Infecting yourself with internal parasites doesn’t sound like the best way to feel better but scientists have “engineered” the genes of hookworms to deliver medicine – and “it’s just crazy enough to work”, said ZME Science.
US researchers have genetically modified hookworms to produce and secrete specific antibodies. This is a “first step” towards creating “living pharmaceutical factories” that can deliver therapeutic proteins “directly inside the host”, they said in their study, published in Nature Communications.
Internal leeches
The hookworm has “spent millions of years perfecting how to assure long-term survival inside a human host, and how to get molecules out of its body and into ours”, said senior author Makedonka Mitreva, from Washington University in St Louis, on EurekAlert.
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They are like an “internal leech”, infecting upwards of 400 million people globally, mostly in tropical regions, said LiveScience. As they latch on to the inner wall of the gut to feed on blood, they release “anti-inflammatory and immunosuppressant compounds to prevent the body from flushing them out”.
Scientists have already noted that this “cocktail of compounds” produced naturally by hookworms could help treat some metabolic disorders. But the new study takes things further – by engineering in an extra molecule for the worm to secrete.
Mitreva and her team used CRISPR gene-editing technology to insert into a hookworm egg genome “a gene coding for an antibody known to counteract” the pufferfish poison tetrodotoxin, a lethal, weaponisable neurotoxin with no known commercial antidote. They then infected hamsters with the modified parasites, and samples taken later showed the hamsters had antibodies to tetrodotoxin circulating in their blood.
“It was like the perfect moment,” Mitreva told R&D World. Now “we can start embarking on hookworms being a two-in-one platform” because we’ve shown they “can not only deliver a drug, but produce that drug and deliver it”.
‘Internal allies’
The goal now is to use this technology on humans. In the future, we “could see these worms engineered to produce a variety of other medications and excrete them inside the human body”, said LiveScience. They could potentially provide long-term treatments for chronic conditions such as inflammatory bowel disease, or even protective treatments for military personnel exposed to chemical or biological threats. Mitreva’s study was, in fact, funded by the US Department of Defense with a view to developing a treatment for tetrodotoxin poisoning.
This is an “exciting” approach that “paves the way for all sorts of injection-free biologic drug delivery”, said ZME Science. It’s “tantalising” to think that “engineered hookworms could one day” be our “internal allies, providing continuous therapeutic benefits while living safely within a human host”.
