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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.
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 Chris Diehnel, assistant research professor. “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.
Written by Richard Harth
Biodesign Institute Science Writer