454 and Solexa Pursued by Pack of Next-Gen Sequencing Shops; Competition to Heat up in 2006

NEW YORK, Dec. 19 (GenomeWeb News) - Last Monday, Solexa launched its DNA sequencing, expression profiling, and microRNA analysis platform, the Solexa Genome Analysis System, following the lead of 454 Life Sciences, which introduced its Genome Sequencer 20 earlier this year. But while these two firms were the first to bring their next-generation sequencing technologies to market, they have plenty of competitors nipping at their heels -- with some shops scheduled to release components of their systems as early as next year.

Microchip Biotechnologies, located in Fremont, Calif., is developing a system that it calls the NanoBioSequencer. Stevan Jovanovich told GenomeWeb News that the company expects to commercialize an integrated system with sample preparation and separations in 2008, but it should have other news sooner. "We are building modular instrumentation and expect to release it in stages," Jovanovich said. "We anticipate launching a sample-preparation instrument in 2006."

The heart of the upcoming sequencing system is a microchip-based device that can label and process DNA fragments from individual microbeads in low-volume reactions, followed by ultra-fast separation and analysis on microfabricated capillary electrophoresis channels. The company is striving for long paired reads. "The goal is 800 bases," said Jovanovich.

AQI Sciences is also working feverishly on its platform, which is based on a novel single-molecule sequencing method. "We are still working very hard on this in Tucson, Ariz., leasing lab space from the Universityof Arizona," said Michael Andregg, who co-founded the company with his brother in April 2003. "We are still in the experimental stages. As of today we have not demonstrated proof of principle, but are very close. There are four main parts to our proposed technology, and we have demonstrated the first three."

Andregg declined to discuss the technology in much detail for competitive reasons. "The technique we are pursuing is a novel one, that to our knowledge, no one else is working on. It has the main advantage of [megabase] read length," he said. The company's private seed capital is running low, and Andregg said he is on the lookout for interested investors. He estimates the method would cost "around $500 to $1,000 per genome, per day, per device, within six months of proof of principle with sufficient funding." Proof of principle could be as early as six months away, according to Andregg.

Li-Cor Biosciences, meanwhile, is developing a technology to detect the release of reaction products when nucleotides are incorporated into single DNA strands. "We are on the brink of being able to demonstrate if it is going to work. We'll have a thumb's up/thumb's down on it within a few months," said John Williams, principal scientist with the company. The company has its patents in order. "We own patents on phosphate-labeled nucleotides and there are a few other groups that have filed, so we'll see what happens there," said Williams.

Williams said the company is focused on achieving long read sequences, on the order of tens of thousands of kilobases. "That is what really distinguishes what we and our close competitors are trying to do, as compared to 454 or Solexa or Agencourt -- really long read lengths," he said.

Agilent Laboratories is also aiming toward long read lengths, but with nanopore technology. The company wants to stream single strands of DNA sequentially through a nanopore hole, while an immobile detector reads out the bases. According to Mary Lou Simmermacher, technology communications manager at Agilent, the company hasn't yet achieved single-nucleotide resolution and any commercial instrument is expected to be several years out.

A number of other companies also indicated that their instruments are not expected on the market in 2006. Petra van Husen, a spokesperson for Germany-based Genovoxx, said the company's massively parallel single-molecule sequencing technology is still in the R&D stage. The technology is based on the company's patented Any Gene method, and Van Husen estimated the technology would be ready in one to three years. VisiGen Biotechnologies, which is developing a single-molecule technology, is also in the early stages of research, while officials from Pacific Biosciences, formerly Nanofluidics, declined to divulge where the company is with its research.

Two companies that appear to be much farther along with their technology are Helicos Biosciences and Agencourt Bioscience.

Agencourt's  highly parallel sequencing approach involves synthesizing short regions of identical DNA fragments on magnetic beads, packaging millions of them into a chamber, and then extending each of those molecules while detecting the addition of fluorescently labeled nucleotides. In August, Agencourt published proof of principle by resequencing Escherichia coli, but the company did not return calls inquiring about further progress.

Helicos has indicated that it expects to have its instrument in beta testing by next year and a commercial system available in 2007. The company's technology relies on cyclic sequencing by synthesis, by placing 1.2 billion strands of DNA on a substrate, adding a terminal transferase, priming each strand, and interrogating the mix with red and green lasers. Today, Helicos announced that it has successfully sequenced the M13 genome, by utilizing its non-amplified True Single Molecule Sequencing technology in conjunction with its SimplePrep genome preparation technique. But this is not all the news we can expect from the company.

Helicos CEO Stanley Lapidus told GenomeWeb News last week that he would soon be announcing the firm's "first early-access collaboration." It's possible this could be with the Institute for Systems Biology. At the 12^th European Congress on Biotechnology held in August, Lee Hood, president of ISB, said the institute was considering testing one of the Helicos instruments.