Coming from Scandinavia, Anne Ljungars admits she had never given much thought to snakebite envenoming. “Is that even a problem?” she told DDN, recalling her initial reaction when she first encountered the field. In Sweden or Denmark, snake envenoming barely registers as a public health concern. Globally, however, it is a very different story.
That’s why it hasn’t been solved already. If it had been a Western problem, it would have been solved by now.
—Anne Ljungars, Technical University of Denmark
Each year, more than 100,000 people die from snakebite envenoming, and many more are left with lifelong disabilities, including amputations and severe tissue damage. The burden falls overwhelmingly on rural, low-income regions, particularly in sub-Saharan Africa and South Asia. “That’s why it hasn’t been solved already,” she said. “If it had been a Western problem, it would have been solved by now.”
Ljungars is a Senior Scientist at the Technical University of Denmark, with a background in antibody discovery and characterization for therapeutic use. Her entry into snakebite research came through an academic group focused on venom biology and antivenom development — a field that, despite its impact, has seen remarkably little technological disruption over the past century.
Now, her latest research points to a potential shift in how antivenoms are manufactured, making production simpler, more cost-effective, and far more accessible where snakebite burden is highest.
A therapy stuck in the past
The biggest obstacle to surviving a snakebite is limited access to high-quality antivenom. The standard antivenoms used today are produced using methods that date back more than 120 years. Venom is collected from snakes and injected, in increasing doses, into large animals such as horses. Over time, the animals develop antibodies against the venom. Blood is then drawn, and antibody-rich plasma is purified and administered to snakebite patients.
The approach works — it saves lives every day — but it comes with significant drawbacks. Because the antibodies come from another species, patients are exposed to large amounts of foreign proteins, increasing the risk of severe immune reactions. The process is expensive, labor-intensive, and difficult to standardize. It also depends on maintaining colonies of both snakes and horses, and on repeatedly re-immunizing animals to generate new batches.
“It’s essentially like getting a blood transfusion from a horse,” Ljungars said.
Venom complexity adds another layer of difficulty. Snake venoms are not single toxins but complex mixtures, containing dozens of components at varying abundances. Different species — and even individual snakes — produce different venom profiles. To cover a broad range of bites, manufacturers often need venoms from multiple species, and the immune response in animals can vary unpredictably from batch to batch.
The result is a system that is costly, variable, and poorly suited to the regions where snakebite is most common.
A new kind of antivenom
In parallel with the manufacturing challenge, Ljungars and her colleagues have been rethinking what an antivenom could look like. In earlier work, published in Nature, the team showed that a defined mixture of eight nanobodies could neutralize venom from 17 out of 18 medically relevant snake species in Africa. The cocktail protected mice not only from death, but also from the local tissue damage that often leads to amputations.
This works because each nanobody targets an entire class of toxins rather than a single molecule. “For example, short neurotoxins interfere with the nerve signals that control muscle contraction, leading to paralysis, and are shared across many snake species. If one antibody can neutralize all of those, and another nanobody covers another toxin family across multiple snake families, you can build a single antivenom with broad effectiveness without needing to know exactly which snake caused the bite,” said Ljungars.
This is extremely important as most people often don’t know which snake bit them. Instead, clinicians must infer the species based on symptoms — which can overlap — and delay treatment until those symptoms appear. A broad-spectrum antivenom could simplify care, reduce reliance on specialist expertise, and enable earlier intervention.
However, to be viable in places like sub-Saharan Africa, antivenom needs to be inexpensive and straightforward to manufacture, with infrastructure that can be set up in multiple regions.
The cocktail problem
In conventional biologics manufacturing, combination therapies are produced one component at a time. Each antibody requires its own production vessel, its own purification process, and its own quality control. As more components are added, the costs and complexity scale linearly.
“For cocktails, this quickly becomes impractical,” Ljungars said. “The more nanobodies you add, the more expensive and complicated the end product becomes.”
This manufacturing bottleneck is not unique to antivenoms. Across cancer, infectious disease, and antiviral therapy, multi-antibody approaches are increasingly attractive — but often prohibitively expensive to produce.
A one-pot approach
The breakthrough described in Stargardt’s and Ljungars’ latest study now seems obvious. Instead of relying on the industry standard of producing antibodies one by one in Chinese hamster ovary (CHO) cells, the team worked with enGenes Biotech to co-cultivate multiple engineered Escherichia coli strains in a single bioreactor, producing an entire nanobody cocktail in one go.
Importantly, these E. coli cells were growth-decoupled. This means their normal cycle of growth and division was separated from the production of the therapeutic proteins. Once the bacteria reached a set population, they effectively stopped prioritizing replication and instead channeled their resources into making nanobodies. This separation helped stabilize the system, preventing faster-growing strains from outcompeting others, and making it far easier to control the final composition of the cocktail.
In practice, each snake injects a different amount of venom, and that varies between species and even between individuals depending on age, diet, and other factors.
—Anne Ljungars, Technical University of Denmark
The harder part was maintaining an exact ratio between components, but in the case of snakebite treatment, absolute precision is not always necessary. “In practice, each snake injects a different amount of venom, and the composition varies between species and even between individuals depending on age, diet, and other factors. So, it’s always an approximation rather than a precise formula,” Ljungars said.
Why bacteria beat hamster cells
The one-pot approach simplifies production and also substantially reduces cost compared to conventional antibody manufacturing in CHO cells. CHO-based production requires long culture times, typically around ten days per batch, as well as complex media, stringent sterility controls, and extensive downstream purification steps. By contrast, bacterial fermentation runs are faster — around 48 hours in this study — and require much less specialized infrastructure. The media is cheaper, the process is more scalable, and downstream purification is more straightforward, particularly because bacteria do not require the same viral safety steps as mammalian cells.
The team modeled the economic implications of this shift using published cost frameworks for recombinant antibody production. Across a range of realistic yields and recovery rates, E. coli–based manufacturing was estimated to cost roughly $12–119 per gram, compared with $57–199 per gram for CHO-based systems.
When translated into a full treatment, these differences became even more apparent. Assuming a typical snakebite requires between 0.4 and 2 grams of nanobody-based therapeutic, the total manufacturing cost per dose is estimated at approximately $31–137 for the bacterial one-pot approach. By comparison, an equivalent antibody-based antivenom produced in CHO cells is estimated at around $261 per treatment.
This manufacturing strategy could make complex biologic therapies significantly more accessible in the regions where they are most urgently needed.
Beyond snakebite
While snakebite remains the immediate focus, Ljungars sees broader implications. “The real takeaway is that this approach could be applied much more broadly than snakebite,” she said.
Combination biologics are becoming increasingly common, whether to prevent viral escape, target multiple pathways, or improve durability. If multiple components can be reliably produced in a single, scalable process, therapies that are currently too expensive or too complicated to manufacture may become more realistic to deploy at scale.
For now, the next steps are pragmatic. The team is working toward larger-scale production, further validation, and ultimately animal studies in larger models before any clinical translation. Funding and infrastructure will determine how quickly the work progresses.
But the direction is clear. A field that has relied on largely unchanged methods for more than a century may now be approaching a turning point — away from horses and complex, fragmented manufacturing, and towards a single, unified process.
