The Defense Advanced Research Projects Agency (DARPA), established in 1958, is an agency within the Department of Defense (DOD) responsible for catalyzing the development of technologies that maintain and advance the capabilities and technical superiority of the U.S. military. In short, it’s the way the U.S. military tries to prevent technical surprise.
The Nucleic acids On-demand Worldwide (NOW) program aims to develop a mobile medical countermeasure (MCM) manufacturing platform for use in stabilization and humanitarian operations to rapidly produce, formulate, and package hundreds of doses of nucleic acid therapeutics (DNA and/or RNA).
On-demand MCMs can better prepare deployed, field-forward forces against bio-threat attacks and emerging infectious disease. Fielding such a nucleic acid manufacturing platform will enable deployment of pure, sequence accurate MCMs in days, rather than months to years. And the mobile nature of the NOW platform will provide immediate threat response anywhere the military operates, mitigate surprise from disease threats, and ensure a resilient, readily accessible nucleic acid MCM manufacturing pipeline.
In April 2021, GE Research and a multi-disciplinary team that includes the Broad Institute, DNA Script, MEDInstill, Molecular Assemblies, and the University of Washington, was awarded a five-year, up to $41 million project through the DARPA’s NOW program. Such a rapidly scalable and deployable production process could dramatically increase the speed at which new vaccines, such as the recently approved COVID-19 vaccines, could be deployed.
The GE team, comprised of Dr. Nelson and his colleagues, Weston Griffin, Ph.D., Erik Kvam, Ph.D., and Brian Davis, Ph.D., represents a highly multi-disciplinary group with deep expertise in chemistry, molecular biology, cell biology, fluidic handling, engineering, automation, and quality control to simplify the production of DNA therapies. Together with their project partners, they bring all of the elements required to design this mobile manufacturing platform.
Until just recently, all the steps required to produce a DNA or RNA- based vaccine were manual, and significantly, required the use of bacterial cultures for bio-production of the DNA used. This use of bacterial cells then necessitates the use of multiple purification steps to eliminate impurities. DARPA recognized the unique and broad capabilities of this team not only to incorporate synthetic DNA production, but to automate and integrate all of the steps into a streamlined workflow to create this portable production system.
The novel synthetic method to produce industrial amounts of DNA, Dr. Nelson says, will be key towards enabling the new production system, stating, “Our team has experience and expertise using enzymes to make DNA synthetically instead of purifying it from living cells. This eliminates the requirement for bacterial cultures and the purification steps that entails. We believe that this reaction can be scaled easily in size and because it doesn’t use living cells that need to be fed and cared for and cleaned up after, can be automated.”
Dr. Nelson and the GE Research team is in the final stages of a project with the U.S. Department of Defense’s Defense Threat Reduction Agency (DTRA) to develop a faster method for making doses of DNA-based vaccines. Similar to the new DARPA project, the team’s research and technology is focused on the speed of amplifying or scaling the manufacture of a given vaccine. The new project with DARPA represents a significant opportunity to accelerate needed advancement to ready this new mobile vaccine production platform.
DNA Script announced on April 27, 2021 a partnership with Moderna, Inc. to develop a prototype for rapid mobile manufacturing of vaccines and therapeutics as part of the DARPA NOW Program. The partnership will employ DNA Script’s novel enzymatic synthesis platform to quickly generate high-fidelity nucleic acids without the use of hazardous chemical solvents to power Moderna’s existing manufacturing technology for the rapid production of messenger RNA therapeutics and vaccines. As part of the agreement, DNA Script will receive up to $5 million in grant funding from DARPA.
The resulting Good Manufacturing Practice (GMP-) quality nucleic acid (including mRNA) vaccines and therapeutics are intended to deliver near-instantaneous protections to both military personnel and local populations. The design envisions a manufacturing unit capable of producing hundreds of doses of medicines in a matter of days in a 6-foot x 6-foot x 6-foot (1.8m x 1.8m x 1.8m) container, deployable to remote locations around the world.
“We are thrilled to collaborate with Moderna and DARPA on this important initiative to create an innovative biotechnological approach to rapidly detect, characterize and mitigate threats from newly emerging or engineered pathogens,” said Thomas Ybert, Chief Executive Officer of DNA Script. “We believe that our fast, efficient and intuitive SYNTAX™️ nucleic acid printer, underpinned by our proprietary Enzymatic DNA Synthesis technology, has the potential to help prevent future pandemics. We’re proud to have been selected by both partners receiving awards under this DARPA NOW initiative.”
About DNA Script
Founded in 2014 in Paris, DNA Script is a disruptive DNA synthesis company engineering biology to accelerate breakthroughs in life science. The company is pioneering an alternative to traditional DNA synthesis called enzymatic DNA synthesis, or EDS, making this technology accessible to labs with the world’s first benchtop enzymatic synthesis instrument, SYNTAX™️.