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We Accidentally Built a Synthetic Cell Factory
We started b.next as a few academics looking to solve the problem of interoperability and integration in synthetic cell research, and help our community realize the potential of synthetic cells. Over the last few years, we've been hard at work on this with Nucleus. But that alone isn't enough: synthetic cells can only go so far without a dedicated physical supply chain. We took on the challenge and now operate a manufacturing plant building Cytosol—the core materials needed to build cells—made to Nucleus open specifications. We recently shipped our 100th kit. Building industrial-grade infrastructure wasn’t necessarily what we expected would be needed when we set out, but it's a critical next step for synthetic cells to grow from an academic effort to solving global-scale problems. This post shares that journey.
In 2023, we received a contract to build a simple synthetic cell sensor from fully open and specified components, as a means for jumpstarting collaborative and interoperable engineering of synthetic cells. A key part of our strategy was to build an open PURE system with easy-to-use protocols for construction, based on the OnePot PURE system. This was a clear need for the synthetic cell community, which had adopted the PURE system as its core platform, but practically only had access to non-extensible and non-modifiable commercial formulations. What we thought would take a few months turned into a multi-year undertaking as we uncovered foundational challenges in synthetic cell infrastructure and supply chains—and eventually led us to introduce and begin manufacturing “Cytosol” as a core substrate for building synthetic cells.
We were blocked at the very first step. We couldn’t acquire the 36 plasmids needed to implement the OnePot PURE system proteins. They were only available under restrictive material licensing terms (UBMTA), which as a company, we could not access—even though our goal was to make PURE better for the community. As we spoke with PURE researchers, we also learned that the available PURE plasmid set was incomplete and contained mutated plasmids. To our surprise, only a handful of labs around the world had actually successfully built the PURE system, often taking over 18 months to do so—a sobering length of time to get to a baseline technology first published in 2001.
We took this challenge head-on, re-designing and synthesizing our own improved, open-access set of PURE plasmids, and developing straightforward protocols for PURE protein production and assembly. After nine months of painstaking development, we could finally achieve detectable output—a critical milestone that confirmed that the open system could work at all. We shared our first set of PURE protocols and plasmids in mid-2024 through the Nucleus platform, which we had recently launched as an open commons for the community to build synthetic cells together.
But a functioning PURE system requires not just proteins—it also needs tRNA and ribosomes. When we started our work, tRNA were available from two providers: Roche and Sigma. In 2023, Roche stopped supplying tRNA. Then, just as we had gotten PURE proteins working with our open system, Sigma also stopped supplying tRNA. We learned that tRNA manufacturing had been deprioritized, and would be on back order indefinitely. A key reagent needed to build synthetic cells was suddenly unavailable.
We realized just how brittle the supply chains for synthetic cells were—a hodgepodge of different providers, often singular for a given reagent, none of whom cared about synthetic cell researchers in particular. As we began getting more requests for our open PURE DNA plasmid set, it became clear that achieving reliable synthetic cell engineering across the community would take more than we had originally planned for. The community needed reliable, open protocols not just for PURE proteins, but for every component.
By mid-2025, we had developed and optimized open protocols, specifications, and materials