscopic hooks containing venom. They can actively swim, rather than floating like other jellyfish, at speeds up to 4.5 miles per hour through shallow waters when they are hunting for small fish and prawns.
Currently, treatments for box jellyfish sting include an anti-venom generated in sheep, although the effectiveness of this anti-venom remains in question, according to the researchers. Some studies have shown that venom can also be suppressed by intravenous zinc or by heating the site of the sting. However, there are currently no therapies that directly target pain and local tissue necrosis, the most common target for treating venom. The major obstacle to developing new therapies is the limited molecular understanding of venom action, a prerequisite for more rational therapies.
The researchers are now seeking potential partners to make the medicine publicly available.
The study was published in Nature Communications.