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Darpa Seeking On-Demand, Distributed Production of Proteins

Aerial view of the Pentagon in Washington, D.C.

Pentagon in Washington, D.C., headquarters of the U.S. Department of Defense (

19 July 2023. A synthetic biology company is receiving a contract with the U.S. advanced defense research agency to devise a high-speed localized process for making therapeutic proteins. Ginkgo Bioworks in Boston is receiving an $18 million award from the Defense Advanced Research Projects Agency or Darpa for a four-year project to develop the process.

The project is part of a Darpa initiative called reimagining protein manufacturing. Darpa says producing proteins at scale for medical countermeasures and therapeutics today requires a massive centralized infrastructure, complex pipelines, and long lead times for cellular engineering. As a result, says the agency, several months are needed for production alone, with more time needed to get protein-based therapies into the hands of front-line clinicians.

Darpa’s R&D process seeks transformational change instead of incremental advances when confronting a problem, often by collaboration with industry and academic partners, and providing encouragement and resources to focus on novel solutions. In this case, Darpa is seeking a process to manufacture medical-grade proteins that can respond within 24 hours when provided with a DNA or RNA target template, produce fully active and validly designed complex proteins, and in sufficient quantities to achieve their medical countermeasure mission. In addition, the process needs to work in “denied, degraded, or disrupted operational environments” often encountered by U.S. armed forces.

Based on cell-free protein synthesis

For this initiative, Ginkgo Bioworks is leading a team with partners from synthetic biology labs at Imperial College London and the biotechnology company Nature’s Toolbox Inc. in Rio Rancho, New Mexico. The team is tasked with devising techniques that adapt cell-free protein synthesis. This process employs transcription and translation mechanisms of living cells, but accelerates that process by separating the protein synthesis machinery from cells. Those mechanisms are then harnessed to produce complex proteins on demand, meeting specified design and functional properties.

Ginkgo Bioworks says it’s applying its foundry technology with computational biology and automation for design of synthetic DNA and organisms meeting functional specifications. The company says its codebase, a library of cells, enzymes, and genetic codes, provides templates for a head-start on new protein design, including more than 2 billion genes in some 8 million natural product gene clusters for synthetic proteins.

Ginkgo Bioworks says it plans to adapt its work for Darpa to devise a process that also meets commercial pharmaceutical production standards called Good Manufacturing Practices to encourage adoption by the pharmaceutical industry. “There is growing recognition that pharmaceutical supply chains are at risk,” says Ginkgo Bio co-founder and CEO Jason Kelly in a company statement. “One way to meet this challenge is distributed manufacturing at the point of care,” adding, “Imagine a future where drugs, including complex biologics, are produced locally or in a widely distributed manner on-demand.”

In Apr. 2023, Science & Enterprise reported on a similar undertaking by Ginkgo Bioworks, a collaboration with companies in the U.K. and Slovakia to advance a process for reducing the cost and increasing the scale of messenger ribonucleic acid or mRNA manufacturing.  In synthetic forms, mRNA is used in vaccines and therapies to invoke specific immune responses, gaining recent popular recognition for Covid-19 vaccines.

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