VIDEO:
Scientists at the Biodesign Institute at Arizona State
University have received a 2-year, $5.3 million grant from the
Defense Advanced Research Projects Agency (DARPA) to protect
warfighters in the event of exposure to infectious diseases during
deployment.
Dr. Stephen Albert Johnston and his colleagues at the
Biodesign Institute have taken on a daunting test of skill: to
develop a potential therapeutic that can protect soldiers against
an unknown pathogen—and do it in a week.
Any commercially available therapeutic typically requires
about a decade or more to go from the benchtop to the marketplace.
“Half of this period involves all the research and development of
the therapeutic, the chemistry to make it, and so on,” said
Johnston, director of the Biodesign Institute’s Center for
Innovations in Medicine. “The other half is all the clinical trials
testing and FDA approval.” The group’s goal will focus on reducing
the front end of this process—the research and development
phase—to just 7 days.
The DARPA challenge was extended to the research community as
part of its Accelerated Critical Therapeutics program, a
long-standing initiative in response to emerging and novel
biological threats.
Johnston’s research team has developed new technologies that
could accomplish this seemingly impossible feat, drastically
reducing the time necessary to produce a general agent against a
disease-causing invader. In addition to benefiting the warfighter,
his team’s approach, involving the use of synthetic antibodies or
synbodies, may ultimately find its way into a broad range of
applications of benefit to the general public, including medical
diagnostics and vaccine development and validation.
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Like their human immune system counterparts, synbodies can
chemically sniff out invasive microbes with very high specificity,
binding with and neutralizing them. Synbodies against the selected
pathogen can then be rapidly produced and stockpiled using
high-throughput technologies. This assortment acts as a sort of
master tool kit, enabling researchers to rapidly construct a
custom-tailored therapeutic against virtually any
disease-associated protein.
The group has calculated that around 10,000 randomly
constructed synbody components, made from short protein fragments
called peptides, would provide sufficient variety to target
virtually any biological threat. For the DARPA test however, the
pool of synbodies can be dramatically reduced. “Our idea is to
screen a large library of possible pathogens, identifying a broad
class of effective binders, said assistant research professor Chris
Diehnelt. “We would then produce stocks of peptides to be kept
waiting in the wings, so that when we have a live fire test, the
unknown pathogen can be screened to identifying several low binding
affinity peptides. These we will rapidly assemble into a synbody,
targeting that pathogen specifically.”
The first test of their technology will come after the
group’s initial year of DARPA-funded research, at which time, the
group will be presented with a pathogen and required to generate an
effective therapeutic within 14 days. The second year goal of the
project aims to cut the production time in half. The team estimates
that an assortment of just 100 random peptide chains will be
sufficient to screen a broad range of pathogen threats, with the
certainty of finding multiple low-affinity chains, suitable for use
in synbodies.
Completion of the current project will open the door to a new
approach in the development of therapeutics to conquer one of the
major challenges to human health.
