Scientists engineer hookworms to deliver medicine

Scientists have genetically engineered hookworms to produce therapeutic molecules inside the body, taking a significant step toward using parasites as living drug factories for chronic diseases.

The proof-of-concept study, published in Nature Communications, used CRISPR gene-editing technology to modify human hookworms so they produced an antibody capable of neutralising a deadly toxin. Although still in its early stages, the research raises the possibility that engineered parasites could one day continuously deliver medicines for conditions ranging from autoimmune diseases to obesity, eliminating the need for daily pills or injections.

The work was led by researchers at Washington University School of Medicine in St. Louis, who say a small number of harmless, engineered hookworms could eventually function as an “internal pharmacy.”

“Taking medications every day can be difficult for many patients with chronic illnesses,” said molecular geneticist Dr. Makedonka Mitreva, who led the research. “What if every person at risk of chronic disease carried their own pharmacy inside them?”

Hookworms naturally live in the human intestine, where they can survive for years. According to the researchers, carefully controlled numbers — perhaps around 50 worms — could release therapeutic proteins into the bloodstream without causing significant harm to their host.

To test the idea, the team genetically modified Ancylostoma ceylanicum, a hookworm species capable of infecting humans. Because adult hookworms are protected by a tough outer coating, researchers instead collected hookworm eggs and used a technique called electroporation, which briefly applies electricity to create tiny openings in cell membranes, allowing gene-editing tools to enter.

Using CRISPR-Cas9, the scientists inserted genetic instructions enabling the worms to produce an antibody fragment against tetrodotoxin, a powerful neurotoxin found in pufferfish that currently has no antidote. The project received funding from the US Defense Advanced Research Projects Agency (DARPA), which is interested in developing countermeasures against toxins that could potentially be used as biological weapons.

The engineered hookworms were then introduced into hamsters. Blood tests confirmed that the modified parasites released antibody fragments into the animals’ circulation.

While the antibodies were able to neutralise around 20 per cent of the toxin in laboratory tests, the amount produced would probably not be enough to protect animals exposed to lethal doses of tetrodotoxin.

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Independent experts say the findings should therefore be viewed primarily as a demonstration that genetically modified hookworms can manufacture and secrete therapeutic proteins inside a living host.

“The fact that the researchers could successfully introduce DNA into hookworm eggs opens the possibility of applying this technology to many other parasitic worms,” said Professor Elissa Hallem, a parasitologist at the University of California, Los Angeles, who was not involved in the study.

Such advances could not only improve scientists’ understanding of parasite biology but also lead to entirely new drug delivery systems.

However, several challenges remain before engineered hookworms could be used in people. Researchers must ensure the inserted genes remain stable over multiple generations and significantly increase the amount of medicine each worm can produce to achieve clinically useful doses.

Mitreva’s team is already working to optimise therapeutic protein production so that relatively few worms could deliver enough medication to treat disease.

Experts say the concept may sound like science fiction, but the latest study suggests it is becoming scientifically plausible.

“It’s moving a bit from science fiction to science,” said Professor Cornelis Hokke, a parasitic infectious disease specialist at Leiden University Medical Center in the Netherlands.

Although human use remains years away, the research represents an important milestone in the development of living medicines that could one day provide continuous treatment from inside the body.