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The Next Generation in Sequencing Is SOLiD

By Kate McDonald Australian Life Scientist

July | August 2006 | Applied Biosystems (ABI) has completed the acquisition of Massachusetts-based genetic analysis company Agencourt Personal Genomics (APG) for $120 million and hopes to bring the company’s novel next-generation sequencing technology to market next year.

Impressively named the Supported Oligo Ligation Detection (SOLiD) process for massively parallel sequencing by stepwise ligation, the technology is an extremely high-throughput approach to DNA/RNA analysis. Applications include de novo genome sequencing, medical sequencing, gene expression, and high-throughput genotyping.

ABI president Catherine Burzik says: “After conducting a thorough evaluation of more than 40 companies and academic research groups, we have concluded that APG’s technology is both tested and commercial. We believe it should be able to address the scientific community’s goal of dramatically reducing the cost of sequencing without sacrificing quality.”

Competition to establish next-generation sequencing technology is heating up as companies such as Solexa challenge ABI’s two-decade dominance. Solexa recently began its first commercial shipments of its Genome Analysis System. “Solexa’s technology is bringing genome sequencing to a new stage of development,” says Eric Lander, director of the Broad Institute, which was one of the early-access beneficiaries. “Solexa’s system promises to address economically and rapidly a broad range of genetic analysis applications, and we are excited to capitalize on that potential.”

SOLiD Ground
ABI senior director for market development and strategic alliances, Andy Watson, said during a visit to Australia that the technology was capable of producing “two orders of magnitude more data than any other instrument on the market,” while dramatically reducing the cost. “That changes the way the science can be done. It lets new applications become feasible, and it simplifies a lot of the hands-on work.”

Watson said some aspects of the technology were novel, while others were improvements on regular fluorescence detectors with microscopes. “One of the novel aspects is the chemistry, the way the sequence gets read-out,” he said. “Other chemistries up until now have been based on extending the DNA base by base and reading them out. This chemistry allows every fifth base of the DNA to be read out and this is quite a novel approach.”

The APG technology combines single-tube microbead sample preparation with high-throughput multicolor fluorescence imaging. The sequencing uses ligation probes, an approach that the company said would provide very high-quality data compared to competitive polymerase-based approaches. APG’s process allows readings of millions of DNA fragments, unlike the Sanger method, which reads just one. This is the “massively parallel” part.

“The current electrophoresis technology will give you 96 samples in about 30 minutes, whereas this technology will give you a read-out of about a hundred million individual data points in the space of a few days,” Watson said. “That’s not to say that the electrophoresis technology is going to be replaced by this because there are other attributes that are not as good. The read length, for example, is much less with this.”

Watson pointed to cancer biology as one particularly promising application. “This technology is unique in its ability to start looking at what changes are happening in small numbers of cells in a large regular tumor. The health implication there is pretty significant in that the tumors are known to grow and metastasize based not on what the bulk of the tumor looks like but on how these little parts do.”

CE Not Forgotten
While ABI is excited about the potential of the Agencourt technology, it is not abandoning its mainstay — capillary electrophoresis (CE). ABI’s senior manager for genetic analysis systems, Carla Wike, says: “Capillary electrophoresis will be around for many years, and we’ll continue to add more applications. Our strategy is to simplify the workflow and expand the range of applications.”

Wike is currently developing an integrated sample preparation system, or black box, for the company’s CE systems and hopes to include up to five steps in the sample prep process within one box. Although still in its conceptual phase, the aim is to automate and miniaturize upfront sample preparation for CE. “It’s not going to be an expensive piece of equipment, and we expect to target labs that need automation but want to continue using existing CE equipment,” she says.

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