Antidote to deadly jellyfish identified using CRISPR

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Box jellyfish antidote CRISPR
Scientists at the University of Sydney have identified an antidote using CRISPR to the deadly sting provided by the most poisonous animal on the planet-- the Australian box jellyfish.

Australian researchers have identified the molecular pathway of how a jellyfish venom works

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he Australian box jellyfish (Chironex fleckeri) has around 60 tentacles that can easily develop to three meters in length. This jellyfish populates waters across the tropical Top End of Australia’s Northern Territory. Every tentacle has thousands of minuscule hooks loaded with toxin.

Associate Professor Greg Neely and Dr. Raymond (Man-Tat) Lau and their group of pain scientists at the Charles Perkins Centre at the University of Sydney were researching the way the box jellyfish toxin functions when they observed the finding. “Box jellyfish venom hurts really, really, really badly, and we didn’t understand how it works, so we started from that angle, of trying to figure out how the pain works,”, said Associate Professor Greg Neely.

While box jellyfish antivenom currently exists and is available in the Northern Territory and Queensland medical facilities, this research has been celebrated as “the first molecular dissection of how this type of venom works, and possibly how any venom works”.

The new antidote prevented tissue scarring and pain related to jellyfish stings

They revealed a drug that prevents the manifestations of a box jellyfish sting if provided to the skin just within 15 minutes after touch. The antidote was proven to function on human cells away from the human body and then examined successfully on living rodents. Scientists now intend to create a topical application for humans.

Using new CRISPR genome editing techniques we could quickly identify how this venom kills human cells

“We were examining the way the toxin functions, to attempt to better comprehend how it induces pain. Employing new CRISPR genome editing approaches we could rapidly determine how this toxin eliminates human cells. Fortunately, there was currently a drug that could act upon the pathway the toxin uses to eliminate cells, and when we attempted this drug as a toxin antidote on rodents, we found it could prevent the tissue scarring and pain related to jellyfish stings,” mentioned Associate Professor Neely. “It is super impressive.”

Published in the journal Nature Communications on April 30th, the investigation used CRISPR whole genome editing to determine the way the toxin functions. Genome editing is a technology that enables researchers to add, get rid of or modify genetic content in an organism’s DNA.

Cholesterol is needed by the jellyfish toxin pathway

In this research study, the scientists used a container of millions of human cells and knocked out a unique gene in each one. After that, they included the box jellyfish toxin – which eliminates cells at high concentrations – and searched for cells that made it through. From the entire genome screening, the scientists found human factors that are needed for the toxin to function.

“The jellyfish toxin pathway we discovered in this particular research study needs cholesterol, and given that currently there are plenty of drugs to choose from that target cholesterol, we could attempt to prevent this pathway to see how this affected toxin activity. We utilized one of those drugs, which we know is nontoxic for human use, and we employed it against the toxin, and it did the job,” said Dr. Lau, who is the primary author on the report. “It’s a molecular antidote.”

“It’s the very first molecular investigation of how this variety of toxin functions, and plausible how any kind of toxin functions” Dr. Lau mentioned. “I haven’t seen a research study similar to this for any other toxin.”

“We know the drug will prevent the necrosis, skin scarring and the pain entirely when applied to the skin,” mentioned Associate Professor Neely, who is the senior author on the study.

We don’t understand yet if it will prevent a cardiac arrest. That will require further investigation and we are requesting funding to carry on this task

The venom from the box jellyfish is incredibly harmful

Discovered along the coast in northern Australia and into the waters all around the Philippines, the box jellyfish is incredibly harmful. They don’t simply float, they can proactively dive, achieving a speed of 7.5 kilometers an hour when they are hunting. They feed in shallow waters, primarily small fish and shellfishes.

There are a couple of types of box jellyfish, the Irukandji, which is small, and the Chironex fleckeri, which is about three meters long. “We examined the biggest, most poisonous and frightening one,” said Associate Professor Neely. “Our drug works on the large creature. We don’t understand yet if it works with other jellyfish, but we know it functions on the most-deadly one.”

The toxin employed in the research was collected from a box jellyfish off the waters of Cairns by Associate Professor Jamie Seymour at James Cook University.

Box jellyfish beach sign
In the north of Australia, people are regularly warned not to swim when box jellyfish are around. CREDIT: AUSCAPE /GETTY IMAGES

Can a jellyfish’s sting kill you?

A single sting to a human will trigger necrosis of the skin layer, agonizing pain and, if the amount of toxin is big enough, heart failure and death in just minutes.

Historical evidence indicates the only existing remedy for a sting is soaking the area with vinegar for 30 seconds or running extremely hot water over the damaged area for 20 minutes. If it’s a significant sting, continuous CPR is required to maintain the heart beating.

“Our antidote is a drug that prevents the toxin,” mentioned Associate Professor Neely. “You need to receive it onto the site within 15 minutes. In our research, we infused it. But the strategy would certainly be a spray or a topical lotion. The issue against a lotion is when you are stung it leaves behind huge amounts of small stingers in you so if you apply the lotion on it might be pressing more toxin into you. However, if you spray, it could neutralize what’s left outside of your body.”

Associate Professor Neely and his group are currently searching for prospective partners to focus on making the medicine accessible to the public. The team specializes in functional genomics and research in chronic pain at the Charles Perkins Centre where Neely leads the Sydney Genome Editing Initiative at the University of Sydney. They are studying a range of deadly Australian creatures– the box jellyfish, and a variety of other poisonous animals– to learn about what triggers pain.

In 2018, pain and chronic pain cost $139 billion to the Australian economy and is heading towards $215 billion by 2050, according to Pain Australia.

“The majority of our job is directed at making non-addictive pain medication for people,” mentioned Associate Professor Neely. “One approach we accomplish this is to identify how painful toxins from Australian creatures function employing brand new CRISPR technology. It is super amazing.”

Source

Man-Tat Lau, John Manion, Jamie B. Littleboy, Lisa Oyston, Thang M. Khuong, Qiao-Ping Wang, David T. Nguyen, Daniel Hesselson, Jamie E. Seymour, G. Gregory Neely. Molecular dissection of box jellyfish venom cytotoxicity highlights an effective venom antidote. Nature Communications. Published online Apr 30, 2019. doi: 10.1038/s41467-019-09681-1