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VisiGen to Offer 'Nano-Sequencing' Service by 2009

This article and has been updated to clarify the pricing of the company's sequencing service.
SALT LAKE CITY (GenomeWeb News) – Next-generation sequencing firm VisiGen Biotechnologies plans to offer a service based on its real-time single-molecule sequencing technology by the end of next year, CEO Susan Hardin said today.
Speaking at the Association for Biomolecular Research Facilities conference here, Hardin said that the company plans to launch a service based around its “nano-sequencing machine” technology by the end of 2009, and to follow that with the launch of equipment and reagents in another 18 months to two years.
Hardin said that the technology, which uses engineered DNA polymerase that acts as a “real-time sensor” for modified nucleotides, could eventually enable researchers to sequence an entire human genome in less than a day for under $1,000.
The company is currently working on its first version of the instrument, which can generate around 4 gigabases of data per day. At that throughput, she said the technology could sequence 44 human genomes per year at 10-fold coverage for around $1,000 per genome.
Hardin noted that while VisiGen's first commercial instrument is expected to enable whole-genome sequencing for $1,000, the company is not disclosing the projected costs for the sequencing service that it plans to introduce next year. She added that the firm will phase out the service once it launches the instrument because it does not want to compete with customers in the DNA sequencing service business.
The single-molecule approach requires no amplification, which eliminates a great deal of the cost relative to current sequencing technologies, she said.
In addition, read lengths for the instrument are expected to be around one kilobase, which is longer than any current next-gen sequencing platform. For example, the GS FLX system from Roche’s 454 Life Sciences subsidiary generates reads of around 250 base pairs, and the company expects to extend that to 400 bases in the next version of its platform. Illumina’s Genome Analyzer and Applied Biosystems’ SOLiD sequencers both have reads of around 30 base pairs.
ABI’s 3730 capillary electrophoresis system, by comparison, produces reads on the order of 700 to 800 base pairs. 
VisiGen is not the only next-generation sequencing firm looking to market a system with long read lengths, however. Last week, Pacific Biosciences said that it is currently seeing read lengths of around 1,500 bases for its system, which it plans to launch in 2010. The company claims that its technology will be able to generate 100 gigagbases of sequence per hour.
Hardin said that with improvements in the hardware, reagents, and software for the VisiGen system, its current throughput of one megabase per second could increase to 50 megabases per second.
VisiGen’s technology exploits polymerase’s natural biological role in synthesizing DNA. The company labels the enzyme with a donor fluorophore and attaches acceptor fluorophores to nucleotides so that whenever one of these nucleotides enters the active site of the polymerase, energy is transferred from donor to acceptor. In this process, called fluorescence resonance energy transfer, the acceptor gives off light of a particular wavelength that the instrument uses to identify the base.
Hardin said that the acceptor fluorophore is removed during nucleotide incorporation, which ensures that the DNA that results has no modifications that might slow down the polymerase.
Currently, she said, the company is working on refining its chemistry and detection technologies. In particular, she said, the team is working on slowing down the nucleotide incorporation step in order to detect a stronger fluorescence signal.
Hardin noted that the company also was awarded its first US Patent today, No. 7,329,492, “Methods for real-time single molecule sequence determination.”
Hardin founded VisiGen in 2000 along with Richard Willson, Xioalian Gao, David Tu, and Jim Briggs. The company has received undisclosed investments from Applied Biosystems and SeqWright, and also is supported by grants from the Defense Advanced Research Projects Agency, the National Human Genome Research Institute, and the National Institute of General Medical Sciences.
In 2006, VisiGen entered the Archon X Prize for Genomics competition, which is promising $10 million to the first team to sequence 100 human genomes in 10 days for no more than $10,000 per genome.

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