A $10 million contract to develop novel medicines and diagnostics that can be used to thwart bioterrorism threats or an infectious disease epidemic has been awarded to SRI Biosciences by the SPAWAR Systems Center as part of the Defense Advanced Research Projects Agency’s (DARPA) Folded Non-Natural Polymers with Biological Functions program, known as Fold F(x).
The program aims to reimagine how proteins are constructed and to develop novel medicines and diagnostics as countermeasures to chemical and biological threats. The initial goal of the program is to develop biologically active non-natural polymers that are structurally similar to naturally occurring proteins, but without their limitations, such as sensitivity to heat denaturation or chemical degradation.
To develop the new polymers, SRI is combining its expertise inmedicinal chemistry and biopolymer design with a breakthrough approach to screening vast numbers of compounds.
As a proof of concept, the team will design, synthesize and screen chemically unique libraries of 100 million non-natural polymers for activity against a variety of agents, including toxins such as ricin and viruses such as the H1N1 bird flu strain of influenza, an SRI announcement explained, adding that, “By reimagining how proteins are constructed, SRI hopes to develop novel medicines and diagnostics as countermeasures to chemical and biological threats.
“The Fold Fx program will enable broad advances in miniaturization of biodefense countermeasures, with a goal to be robust enough for long term deployment in harsh environments where natural proteins do not survive,” Homeland Security Today was told by Nathan Collins, executive director of the Discovery Sciences Section in SRI Biosciences.
“Initially,” Collins said, “the development of these man made synthetic proteins will create advanced sensors, with greater sensitivity to warn both the war fighter and civilian populations of potential exposure to bio and chemical weapon terror threats.”
Continuing, Collins told Homeland Security Today that, “As a next generation these synthetic polymers are anticipated to not only detect such agents but also neutralism them. As the program expands we expect that synthetic proteins could be applied to healthcare development of diagnostics and therapeutics for the treatment of exposure to bioterror agents – creating an entirely new form of drugs for biodefense and treatment of human diseases. We anticipate plugging these types of molecules into our screening programs to identify new diagnostics and drugs. The drug approach would be entirely new and has a range of applications in therapy.”
“The novel polymers are being made from entirely new types of monomer structures based on drug-like scaffolds with high functional group density,” SRI said. “SRI’s compound screening innovation is based on its proprietary Fiber-Optic Array Scanning Technology (FASTcell). Originally developed to identify circulating tumor cells in a blood sample, FASTcell can distinguish a single tumor cell among tens of millions of healthy ones in a few minutes. With DARPA support, SRI is expanding this technology to screen 25 million compounds in just one minute.”
“Our goal is to develop a method that can enable rapid, large-scale responses to a bioterrorism threat or an infectious disease epidemic,” said Peter Madrid, Ph.D., program director in SRI Biosciences’ Center for Chemical Biology and co-principal investigator and leader of the chemistry effort of the project. “We are looking for non-natural polymers to detect or neutralize identified chemical or biological threats. Once we find potent molecules, we will be able to produce them at mass on a large scale.”
SRI said, “The overall goal of the Fold F(x) program is to expand on the utility of proteins and DNA, and to overcome their limitations by re-engineering their polymer backbones and side chain diversity—creating new molecules with improved functionality such as stability, potency and catalytic function in environments usually hostile for biopolymers. The knowledge to design new functional molecules from first principles doesn’t exist yet. The alternative is to synthesize enormous libraries of non-natural polymers and screen for sequences that have a desired action. Finding a single effective compound, such as one that can block a virus, may require screening hundreds of millions of compounds.”
“We are taking a full departure from how nature does things to come up with new ways of mimicking protein function in a highly tailored and controlled way,” said Collins, the principal investigator of SRI’s Fold F(x) project. “Our breakthrough has been to adapt SRI’s FASTcell technology to screen libraries of non-natural polymers. It’s very exciting to be doing such novel research.”
“Initially,” SRI’s announcement said, “the program will focus on screening massive numbers of non-natural polymers for potential uses against security threats. As a proof of concept, the team will design, synthesize and screen chemically unique libraries of 100 million non-natural polymers for activity against a variety of agents, including toxins such as ricin and viruses such as the H1N1 bird flu strain of influenza. As the program evolves it may progress to include a range of possibilities, such as how to synthesize molecules to fold such that they emit light, have enhanced levels of strength or elasticity, or store power.
