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A Tour of Key Milestones in Synthetic Biology

August 25, 2021  |  Codex DNA

Synthetic biology has become so important and widely used that it’s easy to forget how young the field is. Much of the innovation that we rely on today took place in just the last two decades.

Codex DNA was originally formed as a subsidiary of Synthetic Genomics, Inc., in 2013 — but scientists from our team who helped found the company have contributed to some of the most important advances in synthetic biology since the field took off in the early 2000s.

Let’s take a quick look at some of the most influential.

First synthetic genome: Researchers synthesized the first complete genome of an organism in 2008. They used Mycoplasma genitalium, building and assembling a 582,970-base genome identical to the wild type genome except for one deleted gene and some added watermarks. This project showed that starting with small fragments and assembling them into larger and larger pieces was a feasible approach to building an entire synthetic genome. For this work, the team used synthetic oligos to create overlapping 5 kb to 7 kb pieces that were then stitched together into larger sections and cloned into E. coli and S. cerevisiae until the entire genome had been assembled correctly.

Gibson® assembly: In 2009, Dan Gibson (who later founded Codex DNA and now serves as our Chief Technology Officer) and his colleagues developed a revolutionary assembly technique that would eventually be known simply as “Gibson assembly.” This elegant method quickly replaced restriction enzyme cloning and enabled scientists to assemble synthetic DNA into molecules hundreds of kilobases long. Today, the method has been cited in more than 6,000 research papers.

First synthetic cell: By 2010, this team had built another a synthetic genome and raised the stakes by inserting it into a cell of a different species, essentially, booting it up to replicate the synthetic genome. The synthetic M. mycoides genome, the donor, was transplanted into a M. capricolum cell, the recipient. When that cell replicated under selection, new cells were found to carry the synthetic M. mycoides genome, with no M. capricolum DNA to be found.

First synthetic flu vaccine candidate: By the time an outbreak of the H7N9 bird flu occurred in 2013, Gibson and his team had already been working with collaborators at Novartis on a project to accelerate vaccine development. As concern mounted at the possibility of an imminent epidemic, Gibson and his collaborators adapted their vaccine work to the H7N9 flu situation. When the H7N9 viral genome was sequenced and published, Gibson and his colleagues used their synthetic biology skills to build the viral coat protein genes, HA and NA, which are used in flu vaccines. This took just two days; six days later, expression of the coat proteins was confirmed at Novartis. This was faster than it took the live virus to be shipped to the CDC. While that strain of flu did not become a global threat at that time, the vaccine candidate became part of the pandemic preparedness stockpile in the US.

First commercially available DNA printer: Gibson and a team of engineers eventually took the laborious manual processes needed to build long stretches of synthetic DNA and found ways to automate them into a contiguous workflow. That accomplishment became the basis for our BioXp™ system — the automated benchtop instrument for assembling and cloning synthetic genes — which was commercially launched in 2019. The system represents the combination of the molecular biology techniques developed by Gibson and his team for producing error-free DNA along with tremendous engineering and automation feats.

We’re proud that members of Codex DNA have been pioneering synthetic biology and developing techniques that have helped the entire field move forward. We are committed to continuing to innovate in this area and helping our customers achieve results and insights that would not have been otherwise possible.

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