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Roche Broadens Sequencing Portfolio with Genia Acquisition; PacBio Partnership Continues

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NEW YORK (GenomeWeb) — Following its agreement with Pacific Biosciences last year to develop a sequencing platform for clinical diagnostics, Roche put its strategy for next-generation sequencing on a second leg this week by agreeing to acquire single-molecule nanopore sequencing startup Genia for up to $350 million.

Under the terms of the deal, expected to close soon, Roche will pay $125 million in cash and up to another $225 million tied to milestones.

Genia will become part of Roche's sequencing unit but will continue to operate as a standalone unit under the Genia name at its Mountain View, Calif., location. Its staff and management team, including CEO Stefan Roever, have been asked to stay on board.

Last month, Genia moved into a 20,000-square-foot facility that will allow it to grow to 80 to 90 employees, Roever told In Sequence. Its current team will be joined by Roche employees with expertise in operations and late-stage technology development and commercialization, according to Dan Zabrowski, head of Roche's sequencing unit.

Roche had been scanning the sequencing landscape for more than a year, he said. After visiting Genia in February, the two firms initially considered a strategic partnership but agreed on a merger instead.

Roche likes Genia's technology, he said, because it sequences single molecules, which avoids bias from clonal amplification; it reads one base at a time instead of several, reducing the informatics required and potentially boosting accuracy; and its chip-based detection platform is highly scalable, which could result in a fast and inexpensive sequencing system.

For Genia, Roche was a good fit because of the Swiss giant's commitment to sequencing in general, and its willingness to put "substantial resources" behind the development of the technology over the next few years, Roever said, significantly more than what Genia would have been able to contribute on its own. "We wanted to be with a partner where this technology would come to fruition and not just sit on the shelf somewhere," he said.

"With the acquisition of Genia, we believe that we now have the most differentiated next-generation sequencing portfolio for all of our customers segments," both in life science research and in the clinic, Zabrowski said.

But the company might not be done shopping for sequencing-related technologies yet. "Sequencing is a very fast-moving, evolving technology, and our people will continue to monitor that landscape, and if the opportunity exists to build on our portfolio, we'll do so," he said.

Besides developing sequencing platforms, Roche still has "work to do" in the areas of sample preparation and bioinformatics, he said, so it can offer a 'sample-in-report-out' type of system. "We will continue to make significant internal investments and also look for partnering opportunities to make that happen," he said.

Roche provided no timeline for commercializing Genia's technology and no details on what types of customers a Genia sequencer might serve. "The system is still in early development — we will have to overcome the usual type of challenges that any development project would have to," Zabrowski said.

Genia had originally planned to release a commercial sequencer for research use only by the end of this year, but Zabrowski indicated that this is rather unlikely. "I think Genia was well intended to deliver on that timeline, but what is a commercial product in one person's eye may not be a commercial product in someone else's eyes," he said.

Genia has been developing its nanopore sequencing technology since it was founded in 2009. The company employs protein nanopores in a lipid bilayer and has developed a semiconductor chip that fully integrates the analog-to-digital conversion of the signal, allowing the firm to scale to millions of sensors per chip, which Roever said sets it apart from other nanopore sequencing platforms.

Genia uses its nanopore platform as a detection system for a sequencing-by-synthesis NanoTag chemistry, which it exclusively licensed from academic partners at Columbia University and the National Institute of Standards and Technology. In brief, a polymerase tethered to a protein nanopore incorporates tagged nucleotides into a growing DNA strand. During that process, each tag enters the nanopore, where it is recorded as a change in ion current before being released.

Under a $5.25 million grant from the National Human Genome Research Institute, Genia has been working with academic collaborators, in particular Jingyue Ju's group at Columbia and George Church's lab at Harvard, to develop the chemistry further and plans to continue to do so. Roche will add its expertise in polymerase chemistry, Zabrowski said.

Roever said Genia and its partners "have shown proof of principle and have been able to gather sequence data," some of which they presented at the Advances in Genome Biology and Technology conference in February. "We've continued to make progress since then but haven't published any details," he said.

Genia's technology is somewhat akin to Oxford Nanopore's original nanopore sequencing approach, where a nanopore recorded nucleotides that were cleaved off by an exonuclease one by one. But the company abandoned that method about two years ago in favor of its current strand sequencing approach, where the DNA gets read as an intact strand that travels through the pore.

Some have suggested that because of these similarities, Genia might infringe on Oxford Nanopore's patent estate, but Roever said the company believes it has freedom to operate and that its technology is substantially different from what is protected under Oxford Nanopore's IP portfolio.

He said Genia's technology avoids many issues associated with strand sequencing, such as the signal coming from several bases rather than one, DNA secondary structure, and the need to slow down the DNA.

PacBio partnership intact

Roche's ongoing collaboration with Pacific Biosciences remains unaffected by the Genia acquisition. Under their agreement, announced last fall, the companies are developing a sequencing system for clinical diagnostics that is based on PacBio's single molecule sequencing technology. In conjunction with several clinical assays, the sequencer will be filed for marketing clearance with regulatory agencies in different countries.

Roche paid PacBio $35 million upfront and could pay up to $40 million more when certain development milestones are met. Roche will have exclusive distribution rights to the technology for diagnostics but not for research use.

According to Zabrowski, the partnership "is very healthy" and will continue following the Genia acquisition. Both the clinical PacBio sequencing platform and the Genia platform are at an early development stage, he said, so it is too early to provide timelines for either system.

Going forward, Roche plans "to assess the strength of both the Pacific Biosciences [clinical] platform as well as the Genia platform and then decide what are the most appropriate applications to be placed on each that would be best suited for our customers," he said.

According to PacBio CEO Mike Hunkapiller, the development program for the clinical sequencer is on track and his company expects to meet the first technology milestone later this year.

Should Roche decide to commercialize Genia's technology for diagnostic applications, Roche would lose its exclusive right to distribute PacBio's technology for diagnostics, allowing PacBio to sell it on its own or with another partner in that market.

However, Genia's technology "is still a research project," Hunkapiller said, and unlike PacBio's technology, which has been on the market for several years, no nanopore sequencing technology has been successfully commercialized yet. "I think it's a little premature to speculate what it might be used for in the diagnostic world, which tends to lag behind research use applications," he said.

In the research market, Genia might become a competitor for PacBio eventually, just as Roche's 454 GS FLX and GS Junior platforms, which Roche plans to phase out by 2016, are already competing with the PacBio RS II today. "When we set the agreement up, we were very careful to withhold any rights for them outside of clinical diagnostics because that's our core business," Hunkapiller said. "We knew at the time we did the deal that they were interested in a broader set of sequencing offerings for all markets, so we were not surprised" by the acquisition.

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