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Meet the BioXp™ 3250 system, our new automated synthetic biology workstation

August 26, 2020 | Codex DNA

Please join us in welcoming the newest member of the Codex DNA family. Like its BioXp™ 3200 predecessor, the BioXp™ 3250 system is a fully automated, benchtop platform for synthetic biology workflows — but this one reduces the timelines for identifying vaccine and antibody candidates from weeks to days by automatically assembling DNA clones, libraries, and gene fragments of up to 7,000 base pairs, in a single overnight run. Our users now have greater flexibility to generate full-length genes or long DNA constructs at unprecedented rates, reducing iteration cycle times.

As we celebrate the launch of this new system, we’ve been having not-so-distant memories of a time when all this work had to be conducted manually at the bench. It was our scientific team, led by Codex DNA co-founder and CTO Dan Gibson, who realized that the protocols had become so routine they should be amenable to automation. Our scientists were then working hard on flu vaccine development programs, building synthetic genes to short-circuit the tedious traditional process of relying on chicken eggs.

“We had a very ambitious goal to go from DNA sequence to the start of vaccine production in just five days,” Gibson recalls of those early days. “We wanted the DNA synthesis part of that workflow to take less than 24 hours.”

That big idea led to incredible scientific and engineering efforts required to create the first BioXp™ system. Our team designed a robust, automation-friendly process to mimic the manual techniques for assembling short oligos, transfecting them in E. coli, and reassembling them to build a whole gene. They also developed an enzyme-driven error-correction process to dramatically improve the fidelity of the DNA constructs generated.

We had that original prototype in mind as we engineered the new BioXp™ 3250 system, which is backward compatible with consumables for the BioXp™ 3200 system. We added multi-fragment capabilities so users can now clone up to four fragments at a time in the same vector. We’ve also expanded the choice of vectors and made it easier for users to incorporate their own custom vectors. Accuracy, reliability, and quality have been improved. There’s a streamlined user interface. And the system also meets strict ISO requirements for customers who operate in very rigorous or GMP-compliant environments.

The goal for the BioXp™ 3250 system was clear from the start: expand upon the success of our original platform by giving users more flexibility, more capacity, and more applications. With longer fragment sizes and multi-fragment function, our customers can go well beyond the original system’s limit of 1.8 kb to make full-length genes — even whole mammalian genes — in a single run. With fewer assembly steps, the new system will accelerate synthetic biology workflows for the discovery of candidate drugs for infectious disease and cancer and for answering gene function questions.

A great example of how the new system will make a difference comes from vaccine development in the COVID-19 pandemic. By automatically assembling error-free viral genes in a single overnight run, the BioXp™ 3250 system shortens timelines for identifying vaccine candidates from weeks and months to days. Typically, the next step is generating high-diversity scanning and combinatorial DNA libraries to optimize genomic function by rapidly iterating and elucidating the individual genes across the entire genome. Now, these processes are automatically handled by the BioXp™ 3250 system in its overnight run as well. The platform also has broad utility for any biological drug discovery or personalized medicine application, including clinical applications like neoantigen and TCR therapy.

In addition to making this new system available for customers to use in their labs, we will also be launching an in-house genomic DNA assembly and DNA library services business. With two technicians operating a dozen BioXp™ systems, our genomic output approaches one million base pairs, daily.

In our statement announcing this new system, our co-founder and CEO Todd Nelson said, “The BioXp™ 3250 application modules provide a complete suite of synthetic biology applications, enabling quick iteration of DNA libraries, large genomic DNA assemblies, automated cloning, and amplification. In short, we can optimize vaccine and biological drug development faster than anyone on the planet.”

Excited as we are about the BioXp™ 3250 system, we won’t be resting on our laurels. The Codex DNA mission is to democratize synthetic biology, and there is much more to do on that front. Our ultimate goal is to build what we’re calling the DBC or digital-to-biological converter. This approach would begin not with oligos, which can take days to procure, but with sequence data. The instrument we envision would take data and produce synthetic genes, or even convert those automatically into needed RNA or proteins. This would enable what Gibson calls a “sequence-in, vaccines-out” concept that could replace the months-long manufacturing processes required today with something that could be done in a day or two.

We know, that sounds a little pie-in-the-sky. But it wasn’t too long ago that an automated synthetic biology workstation seemed impossible too.

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