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Since CRISPR was introduced 14 years ago by Jennifer Doudna and Emmanuelle Charpentier, now Nobel laureates, the gene-editing breakthrough has been used to improve therapies for cancer, heart disease, and sickle cell anemia. Surprising applications for CRISPR are being found every year, including reviving veggies to feed a warming planet. Recently, scientists made the happenstance discovery that CRISPR could treat a life-threatening condition that seems torn from the pages of ancient mythology but is faced by millions today: cobra bites.
The fabled snake with the flaring hood is not just a menace to Indiana Jones. In fact, venomous snake bites are no laughing matter. Nearly 140,000 people are killed annually by venomous snakes and another 400,000 permanently disabled. When a cobra bites, the snake’s venom causes local swelling, severe pain, and eventually death of the tissues surrounding the bite area.
Because people who are bitten by cobras in the wild often live in rural, isolated areas of the tropics, “it could take them many, many hours to get to a health facility where they can receive treatment,” says Nicholas Casewell, who heads the Centre for Snakebite Research & Interventions at Liverpool School of Tropical Medicine. “It is not uncommon for people to present to the hospital with extensive swelling at that point of presentation and a lot of pain, and even tissue necrosis.”
The standard treatment is receiving an IV of antivenom, which must be refrigerated and given in a healthcare facility. And because cobras’ venom causes rapid damage to the tissues around the bite, time is of the essence.
So Casewell and his colleagues went looking in the human body to see if they could find better ways to block the damage done by these toxins. Using CRISPR, they tracked down the human genes that cause tissue death around the site of the bite. They knocked out genes in each of the skin cells in a culture while pouring liquid cobra venom onto them—enough to kill each individual cell. When some of the cells survived, they grew these cells in new cultures and then sequenced them, to see if they could find genetic markers that separated them from the rest. In those screens, they found heparan and heparin molecules. Heparin is released during an immune response, and heparan exists on the surface of the cell. Finding these cells led them to the drug heparin, which has been used since the 1930s. The drug decreases the blood’s clotting ability and helps prevent clots from forming in blood vessels. The findings were published recently in the journal Science Translational Medicine.
Cobras’ venom causes rapid damage to the tissues around the bite, so time is of the essence.
Before it can be used to treat cobra bites in the field, the scientists will need to test it further in clinical trials. But the fact that this discovery using CRISPR pointed them to a drug that is already common and has a solid safety record gives them hope—both for better treating cobra bites and for finding ways to block other snakes’ venoms.
In the past, Casewell says, the approach to developing antidotes for snake bites was to identify the chemical composition of a particular species’ venom, and then figure out how to block the specific toxins it contained. The CRISPR approach focuses not on the toxins but on the pathways the toxins use to create harm inside the body and kill cells.
Today, treatments for snake bites typically consist of antibodies derived from animals. To make them, scientists inject a donor animal—often a cow or sheep—with small quantities of snake venom, which creates an immune response. Then they take the antibodies from the donor animal’s blood plasma and concentrate them.
Antivenoms are lifesavers, but they have a lot of limitations, Casewell says: In addition to having to be refrigerated and administered in the clinic, they are also expensive and have limited efficacy to specific snakes. “If you make an antivenom against a rattlesnake, for example, it’s not going to help for a cobra snake bite,” he says.
The researchers imagine that in the future—if clinical trials are successful—heparin could be stored in villages, in auto-injection pens for cobra bites. And hopefully the approach could be replicated to find other broad-acting, simpler treatments for other venomous snake types.
“It is really excellent research,” says Bryan Fry, a venom expert at the University of Queensland in Australia who wasn’t involved in the new study. Fry agrees that heparin’s flexibility means it could save many more people from life-threatening injury since it could be stored in rural “doc-in-a box” kits that can be delivered directly to those areas where people are most at risk.
Greg Neely, a geneticist at the University of Sydney in Australia and a coauthor of the cobra paper, plans to study vipers next, which, like cobras, can cause substantial tissue damage and death with their venom—but have different toxins in their venoms. He’s starting to see patterns in the ways venom does its dirty work, which could lead scientists to antidotes that can treat a wider range of bites. He says he has a healthy respect for venoms, but also a passion for disarming their power: “If we can figure out how venom works a bit, it can teach us something,” he says.
Neely says CRISPR is an extraordinary tool of discovery for researchers. He describes CRISPR experiments as “flipping switches and seeing what lights up.” 
Lead image by Butusova Elena and Ilya Lukichev / Shutterstock
*An earlier version of this story mislabeled venomous snakes as poisonous. The story has been revised accordingly.
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