Removing Bottlenecks in Synthetic Biology with Cell-Free Synthesis of Long and Complex DNA

Companies to Watch – Elegen

In the first of four features on Elegen, Randy Dyer, vice president of marketing, talks about the spark behind the formation of the company as well as its mission to unlock the promise of synthetic biology by eliminating a critical bottleneck in the supply of synthetic DNA for genetic medicine development and other biotechnology applications. In the third feature join us for an in-depth discussion of Elegen’s cell-free DNA synthesis technology with Chief Scientific Officer Marc Unger.

by Marie Daghlian

To rapidly deliver on the promise of synthetic biology and the ability to program DNA for precise control of biology in biotech applications, the DNA manufacturing process needs innovation.

That’s how Matt Hill, who previously led the R&D team at diagnostics company Natera, sees it. Following his success at Natera, he founded Elegen in 2017 to solve the biggest bottleneck in the  “design-build-test-learn” cycle of DNA programming: building DNA.

Randy Dyer, VP of Marketing, Elegen

Innovating the Build Step

“To optimize a DNA sequence that serves as the program for cellular behavior, biologists use an iterative process that follows the engineering principle of design, build, test, and learn. The build step of that process is the slowest. Despite all of the innovation in the design, test, and learn stages of the cycle, many DNA build companies still rely on decades-old technologies and methods,” says Randy Dyer, vice president of marketing at Elegen.

That’s where Elegen comes in. The company delivers long, high-complexity, NGS-verified synthetic DNA at lengths up to 7kb to customers with a turnaround time of six to eight business days. The unparalleled combination of speed, length, accuracy, and complexity provides Elegen’s customers with a reliable supply of synthetic DNA to streamline their discovery and development processes.

The length and accuracy of Elegen’s ENFINIA™ DNA enable customers to eliminate the days or weeks required to assemble shorter pieces of DNA into longer, full-length constructs. “To get access to custom DNA in a reasonable amount of time, biologists often have to make compromises on sequence length, accuracy, and complexity,” says Dyer. “They typically order shorter DNA fragments that arrive fast but end up being of lower quality and then use conventional molecular biology methods to assemble those fragments into the longer DNA they need. Those short pieces have a high rate of error and require researchers to spend time cloning and sequencing the DNA before moving forward with experiments. The whole process is tedious, difficult to scale, and slow.”

Elegen’s proprietary cell-free DNA synthesis technology enables rapid and scalable production of DNA

DNA Without Compromise: Length, Complexity, Accuracy & Speed

To offer the market a faster option for long, accurate, and complex DNA, Elegen introduced ENFINIA DNA in March 2023 using their proprietary cell-free DNA synthesis technology. “We are the only company to produce long, complex, NGS-verified, linear DNA at lengths up to 7kb with a cell-free synthesis platform, and we’re delivering that DNA to customers as fast as six to eight business days,” Dyer says. Since ENFINIA DNA is shipped NGS-verified, Elegen’s customers can often use it directly in downstream workflows.

Elegen can manufacture DNA not only at the length and accuracy customers need but also with higher complexity than offered by other suppliers. The company just announced that it enhanced its synthesis process to enable the production of DNA with increased complexities, including those that are challenging for other suppliers to provide quickly, if at all.

“Our customers now have access to complex DNA that is very hard to manufacture, for example GC-rich promoters, enhancers, terminators, ITRs and LTRs, complex hairpins and long repeats, in a matter of days instead of waiting months as they may have for other suppliers, or simply shelving the design because it was too complex to build,” Dyer notes.

Benefits Upstream and Downstream

Dyer says the company’s customer base is growing rapidly and includes several top 10 biopharma companies. More recently, the greatest interest has come from companies looking to improve their process for developing genetic medicines.

“Speed is critically important in genetic medicine. In the discovery phase, when screening through a wide range of DNA designs, rapid access to long, accurate, and complex DNA allows researchers to explore a wider sequence space, faster,” says Dyer. “In this upstream phase, fast DNA delivered at the length, complexity, and accuracy needed for immediate use allows them to test more designs before selecting candidates for downstream clinical development.”

In the downstream phase, Elegen’s cell-free DNA synthesis can enable biopharma companies to bypass conventional cell-based cloning to accelerate the process of scaling DNA production. Traditionally, milligrams or grams of DNA have been produced using cell-based cloning, where engineered plasmid DNA is transfected into bacterial cells and replicated as bacterial colonies grow over time. The large mass of plasmid DNA is isolated from the bacteria, purified, and in some cases linearized before use in downstream processes.

Elegen’s cell-free DNA synthesis technology can easily scale to deliver linear DNA in larger quantities in less time. This is something Elegen is currently working to commercialize in the near future.  “Because cells aren’t used anywhere in the production of Elegen’s DNA, downstream purification and QC may also be simpler,” Dyer notes. “That’s a very attractive proposition for biopharma.”

From Technology Potential to Biopharma Partnerships

In January of this year, Elegen announced the signing of a collaboration and licensing agreement with GSK that uses Elegen’s cell-free DNA manufacturing platform in the development of GSK’s vaccines and medicines. The multi-year agreement provides Elegen with up to $35 million in near-term financial and development support as well as purchase commitments for their ENFINIA DNA. “The agreement signifies the potential for Elegen’s novel technology to accelerate genetic medicine development,” says Dyer, who expects to see more partnerships announced by Elegen in the future.


This is part 1 of the Big4Bio Company to Watch program for April 2024: Elegen
For more information on the series, click here.