A deadly antidote to jellyfish discovered using CRISPR genome modification

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Researchers at the University of Sydney have discovered an antidote to the deadly bites inflicted by the most venomous creature on the planet, the Australian jellyfish.

The Australian jellyfish (Chironex fleckeri) has about 60 tentacles up to three meters long. Each tentacle has millions of microscopic hooks filled with venom.

Each jellyfish contains enough venom to kill more than 60 humans.

A simple bite in humans will cause skin necrosis, excruciating pain and, if the dose of venom is large enough, cardiac arrest and death within minutes.

Associate Professor Greg Neely and Dr. Raymond (Man-Tat) Lau and their team of researchers in pain research at the Charles Perkins Center of the University of Sydney were studying the operation of canned jellyfish venom when they made this discovery.

They found a drug that blocks the symptoms of a canned jellyfish sting if administered to the skin within 15 minutes of contact.

The antidote has been shown to act on human cells external to the body and then effectively tested in live mice.

The researchers are now hoping to develop a topical application for humans.

"We were looking at how venom works to better understand how it causes pain, and with new CRISPR genome modification techniques we could quickly identify how this venom kills human cells." Fortunately, there was already a drug that could 39, act on the path taken. " venom uses to kill cells, and when we tried this drug as a venom antidote on mice, we found that it could block tissue healing and the pain associated with jellyfish stings, "said the associate professor. Neely. "It's super exciting."

Posted in Nature Communications Today, the study used the CRISPR edition of the entire genome to identify how venom works. Genome editing is a technology that allows scientists to add, delete or modify genetic material in an organism's DNA.

In the study, the researchers took a vat of millions of human cells and inoculated a different human gene into each of them. Then they added the jellyfish venom (which kills the cells in high doses) and searched for surviving cells. From the screening of the entire genome, the researchers identified the human factors necessary for venom function.

"The jellyfish venom path we identified in this study requires cholesterol, and since there are many drugs available to target cholesterol, we could try to block this pathway to see how this impacts venom activity. We took one of these drugs, which we know well, is safe for human use, and we used it against venom, and it worked, "said Dr. Lau, author main document. "It's a molecular antidote."

"It's the first molecular dissection of how this type of venom works and how any venom works," Dr. Lau said. "I have not seen any study like this for another venom."

"We know that the drug will completely stop necrosis, skin scarring and pain when applied to the skin," said Associate Professor Neely, who is the lead author of the paper. "We do not know yet if this will stop a heart attack, it will require more research and we are asking for funding to continue this work."

Present in the coastal waters of northern Australia and in the waters around the Philippines, the jellyfish box is extremely dangerous. They do not just float, they can actively swim and gain a speed of 7.5 km / h when they hunt. They feed in shallow waters, mainly small fish and shrimp.

There are two types of jellyfish, the Irukandji, which is tiny, and the Chironex fleckeriwhich is about three meters long. "We've studied the biggest, the most venomous and scary," said Associate Professor Neely. "Our drug is working on the big beast, we do not know yet if it works on other jellyfish, but we know it works on the most deadly."

The venom used in this study was collected in a box of jellyfish off the waters of Cairns by Associate Professor Jamie Seymour of James Cook University.

Anecdotal evidence suggests that the only current treatment against a sting is to spray the area with vinegar for 30 seconds or to let very hot water over the affected area for 20 minutes. If this is a major problem, continuous CPR is needed for the heart to continue beating.

"Our antidote is a drug that blocks venom," said Associate Professor Neely. "You have to put it on the site within 15 minutes.In our study we have injected it.But the plan would be a spray or a topical cream.The argument against a cream is that when you are stung If you apply cream on it, you risk getting more venom in. But if you spray, you could neutralize what's left outside your body. "

Associate Professor Neely and his team are now looking for potential partners to make the drug available to the public.

Associate Professor Neely's team is working in functional genomics and studying chronic pain at the Charles Perkins Center. He also directs the Sydney Genome Editing Initiative of the University of Sydney. They study a range of deadly Australian creatures – the jellyfish box and a wide variety of other venomous animals – to understand what causes the pain.

In 2018, pain and chronic pain cost the Australian economy $ 139 billion and are headed for $ 215 billion by 2050, according to Pain Australia.

"Most of our work is focused on developing non-addictive painkillers for humans," said Associate Professor Neely. "One of the ways to do that is to understand how the painful venom of Australian creatures works by using the all-new CRISPR technology – it's super cool."