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Scientists have genetically modified a parasite to produce antitoxins within its host. (Image credit: Stocktrek Images via Getty Images)Share this article 0Join the conversationFollow usAdd us as a preferred source on GoogleSubscribe to our newsletter
Researchers have genetically engineered a minuscule, worm-like parasite to generate a life-saving antitoxin from within a living organism.
In a pioneering study, scientists altered the hookworm Ancylostoma ceylanicum to produce antibodies that can partially neutralize the potent tetrodotoxin found in pufferfish.
The method has, to date, been evaluated in hamsters, with the ultimate objective of applying it to humans. The U.S. Department of Defense funded the research with the intention of developing protective measures for military personnel who might be exposed to threats like tetrodotoxin, whether chemical or biological, as explained by Alex Loukas, a co-author of the study and director at the Australian Institute of Tropical Health and Medicine, James Cook University, to Live Science.
Furthermore, subsequent research could involve engineering these worms to produce a variety of other medications and release them inside the human body, as indicated by the study’s authors in a publication on June 3 in Nature Communications. For instance, they might offer long-term remedies for chronic conditions such as type 2 diabetes or inflammatory bowel disease, Loukas suggested.
From parasite to antitoxin factory
Hookworms represent one of the most ancient parasites affecting humans, infecting over 400 million individuals globally, predominantly in tropical zones. These small intestinal worms, akin to internal leeches, attach to the gut lining to absorb blood, concurrently releasing various anti-inflammatory and immunosuppressive agents to evade expulsion by the body.
Each worm measures approximately 0.4 inches (1 centimeter) in length and consumes less than two drops of blood daily; healthy hosts often exhibit no symptoms of infection. The specific hookworm utilized in this research, A. ceylanicum, can infect humans, canines, and felines.
“The hookworm has evolved over millions of years to perfect its long-term survival within a human host and its ability to transfer molecules from its body to ours,” stated Makedonka Mitreva, a professor at Washington University School of Medicine in St. Louis, Missouri, and a co-author of the study.
The combination of compounds naturally produced by these parasites has already demonstrated potential in treating metabolic conditions like metabolic syndrome and type 2 diabetes, as well as celiac disease. However, previous investigations have been limited to naturally occurring molecules from the hookworms.
The current research advances this concept further. “We posed the question: What if we could introduce an additional molecule to the approximately 1,000 substances the worm already secretes, a molecule that is therapeutically beneficial to humans?” Mitreva remarked. “This study confirms that this is not merely a theoretical idea; it is achievable.”
Consider the potential for a worm that secretes extremely small amounts of food allergens to desensitize individuals to childhood food allergies.
Alex Loukas, director of the Australian Institute of Tropical Health and Medicine at James Cook University
Employing CRISPR gene-editing technology, the research team integrated a gene responsible for an antibody known to counteract the lethal pufferfish toxin tetrodotoxin into the hookworm’s genetic makeup at the egg stage. Mitreva’s group meticulously determined the gene’s insertion point, ensuring it did not disrupt essential DNA regions while still facilitating the production and secretion of the novel protein.
Subsequently, the team infected hamsters with 80 to 100 modified parasite larvae. Upon reaching maturity, the adult worms carrying the newly introduced gene successfully produced the antibody and released it into the hamster bloodstream. Blood samples collected from the infected hamsters subsequently demonstrated partial neutralization of tetrodotoxin in laboratory tests, indicating the worm-derived compounds were active within the host.
Hypothetically, the same methodology could be applied to secrete other antibodies or peptide medications—short protein chains—to directly address gastrointestinal ailments, Loukas noted.
“We are contemplating the active introduction of antibodies that inhibit inflammatory hormones or cytokines,” Loukas stated, to manage conditions such as inflammatory bowel disease. “One could also envision a worm that releases trace amounts of food allergens to desensitize the host, thereby addressing childhood food allergies,” he added.
Moving forward, the researchers aim to enhance the longevity of the therapeutic molecules secreted by the worms, given their limited production capacity, he pointed out.
Although infecting a person with a parasite to improve their health might seem counterintuitive, hookworms possess a remarkably safe biological profile, according to Loukas. A unique aspect of their biology prevents infections from escalating uncontrollably.
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Hookworm larvae penetrate the skin and travel to the small intestine, where they mature into adults, frequently residing for years without significant host impact. Any eggs produced by the adult parasites must hatch externally; they are expelled in the host’s feces. This biological mechanism ensures the population of adult worms within the body remains relatively stable.
Moreover, a single dose of standard anti-worm medication effectively eradicates the infection within 24 hours. Consequently, any hookworm-based therapies could be readily eliminated from an individual’s system.
“This is an exciting development that truly pioneers a novel approach to the delivery and generation of therapeutic molecules,” Loukas commented.
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