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Roche Achieves Sequencing on Semiconductor Platform; Automating ePCR with Japanese Partner

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Roche has made "significant progress" on the semiconductor sequencing technology it has been developing with DNA Electronics in the UK, showing internally that it can sequence DNA, In Sequence has learned.

In addition, the company has been working on a fully automated emulsion PCR device with Precision System Science, a long-term Japanese partner. That instrument, which will not be commercialized before the end of the year, is designed to streamline the workflow of Roche's 454 GS FLX+ and GS Junior platforms as well as the new semiconductor-based system.

According to Roche's Thomas Schinecker, the company's collaboration with DNA Electronics is "one of our main focuses on the R&D side" right now. Schinecker is president of Roche Sequencing Solutions, a unit that includes 454 and NimbleGen that Roche created last year as part of a restructuring of its Applied Science (IS 6/12/2012) business.

Schinecker said the partners, who have been collaborating since late 2010 (IS 11/2/2010), have shown internally that they can sequence DNA on their semiconductor chips, but he provided no timeline for commercializing the technology.

"As we move through the development process, we will work closely with early access customers to develop data that will be shared publically," he said.

The new platform will be a high-throughput sequencing system that will complement but not entirely replace the existing GS FLX+ and GS Junior platforms, which will still be used for smaller projects or those that require very long reads.

It will be based on DNA Electronics' ion-sensitive field-effect transistor, or ISFET, technology and will build on Roche's expertise in workflow design, sequencing informatics, and long read technology.

"We believe we can transfer the same expertise to our ISFET technology, so we can have long read lengths on our [new] system," Schinecker said, adding that Roche owns several patented algorithms "that will also help us with the ISFET technology."

He said that pricing will be one factor that will enable a new high-throughput sequencing system to be successful in the market, "but also important is to provide a complete workflow, which includes the bioinformatics solutions."

DNA Electronics owns intellectual property around chip-based DNA sequencing by hydrogen ion detection and other areas. Besides Roche, Ion Torrent has also taken a non-exclusive license to the company's IP (IS 8/3/2010).

Last November, Roche said it has been working under an exclusive agreement with Precision System Science of Japan to develop and manufacture a fully automated emulsion PCR instrument for its sequencing platforms.

The new device will reduce the required hands-on time from several hours to a few minutes. By taking out manual steps, it will also increase reproducibility, which Schinecker said is important for translational and clinical sequencing workflows.

Roche has been working on the instrument with PSS over the past year and has conducted feasibility studies on its sub-components, which include a technology for generating emulsions, a new thermocycler, and a new approach for emulsion breaking and enrichment.

"We have shown that we can maintain the long read lengths we achieve with the manual workflow also with the automated workflow," he said.

The company expects to provide a timeline for commercialization, as well as pricing information, toward the end of the year.

Roche has worked with PSS in the past on developing instrumentation for automated DNA extraction and has had "extremely good" experience with the firm, Schinecker said. "The systems that we've developed jointly with them have extremely high reliability."

Besides developing new sequencing and front-end systems, Roche will continue to improve its GS FLX+ and GS Junior platforms.

By April, Roche plans to launch software that will increase read length for amplicon sequencing on the GS FLX+. It already released similar software for shotgun sequencing on the FLX+ last fall, which has been well received by customers, Schinecker said, allowing them to achieve read lengths of up to 1,000 bases.

Next, Roche plans to bring the same extra-long read technology to the GS Junior, both for amplicon and for shotgun sequencing. Schinecker said the company's R&D organization is "actively working" on this and already has prototype upgraded instruments in its laboratory, which have the same outer shell as the current GS Junior. Roche plans to present additional information on a poster at the Advances in Genome Biology and Technology conference next month.

Furthermore, Roche's NimbleGen and 454, who have been conducting R&D under the same umbrella since the restructuring of Roche Applied Science, have been developing new sequence capture products, Schinecker said.

Last year, NimbleGen launched SeqCap EZ oncology and neurology panels and Roche plans to launch additional disease panels this year.

At the end of the year, it also plans to release a new generation of NimbleGen sequence capture technology that will significantly reduce turnaround time.

Overall, Roche's genomic analysis business – which includes revenue from 454 and NimbleGen – has been in decline over the last year, reporting a 21-percent decrease for the third quarter of 2012 (IS 10/16/2012). The company will report its fourth-quarter and full-year 2012 financial results on Jan. 30.

For new sequencing technology, besides its collaboration with DNA Electronics, Roche has a partnership with IBM for developing nanopore sequencing, as well as several projects with academic groups, such as Stuart Lindsay’s team at Arizona State University on nanopore readout technology.

A year ago, the company unsuccessfully tried to acquire Illumina, currently the market leader in next-generation sequencing.

More recently, Roche has been named as a potential bidder for Life Technologies and its Ion Torrent sequencing business, following news reports earlier this month that Life Tech is seeking a buyer (GWDN 1/18/2013).

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