Protective Biosystems: Parasites to Fight Chemical and Biological Weapons
Parasites could become part of the armour of military personnel and first responders to help them counter chemical and biological weapon attacks in war zones.
Charles River Analytics announced Sep. 14 it was awarded a contract by the Defense Advanced Research Projects Agency (DARPA) to lead a team of research organizations seeking to develop a novel biosystem solution to protect warfighters from chemical and biological threats. The five-year, $16M contract will focus on neutralizing threats at vulnerable internal tissue barriers (including skin, airway, and ocular barriers) using a configurable biological countermeasure.
The effort is part of DARPA’s Personalized Protective Biosystem (PPB) program, which is exploring the use of new transgenic commensal organisms—specifically hookworms and schistosomes—to secrete therapeutics 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 provide immunotherapies to protect our women and men on the battlefield,” said Dr. Bethany Bracken, Principal Scientist at Charles River Analytics and lead of the effort. “Our goal is to insert a genetic sequence that provides the managed protection that the human body needs to counter these biological threats.”
The effort includes a team of subcontractors including Baylor College of Medicine; George Washington University; James Cook University; Leiden University Medical Center; University of California, Irvine; and Washington University School of Medicine in St. Louis.
Professor Alex Loukas’ and Dr. Paul Giacomin’s teams from James Cook University’s Australian Institute of Tropical Health and Medicine will receive nearly US $2.5 million over five years to conduct research as part of the effort.
Professor Loukas, a molecular parasitologist, said the project is intended to reduce the burden of personal protective equipment worn or carried by members of the military and medical first responders in conflict zones to protect them against bioterrorism agents.
“What we will be doing at JCU builds on our work with parasitic helminth infections in human volunteers,” said Professor Loukas.
“Capitalising on recent advances in genetic modification using CRISPR-Cas9, the team will create parasitic helminths that secrete drugs that counteract bioterrorism agents, and thereby protect the parasite-infected subject against chemical and biological agents in a safe and well tolerated manner.”
Professor Loukas said as military technology and technology in general advances, these kinds 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 are thinking of parasitic helminths as internal molecular foundries, producing and delivering drugs within and throughout the body continuously, or on demand, if we so choose,” said Professor Loukas.
The George Washington University has been awarded a $3.6 million contract to genetically modify commensal organisms to produce antidotes for harmful biological and chemical agents.
“We are genetically modifying the organisms responsible for the neglected tropical disease, schistosomiasis, to instead serve as a platform for delivering antibodies to frontline personnel who risk exposure to biological pathogens or harmful chemicals,” Paul Brindley, PhD, professor of microbiology, immunology, and tropical medicine at the GW School of Medicine and Health Sciences and lead 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 can be quickly adapted for new threats.”
Brindley and his lab colleagues at GW have expertise in using CRISPR/Cas9 to limit the impact of schistosomiasis and liver fluke infection. Because the agents that cause these diseases are adept at entering and circulating in the human body, they represent a potentially promising delivery vehicle for carrying antibody genes into the body as well. Brindley will use CRISPR/Cas9 to plug genetic information into the DNA of male organisms. As the organisms cycle through their life, the team aims to manipulate the experimentally gene-edited segment of genetic material, or transgene, to perform programmed tasks, such as turning on and off and releasing an anti-pathogen antibody into the body. Brindley and his research team will work in concert with military labs to test against real threats.
The first phase of the contract is 24 months. If successful, additional funding will be received to progress to phase two (also 24 months) and then phase three (12 months).
“We have fascinating work ahead, which could bring tremendous protective measures first to our warfighters and eventually to the medical community overall,” said Rich Wronski, Program Manager for the PPB effort and Vice President and Principal Scientist at Charles River Analytics. “Our team spans four countries and 14 time zones to include the world’s foremost experts on hookworms and schistosomes.”