Protective biosystems: parasites to fight against chemical and biological weapons

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Parasites could be part of the armor of military personnel and first responders to help them counter chemical and biological weapons attacks in war zones.

Charles River Analytics announced on September 14 that it had been awarded a contract from the Defense Advanced Research Projects Agency (DARPA) to lead a team of research organizations seeking to develop a new biosystem solution to protect fighters from chemical and biological threats. The five-year, $ 16 million contract will focus on neutralizing threats to vulnerable internal tissue barriers (including skin, airways and eye barriers) using a configurable biological countermeasure .

The effort is part of DARPA’s Personalized Protective Biosystem (PPB) program, which explores the use of novel transgenic commensal organisms – particularly hookworms and schistosomes – to secrete therapies specifically targeting chemical and biological threats, including neurotoxins (such as organophosphates) and microbial pathogens. .

“These organisms already live naturally in humans in areas where they are endemic. They have sophisticated secretory systems that can be manipulated to deliver immunotherapies to protect our women and men on the battlefield, ”said Dr. Bethany Bracken, senior scientist at Charles River Analytics and responsible for the effort. “Our goal is to insert a genetic sequence that provides the managed protection the human body needs to counter these biological threats.”

The effort includes a team of contractors including Baylor College of Medicine; George Washington University; James Cook University; Leiden University Medical Center; University of California, Irvine; and the Washington University School of Medicine in St. Louis.

Teams of Professor Alex Loukas and Dr Paul Giacomin of the Australian Institute of Tropical Health and Medicine at James Cook University will receive nearly US $ 2.5 million over five years to conduct research under this effort.

Molecular parasitologist Professor Loukas said the project aims to reduce the burden of personal protective equipment worn or carried by members of military and medical first responders in conflict areas to protect them from bioterrorism agents.

“What we are going to do at JCU builds on our work on parasitic helminth infections in human volunteers,” said Professor Loukas.

“By capitalizing on recent advances in genetic modification using CRISPR-Cas9, the team will create parasitic helminths that secrete drugs that thwart the agents of bioterrorism and thus protect the subject infected with the parasite from the agents. chemical and biological in a safe and well-tolerated manner. “

Professor Loukas said that as military technology and technology in general advance, these types of threats will become more common.

“It is clearly an advantage to have an internal biological solution to counter threats when they suddenly appear.

“We view parasitic helminths as internal molecular foundries, producing and distributing drugs throughout and throughout the body continuously, or on demand, if we wish,” said Prof Loukas.

George Washington University was awarded a $ 3.6 million contract to genetically modify commensal organisms to produce antidotes against harmful biological and chemical agents.

“We are genetically modifying the organisms responsible for the neglected tropical disease, schistosomiasis, to serve instead as a platform to deliver antibodies to frontline staff who are at risk of exposure to biological pathogens or harmful chemicals.” , Paul Brindley, PhD, professor of microbiology, immunology, and tropical medicine at GW School of Medicine and Health Sciences and principal investigator on the project at GW, said. “Our goal is to create an anti-threat solution that can be activated in 10 minutes or less and that can be quickly adapted to new threats. “

Brindley and his GW lab colleagues have expertise in using CRISPR / Cas9 to limit the impact of schistosomiasis and liver fluke infection. Since the agents that cause these diseases are able to enter and circulate in the human body, they also represent a potentially promising delivery vehicle for transporting antibody genes around the body. Brindley will use CRISPR / Cas9 to insert genetic information into the DNA of male organisms. As organisms move through their lives, the team aims to manipulate the segment of experimentally altered genetic material, or transgene, to perform programmed tasks, such as activating and deactivating and releasing an antibody. anti-pathogen in the body. Brindley and his research team will work with military labs to test real threats.

The first phase of the contract is for 24 months. If successful, additional funding will be received to move to phase two (also 24 months) and then phase three (12 months).

“We have some fascinating work ahead that could bring tremendous protective measures first to our fighters and eventually to the medical community at large,” said Rich Wronski, program director for the PPB effort and vice-versa. -President and Senior Scientist at Charles River Analytics. “Our team spans four countries and 14 time zones to include the world’s leading experts on hookworms and schistosomes.”


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