For millions living in rural, tropical regions, the threat of a snakebite is a constant shadow. The World Health Organization (WHO) notes that about 4.5–5.4 million people get bitten by snakes annually. Of this, 1.8–2.7 million develop clinical illness, and 81,000 to 138,000 die from complications.

The only specific treatment for decades has been antivenom. While effective against the systemic, lethal effects of venom in the bloodstream, conventional antivenoms often fail to prevent severe local tissue damage at the bite site, leading to paralysis, amputations, and lifelong disability.

Building on the global success of mRNA-LNP (lipid nanoparticle) technology during the Covid-19 pandemic, scientists are now exploring its potential to tackle snake venom directly. A fresh contribution to this evolving field comes from researchers at the University of Reading, led by Professor Sakthi Vaiyapur. The study published in Trends in Biotechnology, authored by Professor Vaiyapur and Professor Andreas Laustsen from the Technical University of Denmark, demonstrated for the first time that mRNA can be used to express toxin-neutralizing antibodies directly in muscle tissue, preventing venom-induced damage in preclinical models.

In an interview with the Drug and Device World, Professor Vaiyapuri, the study’s co-author, delves into these promising early results, exploring how this technology could be deployed, its potential to become a broad-spectrum antidote, and the challenges that lie ahead on the path from the lab to the field.

Why mRNA-Encoded Antitoxins?

The core concept is elegant in its simplicity: rather than manufacturing antibodies in animals or bioreactors and then injecting them, why not instruct the patient’s own cells to produce them locally and on demand?

Professor Vaiyapuri’s team designed an mRNA sequence that codes for a single-chain variable fragment (scFv) – a compact version of an antibody – specifically targeting a myotoxin (M-II) from the venom of the lancehead viper, Bothrops asper. This toxin is known to cause extensive skeletal muscle damage that antivenoms cannot stop.

“In this research, we tested this only for local envenomation effects,” explains Vaiyapuri, referring to the damage at the bite site. “But it doesn’t mean that it won’t work for systemic envenomation. As soon as the antibodies are expressed in local tissue, they will get into the bloodstream, and they can neutralize the toxins in the bloodstream as well. But we haven’t tested that part.”

Their research, detailed in the paper, showed that human muscle cells in a lab dish, transfected with these mRNA-LNPs, began producing the protective scFvs within 24 hours. When subsequently exposed to the pure myotoxin or the whole B. asper venom, these “armed” cells showed significantly reduced damage compared to untreated cells. This proof of concept was then successfully replicated in mice, where a single intramuscular injection of the mRNA-LNPs protected against muscle damage caused by a subsequent toxin challenge.

Professor Vaiyapur highlights the significance: “This is not just a lab curiosity — the fact that we see robust tissue expression and toxin neutralization suggests a real clinical potential. For example, in regions where snakebite or venom exposure remains a major health risk, this could offer a faster, more accessible therapeutic option.”

Overcoming the “Acute Problem

A logical question is whether this approach could be used prophylactically, like a vaccine, for those at the highest risk. Professor Vaiyapuri is quick to dismiss this idea, citing the fundamental nature of snakebite envenoming.

“For years I’ve been working on this area… From the beginning, we were asking why can’t we develop some vaccines for snakebites, but practically it’s not possible,” he says. “Snakebite is an acute problem. In some cases, snakebites can kill people within a few hours… So, because it’s an acute problem, we need to fight this immediately.”

He explains that a traditional vaccine primes the immune system to produce its own antibodies over days or weeks, a timeline utterly mismatched with the rapid action of venom toxins. The mRNA approach described here is not a vaccine but a reactive treatment – a therapeutic administered after the bite has occurred to generate a rapid, localized defense.

“The body cannot produce antibodies naturally when given a vaccine because it takes at least 48 hours to produce a peak level of antibodies… So, we thought, maybe that may not work as a prophylactic mechanism. But can we do it the other way around? As a reactive response? As soon as the bite has happened, someone is visiting a health facility in rural areas where we can just inject this in the local bite site. That’s where most of the venom will be stored.”

Challenges and Caveats

Despite the promise, Professor Vaiyapur is quick to caution that there are substantial challenges before this approach can become a mainstream therapy.

“We need to thoroughly assess immune responses, long-term expression, and off-target effects — especially if we’re targeting toxins in sensitive tissues, or if repeated dosing is necessary,” he says.

Moreover, although mRNA offers faster development cycles than traditional biologics, manufacturing, storage, and cold-chain logistics — particularly in low-resource regions — remain nontrivial. However, Professor Vaiyapuri notes that it’s not impossible, as proven by the successful Covid-19 vaccination drives, even in rural settings.

“The Covid vaccine had been given in every Primary Health center everywhere… The concept here is, why don’t we use the same approach to store these mRNAs locally in the rural areas? So as soon as the bite has happened, they will get this jab, then they will continue to travel to a tertiary care hospital where they can seek antivenoms as required.”

Optimizing the Dose and Expanding the Arsenal

The study also tackled a crucial practical consideration: dosage. The researchers found that the relationship between mRNA concentration and antibody production is not linear. While lower concentrations (1-2.5 µg/ml) successfully produced protective scFvs, a high concentration (5 µg/ml) became toxic to the muscle cells, actually reducing antibody expression.

“So when we go for a very high concentration… It’s becoming toxic,” Vaiyapuri confirms. This optimization will be essential for future clinical trials to find a dose that is both safe and effective for adults and children.

Perhaps the most ambitious goal is to move beyond a single-toxin solution. Snake venoms are complex cocktails of dozens of different toxins, primarily falling into a few key families: metalloproteases, phospholipase A2, and three-finger toxins.

“We tested this against only one toxin… But in the future, we need to come up with all the important toxins,” says Vaiyapuri. The vision is to create a cocktail of mRNA sequences, each coding for an scFv that targets a conserved region common across a major toxin family in many different snake species.

“If you look at their sequences, there are quite a lot of similarities between them. So, we need to develop antibodies against the particular regions that are similar across different snakes… Then you mix them all together as like a mixture of different mRNAs… that could be potentially used for any snake across the world.”

Where the Research Could Go Next

Despite the exciting proof-of-concept, Professor Vaiyapuri is clear that this is not a treatment that will be available tomorrow. He estimates a development timeline of 5 to 10 years. Key challenges remain, including further reducing the time needed for the body to produce sufficient antibodies (currently 12-24 hours in models) and solving the cold-chain storage requirements for mRNA in remote locations.

However, confidence from this initial data is palpable. “This is really exciting, seriously, because everyone thought only the antibody approach would work for snakebites… But this approach is unique. Nobody has thought about this,” he says.

The key takeaway, he stresses, is that a door once thought closed is now open. “So far, everyone thought that this technology would not be useful. We cannot really go with the vaccine technology for a snakebite because it’s an acute problem. For the first time, we are saying yes, it can work, we just need to spend more time on it, more money on it, and see whether this can be developed as a universal antidote approach for snakebites.”