The Defense Advanced Research Projects Agency (DARPA) has announced that Ginkgo Bioworks, which is building a platform for cell programming and biosecurity, has been awarded a four-year contract worth up to $18 million to reimagine how to manufacture complex therapeutic proteins.
As a performer on DARPA’s Reimagining Protein Manufacturing (RPM) project, Ginkgo aims to deliver advances in on-demand protein manufacturing by leveraging Cell-Free Protein Synthesis (CFPS) to enable rapid, high-yield, distributed production of human therapeutic proteins that support national security objectives. Ginkgo will lead a team comprising representatives from Imperial College London, led by Professor Paul Freemont, Nature’s Toolbox, led by Alex Koglin, and consultant Michael Feldhaus (former Executive VP of Antibody Discovery at Adimab).
Therapeutic proteins bearing so-called ‘post-translational modifications’, such as antibodies, cytokines, and clotting factors, are particularly important in the marketplace and to DARPA, as are subunit and conjugate vaccines.
Half of the top-selling drugs used to treat cancer and autoimmune diseases are such therapeutic proteins; many are also used as medical countermeasures to treat or prevent disease, injury, or death related to chemical, biological, radiological, or nuclear threats.
Through this programme, Ginkgo hopes to transform how therapeutic proteins are made, replacing cell-based methods with cell-free methods. Traditional centralised, large-scale manufacturing methods have usually sufficed, but increasingly there are use cases where rapid distributed or on-demand manufacturing is needed, such as supplying of therapeutic proteins to geographically isolated locales, providing hospitals and clinics with point-of-need rapid production of medicines from common precursors, and improving our ability to mount rapid and targeted responses to natural or man-made biological threats and emergencies.
Traditional production methods rely on weeks- to months-long construction of bespoke cellular organisms that have been engineered to produce the desired therapeutic protein during days-long fermentation processes. Even with standardised methods, it typically takes months to achieve the first useful production of a biological drug. Post-expression isolation and purification are equally challenging: each unique process is costly and time-consuming to develop.
Cell-Free Protein Synthesis (CFPS)
CFPS, by contrast, brings the key advantages of greater speed and flexibility than cell- and fermentation-based production. Significant improvements are needed to make CFPS competitive with traditional therapeutic protein production, however, primarily with respect to efficiency and the identity and homogeneity of post-translational modifications. In this programme, Ginkgo seeks to address these challenges and hopes to enable the rapid prototyping of enzymes and other proteins for diverse therapeutic and nontherapeutic projects. One aim of the project is to create production methods that are compatible with Good Manufacturing Practices, thereby facilitating adoption by the pharmaceutical industry.
Ginkgo will leverage innovative technologies enabled by its high-throughput, automated Foundry and its proprietary genetic data Codebase, a portfolio of reusable biological assets which includes more than one billion proprietary gene sequences. Ginkgo’s synthetic biology platform, coupled with its extensive expertise in iterative Design–Build–Test–Learn-driven biological engineering, enables the rapid prototyping, optimisation, and development of proteins, enzymes, metabolic pathways, and whole organisms under commercial-scale manufacturing conditions processes.