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SeqWell, Codexis Look to Optimize Enzyme Performance in NGS Workflows


BALTIMORE – With the mutual interest to expand their next-generation sequencing product portfolios, genomics company SeqWell and enzyme engineering company Codexis are working together to develop high-performance enzymes for NGS workflows, especially library preparation.

Through a collaboration announced last month, SeqWell aspires to pair its knowledge in high-throughput NGS library prep solutions with Codexis' expertise in enzyme discovery and optimization to expand SeqWell’s genomics workflow portfolio.

Although the companies have yet to disclose specific development projects, creating streamlined library prep workflows with multiplexing capabilities has been SeqWell's mission since its inception more than five years ago, said SeqWell Cofounder and CSO Joseph Mellor. The Beverly, Massachusetts-based firm was initially established to offer high-throughput NGS library prep services using its proprietary PlexWell technology, which later crystallized into a series of NGS library prep products, Mellor said.

"Many of our products — and frankly, many products in this space — rely on enzymes," said Mellor.

Specifically, Mellor said SeqWell's core technology, PlexWell, is based on transposase, and the company's products also rely on DNA polymerase for library amplification and reverse transcriptase for cDNA synthesis during transcriptome sequencing. While Mellor said SeqWell currently has its own proprietary enzymes, including the transposase, the company also designed part of the workflows to be compatible with off-the-shelf library amplification products.

Mellor noted that although SeqWell is still refining the scope of its collaboration with Codexis, he does not expect the partnership to be pinned on any one particular enzyme. Instead, he said the companies see a wide opportunity to enhance the performance of a broad class of enzymes that are implemented in NGS workflows, including coming up with novel enzymes for completely new products, he said.

What started as a business development opportunity sprouted into a serious partnership discussion last fall, resulting in Codexis leading SeqWell's Series C financing last month with a $5 million investment.

Given that enzymes are ubiquitous in NGS workflows, but many are not particularly optimized for their end-use applications, Codexis started to consider NGS as "a real sweet spot" for its enzyme engineering technology in the last few years, said Rob Wilson, senior VP and general manager of Codexis' performance enzymes business unit, who joins the SeqWell board as part of the partnership.

Codexis' proprietary enzyme optimization platform integrates high-throughput robotics and biochemistry assay modules, as well as deep data mining and interpretation algorithms, to enable highly efficient enzyme optimization, according to Wilson.

Wilson said Codexis will work closely with SeqWell scientists to identify desired enzyme properties for various applications. From there, Codexis will come up with high-throughput, miniaturized assays to help screen for and enhance those properties in the target enzymes.

Wilson also pointed out that the fundamental workflow of Codexis' enzyme engineering platform is fairly consistent regardless of the end-use application or the type of enzymes, which means the company can smoothly apply its platform technology to different enzymes throughout this collaboration.

In terms of potential intellectual property out of the collaboration, both Codexis and SeqWell said they are open to pursuing different potential IP models, including joint patents depending on the specifics of each collaborating effort. "The relationship with Codexis is extremely transparent and very positive," said Mellor.

Beyond the SeqWell collaboration, Codexis plans to continue growing its presence in the NGS space, Wilson said, adding that the company has been working with customers on several NGS-related products, including HiFi polymerase and reverse transcriptase which have been commercially launched in various markets in recent years.

In late 2019, Codexis announced a deal with Roche Sequencing Solutions under which it engineered and licensed an enzyme to Roche for its sequencing workflow, marking Codexis’ first public foray into the NGS space.

Moreover, Wilson said the company has a number of NGS-related customer research projects that will further expand Codexis' enzyme portfolio as these products gradually reach market over the next 12 to 18 months.

While Wilson said Codexis does not rule out the possibility of independently developing NGS products using its enzyme portfolio, the near-term goal for the company is still to help improve enzyme performance through collaborative efforts.

Meanwhile, SeqWell also has "some pretty ambitious plans," Mellor said. Given the company's aspirations to cater its products to high-throughput NGS applications, such as synthetic biology and cell and gene therapy, it will continue expanding its multiplexing sample prep workflow offerings.

To that initiative, in addition to the recent launch of its PurePlex DNA library prep kit, which combines the PlexWell technology with built-in dual indexing, the company also has some other "innovative concepts" for NGS library prep within its R&D pipeline, including one to be validated as early as the middle of this year, he said.

The company, which currently has approximately 40 employees, is also "growing quite quickly," Mellor said.

Although the standard SeqWell kits are primarily designed to produce Illumina sequencing libraries at this point, Mellor said the company has worked with partners in the past to evaluate and implement some of its workflows for other sequencers. The company's PlexWell workflow is also amendable to producing targeted amplicons, even though the technology is typically used to generate shotgun libraries.

Similarly, Mellor also said that the company is "very aware" of recent developments within the NGS industry, especially the addition of new sequencers and sequencing technologies, and is staying "flexible enough to respond to how the market develops."

"We want to make sure that we're hitting all of the different types of needs that customers might have," he added.