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Roche and IBM to Co-Develop, Commercialize IBM's DNA Transistor Technology for Nanopore Sequencing

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By Monica Heger and Julia Karow

This article was originally published July 1.

Roche and IBM said last week that they will co-develop a nanopore sequencer based on IBM's DNA transistor technology. As part of the agreement, Roche will fund continued development of the technology at IBM and will provide additional resources through its 454 Life Sciences subsidiary. Roche will also receive an exclusive right to market products that are based on the technology.

With its bid in IBM's technology, Roche is aiming to stay ahead of the curve in the race to faster and cheaper sequencing, as its 454 technology appears to mature and as other vendors are developing their next generation of sequencing platforms.

Chris McLeod, president and CEO of 454, which is part of the Roche Applied Science business, told In Sequence that the company had been evaluating different single-molecule sequencing strategies — both nanopore and non-nanopore — and felt that IBM's approach was "the most promising." He said that IBM had also been looking for a partner to help bring its technology to market.

McLeod said IBM's DNA transistor technology "addresses one of the most fundamental problems with [nanopore] sequencing — controlling translocation speed." And, he added, the technology addresses it in a way that "still permits rapid sequencing, allows you to control the molecule, and gives you a highly accurate read."

McLeod said that the technology could be commercialized in about five years, but declined to give further specifics on the timeline, the details of the development process, or the financial arrangement with IBM.

Last year, the National Human Genome Research Institute, under its "$1,000 Genomes" grant program, awarded IBM $2.6 million over three years to develop an electrical device to control the translocation of DNA through a nanopore.

In November, researchers at IBM said that they had built the device and were in the process of optimizing it (IS 11/10/2009). McLeod confirmed that this was still true, and said that there were a number of technology development hurdles to overcome as well as hurdles associated with making the device user-friendly and ready to market.

At the Consumer Genetics conference in Boston last month, Ajay Royyuru, senior manager of the computational biology department at the IBM Watson Research Center, said that IBM researchers have successfully drilled a 2- to 3-nanometer-sized pore through layers of metal and insulator, pointing out that the pore "does not short out the electrodes."

"The device exists and functions in some manner," he said.

The researchers have also been able to record spikes from current changes when single DNA molecules — including 48-kilobase lambda-phage DNA — travel through the pore.

Simulations of DNA in the nanopore have also shown that its movement is not smooth but that it has a "stick-slip" motion, and the researchers believe that they "should be able to achieve some controllable movement."

They have also recently gotten "a pretty good handle" on another technical challenge, concerning electrochemistry on the electrodes, he said, and are currently "investigating approaches to testing translocation control."

Once they are able to stop the DNA in the pore, he said, they will look for ways to interrogate the bases.

The ultimate goal is to build a sequencer that will enable low-cost, rapid, and accurate sequencing of human genomes for clinical purposes, though 454's McLeod said it was premature to predict the speed or cost of the technology.

While a nanopore sequencer has yet to be commercialized, companies and research groups have shown an increasing interest in the field and have been pushing the technology forward.

Early last year, for example, Illumina invested $18 million in UK-based Oxford Nanopore Technologies, which is currently developing a sequencing technology that combines an exonuclease with a protein nanopore (IS 1/13/2010). Oxford Nanopore also licenses a large portfolio of nanopore-related intellectual property from the University of Oxford, Harvard University, and other institutions and has said in the past that it is considering solid-state nanopores and sequencing intact DNA strands for future generations of its technology.

Startup NobleGen Biosciences recently licensed technology developed by Amit Meller's group at Boston University that uses arrays of solid-state nanopores and optical detection (IS 5/25/2010).

Additionally, at the NHGRI's Advanced DNA Sequencing Technology Development meeting this spring, researchers from Nabsys, the University of Washington, and Meller's group all reported on significant advances in their respective approaches to nanopore sequencing (IS 3/16/2010).

McLeod acknowledged that IBM's nanopore sequencing technology was a long-term investment and said that the company will continue to look at other sequencing technologies that could potentially be brought to market sooner.

"We feel this is the most promising technology for true, real-time single-molecule sequencing. But, it is a risky technology, and we continue to evaluate others as they emerge," he said. "We're also committed to 454 technologies, as demonstrated by the recent launch of the GS Junior system."

A more near-term technology might help the company bridge the gap as its 454 platform is losing market share to Illumina's and Life Technologies' short-read instruments. Last year, for example, sales of 454's sequencing systems were flat (IS 4/20/2010), while both Illumina and Life Tech reported strong growth in next-gen sequencing platform sales.

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