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Prepping Beta Version of Nanopore Sequencer, Genia Touts Semiconductor Platform as Differentiator

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By Bernadette Toner

This article was originally published Jan. 16.

Genia, a Mountain View, Calif.-based startup, is looking to differentiate itself in the nanopore sequencing market by relying heavily on its management team's background in the semiconductor industry.

Stefan Roever, CEO and founder of the company, told In Sequence last week that the company has an alpha version of its single-molecule platform in hand and is currently optimizing the sequencing biochemistry for a beta system.

Roever declined to provide a commercialization timeline for the system or details regarding expected read length or accuracy, but noted that he believes the platform will be able to sequence genomes at a cost "one order of magnitude less" than other single-molecule systems, such as the Pacific Biosciences RS.

Describing the system as a "single-molecule electrical detection sequencing platform," Roever said the company expects it to be useful for targeted resequencing and molecular diagnostics that involve both human genomes and viral or bacterial DNA.

"A lot of the molecular diagnostics applications will profit greatly … from a single-molecule platform — less sample prep, cost, the ability to distribute because the machine will be smaller," Roever said.

The 15-person firm has been working quietly to develop its underlying platform since it was founded in 2009. Roever said the firm initially raised about half a million dollars from angel investors and then "did a big institutional round with a strategic investor" last April.

A company spokesperson said that the investor was Life Technologies, but the amount of its investment has not been disclosed. Life Tech declined to comment for this article.

Roever said the company currently has enough cash to develop "a working chip, plus the basics of the biochemistry," but plans to raise a Series B round in the range of "several tens of millions of dollars" in order to optimize the biochemistry for the system.

A Semiconductor-based Approach

The core of the company's management team — Roger Chen, CTO; Randy Davis, VP of R&D; and Pratima Rao, VP of marketing — came from analog semiconductor developer Maxim Integrated Products. After Chen left Maxim, he received an MS in biochemistry from the University of California, Santa Cruz, where he was a member of the Nanopore Project, an effort to develop ion channels for use in DNA sequencing. Roever, meantime, was co-founder and CEO of software firm Brokat Technologies before joining Genia.

Roever noted that the management team's semiconductor roots are the key to its sequencing approach.

"We took state-of-the-art semiconductor technology in these very sensitive analog-to-digital applications, where you're looking for very small currents and trying to convert that to digital signal, and we applied that technology to a biological problem," he said.

While a number of other firms are developing nanopore sequencing systems, including Oxford Nanopore, Nabsys, and NobleGen, Roever said that Genia's focus on the underlying chip platform sets it apart from competitors.

"We focused on operationalizing the nanopores," he said. "We essentially developed a way to create what are effectively lipid bilayer nanopore complexes, so the biological nanopore is a transmembrane protein that's suspended in a lipid bilayer." Genia is currently using an alpha-hemolysin pore and is exploring ways to genetically modify the pore to improve its performance.

The company has developed a way to "automatically set up whole arrays of [the nanopores] on the surface of a semiconductor chip and integrated circuit," ultimately making a "very complicated" process "massively scalable."

With the underlying platform in hand, "you can run any number of chemistries on that," Roever said.

Genia is developing its own chemistries to run on the chip, "but we would just as well happily make the chip available to other parties to run their own chemistries," he said. "Depending on the application there's going to be competing chemistries that could use this same underlying platform."

While the company claims that its platform-based approach to nanopore sequencing sets it apart from competitors, Oxford Nanopore is taking a very similar tack. ONP's GridIon system, which is still in development, is intended to serve as a flexible platform for a range of sensing applications, including the analysis of DNA, proteins, small molecules, and other analytes.

Furthermore, ONP holds a strong IP position around nanopore sequencing, owning or licensing more than 300 patents and patent applications that it claims cover "all aspects of nanopore sensing."

Roever did not comment on whether Genia has licensed any patents from Oxford Nanopore or other players in the field, but acknowledged that the intellectual property landscape around nanopore sequencing is "very fragmented," with different patents protecting "what pore you use, … how you control the movement of the DNA, how you go about collecting your signal."

He said that the company believes it has "freedom to operate in chemistries that will run on our chip," but is open to making the platform available for third-party chemistries.

The alpha version of Genia's chip has "a couple of hundred" pores, but the beta version will be "in the tens of thousands," Roever said.

"Ultimately, with the current architecture we think it can scale up to about a million," he added.

"One of the things to keep in mind is that these sensors are not one-time use, so you can run multiple molecules through every sensor," he said. "In the lab, for example, we've run up to 50,000 strands of DNA through a single nanopore."

He said that this is an advantage over other chip technologies, "where you have wells that get filled and get depleted."

With a million reusable sensors, he estimated that the Genia system would "easily get to throughput ranges that are comparable, if not exceeding, ... the desktop instruments today."

So far, the company has proof-of-concept that it can use its system to sequence DNA, "but we have not run any particularly long strands there," Roever said.

"We have a working platform and chip, and we have the basic building blocks on the biochemistry side. The next step is to take those and assemble them into a robust chemistry," he said. "That's where the focus is going to be and there's a significant amount of work still to be done there."

— Edward Winnick contributed reporting to this article.


Have topics you'd like to see covered in In Sequence? Contact the editor at jkarow [at] genomeweb [.] com.

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