Snakebite savior: CRISPR tech helps discover antidote for cobra venom

Scientists at the University of Sydney and the Liverpool School of Tropical Medicine have discovered that a commonly used blood thinner, heparin, can be repurposed as an antidote for cobra venom.

This finding has the potential to revolutionize snakebite treatment in regions where cobra bites are a significant health concern.

“Well the heparinoid drugs are already FDA approved at the dose we used and with the route of delivery we used, so if we can show this works in humans, then it will be very quick to have this therapy used,” said Professor Greg Neely, from the University of Sydney and a corresponding author of the study, to Interesting Engineering ( IE ).

Heparin’s potential to reduce necrosis and improve survival

Neely highlighted the potential impact of their discovery, stating, “Our discovery could drastically reduce the terrible injuries from necrosis caused by cobra bites – and it might also slow the venom, which could improve survival rates.”

The research team, which included scientists from Australia, Canada, Costa Rica, and the UK, used CRISPR gene-editing technology to identify human genes that cobra venom targets to cause necrosis.

They found that heparin and related drugs can block these targets, thus preventing necrosis.

Their findings demonstrate that heparin can act as a ‘decoy’ antidote, binding to and neutralizing the venom’s toxins.

CRISPR technology and the road to human trials

PhD student and lead author Tian Du emphasized the accessibility and potential of heparin, “Heparin is inexpensive, ubiquitous, and a World Health Organization-listed Essential Medicine. After successful human trials, it could be rolled out relatively quickly to become a cheap, safe, and effective drug for treating cobra bites.”

Elaborating on the use of CRISPR technology in their research Neely said to IE , “We used CRISPR to turn off every gene in the human genome in one big pool of cells, then added snake venom, which should kill every normal human cell.”

Then they sequenced the surviving cells to identify the human genes responsible for resistance. They discovered that cobra venom targets heparan and heparins. Using extra heparin, a common medicine, the researchers injected it at the snake bite site. In mice, this approach almost completely blocked local damage.

Moving from successful laboratory trials to human clinical trials requires significant funding.

“To get a clinical trial going, we next need to raise money, about 8 million dollars, which might be a challenge b/c cobra impacts some of the poorest areas in the world, but we are hoping we can get some interest from governments or philanthropic organizations to help us pay for the trial,” Neely told IE .

Addressing the challenges in low- and middle-income countries

Snakebites kill up to 138,000 people annually, with 400,000 more suffering long-term consequences. In regions like India and Africa, cobra species are responsible for many snakebite incidents.

The World Health Organization has prioritized snakebite in its program for tackling neglected tropical diseases, aiming to halve the global burden of snakebite by 2030.

“Snakebites remain the deadliest of the neglected tropical diseases, with its burden landing overwhelmingly on rural communities in low- and middle-income countries,” said Professor Nicholas Casewell from the Liverpool School of Tropical Medicine, co-author of the study, in the press release.

“Current antivenoms are largely ineffective against severe local envenoming, leading to painful progressive swelling, blistering, tissue necrosis, and lifelong disability.”

The heparin-based antidote represents a new class of therapeutic for cobra venom, addressing local tissue death at the bite site, unlike existing antivenoms.

Neely explained, “For cobras, the antivenoms used can be good at blocking the systemic effects of cobra venom, but they are not good at blocking the local tissue death at the site of the bite.”

Implementing this antidote in low- and middle-income countries poses challenges, primarily funding a clinical trial and ensuring the medicine reaches those in need.

“The main challenge is funding a clinical trial. Once that is complete, and if the trial is successful, then the next challenge is getting the medicine to people that need it. This probably entails having a health care practitioner in a rural setting learning how to inject the heparin or related molecule,” Neely noted, in the email to IE .

The team employed this method to discover an antidote for box jellyfish venom in 2019.

The research was published in Science Translational Medicine .