January 21, 2022
The recent increase in consumer demand for sustainably made products has led to a surge in the number of synthetic biology companies. From bio-based food to clothing to therapeutics, biomanufactured products are on the rise. One company contributing to the biomanufacturing boom is Sestina Bio. Sestina is designing a new platform for data-driven synthetic biology. With this powerful platform, Sestina is generating 100x the data of existing approaches.
“We created Sestina Bio to address the true complexity of engineering biology, specifically by generating much larger and more dimensional data sets to facilitate the learning phase of the Design-Build-Test-Learn cycle,” explained Bill Colston, founder and CEO of Sestina Bio.
A key part of Sestina’s unique approach involves a unique perspective on strain engineering. “At Sestina, we are...taking a minimalist approach to strain design. We believe that maintaining [evolutionary] fitness is paramount, that complexity is the enemy of robustness, and that the manufacturing maxim “start with the end in mind” begins with the strain,” said Andrew Horwitz, VP of R&D, Sestina Bio.
In line with this maxim, Sestina prioritizes evaluating a new strain’s performance in a simulated manufacturing environment: a stirred-tank bioreactor. To screen their new strains, the Sestina team had originally planned to use an industry-leading bioreactor system and allocated a budget of more than $1 million to purchase it for an in-house lab. Skeptical about using third-party services like CROs, Horwitz at first thought running their experiments in-house would be necessary to ensure high-quality, reproducible data.
When Horwitz first discovered Culture Biosciences, he saw clear benefits of using its cloud bioreactors for strain screening - increased efficiency, higher throughput, and shorter lead times - but was hesitant to outsource this vital work. “Having been in the industry for more than 10 years, I know the importance of generating reproducible data to assess strain performance and opportunities for strain improvements,” explained Horwitz. He planned to hold Sestina’s internal lab to the highest standards, running control strains against new strains, in triplicate, each week. The variability in the control strain each week would dictate the data quality of an entire run. “I wanted to work with Culture, but I didn’t know if Culture - or any third party lab - could meet our rigorous standards for data quality,” said Horwitz.
Given that it would take over a year to procure and install an in-house system, Horwitz decided to try out using Culture in the meantime through a technical transfer and scale-down validation project. During this initial phase of work, Sestina could stipulate experimental results that must be attained before beginning a Guaranteed Capacity subscription at Culture.
“I figured this initial project with Culture was a win-win for us. Either we’d meet our project objectives and we could start running experiments with Culture six months earlier than we would be able to internally, or we’d know quickly that Culture was not the right fit and we could proceed with setting up our own lab.”
In terms of the cost of working with Culture, Horwitz didn’t have to try hard to convince Sestina’s Chief Commercial Officer of the appeal. “Working with Culture instead of buying and running our own system is a no-brainer from a cost perspective,” said Peter Seufer-Wasserthal, Chief Commercial Officer, Sestina Bio.
“When we considered the cost of running such a system - including the amortized CAPEX of the equipment and the single-use consumables - we found that Culture costs about the same on an annual basis. However, with Culture, we don’t have to invest in a depreciating asset, pay overhead costs, and expand our team to manage a bioreactor lab.”
During a successful technical transfer and scale-down of Sestina’s process, Culture demonstrated its ability to meet Sestina’s exacting data reproducibility standards. Furthermore, Culture’s cloud bioreactors produced higher-quality data than many off-the-shelf systems. With newfound confidence that Culture could offer high-quality data and the bioreactor capacity to run as many replicates as needed, Sestina ultimately opted to partner with Culture through a Guaranteed Capacity subscription.
“What we’re trying to do at Sestina requires the highest level of operational excellence in fermentation screening, and building that capability in-house is a lengthy and expensive undertaking. Once we learned we could get high-quality data by running experiments at Culture instead of doing it ourselves - and we could monitor everything in real time - it made more sense for us to leverage Culture’s cloud bioreactors. Culture isn’t really a third party; it’s an integral extension of our team,” said Horwitz.
When it came time to hire a Director of Fermentation, partnering with Culture enabled Sestina to take an unconventional approach. With Culture taking on experiment execution, Sestina hired Mona Mirsiaghi as Director of Fermentation to focus on experiment design and analysis rather than focus on the typical tasks of hiring and managing a team of bioreactor operators. Beyond managing a team, a Director of Fermentation traditionally spends time (inevitably) compiling and reformatting data before even beginning analysis. Mirsiaghi instead uses Culture’s Cloud Console - a one-stop web app - to review and analyze data in real time, get insights quickly, and collaborate seamlessly with her colleagues.
Once they started running bioreactors at Culture, Sestina’s team found additional benefits of this model. “We soon realized that having access to more bioreactor capacity would be a huge advantage to us on an ongoing basis whether we already had an in-house system or not,” explained Mirsiaghi.
“Even if we built a lab internally, we’d only have 12 reactors and would have to reprioritize projects and push timelines if we were ever in a bind. With Culture’s guaranteed capacity model, we can reserve our bioreactors ahead of time in case of a surge in demand and scale up or down based on our needs. It’s a flexible model that is more conducive to the work of fermentation.”
“This mutually beneficial partnership is enabling us to make bioengineering a reality,” said Colston. “I’m excited for Sestina to continue growing alongside Culture as we help each other improve and innovate on our respective platforms. I’m confident that this collaboration will help unlock the potential of synthetic biology and scale it to create more sustainable products for the world.”
Modeling and simulation can be a powerful tool for bioprocess design. We now present InSiliCHO, an open source implementation for in silico simulation of Chinese hamster ovary cells (CHO) and a foundation for future work in DoE tools, active learning and more.
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