Humans have been using antibody therapies to treat infectious disease for more than 100 years. Blood plasma from influenza survivors administered to sick patients in 1912 may have contributed to their dramatic turnaround. In the years since, immune proteins from survivors have been administered to infected individuals in an attempt to combat diseases like Lassa fever, SARS, and even Ebola.
It’s hard, however, to find survivors who can donate plasma containing these lifesaving immune proteins. Now, a team led by researchers at the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) in Frederick, Maryland, has used genetically engineered cows to produce large amounts of human antibodies against hantavirus, an often deadly disease mainly transmitted from rodents to people. In animal models, at least, these antibodies provided robust protection against the virus, opening the door to therapies to treat and prevent hantavirus, for which there is no cure. The bioproduction technique also holds promise for generating antibodies against other infectious agents.
The work is preliminary and needs to be tested in people, but the team calls it a “proof-of-concept” that human antibodies can be grown in animals and retain their activity against disease. “I’m personally very excited about it. I think that this offers potential for treatment of patients with hantavirus infection,” says Greg Mertz, an infectious disease specialist at the University of New Mexico, Albuquerque, who was not involved in the research. “If you extrapolate this to other diseases, there are some where this approach might be promising.”
The USAMRIID researchers, led by virologist Jay Hooper, teamed up with SAB Biotherapeutics in Sioux Falls, South Dakota, to use genetically engineered cows that, when presented with an antigen, could produce fully human polyclonal antibodies against both the Sin Nombre hantavirus strain, first isolated from the Four Corners region of the southwestern United Sates, and the Andes hantavirus strain, which is prevalent in Chile. There, it infects an average of 55 people annually and kills about a third of them. After a lengthy incubation period and a few days of fever and muscle aches, the virus attacks the lungs and often causes acute respiratory failure leading to death. There is no cure, and the experimental vaccines would be logistically challenging to use even if they passed clinical trials.
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The "XNAzymes", as the researchers call them, could jump-start simple reactions, such as cutting and joining RNA strands in a test tube. One of the XNAzymes joined XNA strands together - something that represents one of the first steps to creating a living system, say scientists. Dr Holliger said: "Our work suggests that, in principle, there are a number of possible alternatives to nature's molecules that will support the catalytic processes required for life. Life's 'choice' of RNA and DNA may just be an accident of prehistoric chemistry." He said it was possible that life could be found on other planets, born from a molecular "backbone" other than DNA.
Back here on Earth, synthetic enzymes might be useful for treating human diseases such as cancer. Dr Holliger explained that XNAs are ideally suited as a therapy. Chemically, they are extremely hardy and, because they do not occur in nature, they can evade the body's natural degrading enzymes.
"This might make them an attractive candidate for long-lasting treatments that can disrupt disease-related RNAs," he said.
"And because we can modify chemistry at least to some extent to our hearts' content, we can make tailor-made enzymes for particular purposes." Prof Paul Freemont, an expert in structural biology at Imperial College London, said: "I can see how there could be therapeutic strategies downstream if we can start to mimic nature and develop synthetic variants. "What excites me more is the questions it raises about the origins of life. It provokes people to think that what we see on our planet is just one chemical possibility. It's the pure challenge of the chemistry of life."
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Having developed an expertise in the social side of science, the CEO of the Cooperative Research Centre Association, Professor Tony Peacock, is putting his skills to the test in building collaborations between researchers, industry and the community.
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