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VisiGen Targets Megabase-Per-Second Sequencer

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VisiGen Biotechnologies has great ambitions: The company is not only targeting the $1,000 genome, but the $1,000 genome in less than a day.

The Houston-based company, which received an undisclosed equity investment from Applied Biosystems in late 2005, was founded in 2000 to develop a real-time single-molecule sequencing-by-synthesis technology that will eventually read 1 million bases of DNA per second. It hopes to offer a sequencing service based on its technology by the end of 2009, followed by an instrument release about two years after that.

“With that kind of throughput, you can get 10X coverage of a human genome in way less than a day,” says Susan Hardin, VisiGen’s founder, president, and CEO.

VisiGen’s approach relies on monitoring DNA polymerase, which the company calls a “nano-sequencing machine,” as it synthesizes DNA. The polymerase is labeled with a donor fluorophore and incorporates nucleotides labeled with acceptor fluorophores into a DNA strand. Whenever a nucleotide binds to the active site of the enzyme, energy is transferred from donor to acceptor in a process called fluorescence resonance energy transfer, or FRET. The acceptor gives off light of a particular wavelength that is detected and identified by VisiGen’s system.

By tracking many polymerase molecules in parallel as they synthesize DNA, VisiGen hopes to achieve a throughput of a million bases per second. Read lengths will reach about 1,000 base pairs, limited by how long the polymerase stays on the DNA, and how long the polymerase label will stay intact.

The system is able to track each polymerase in real time because the enzyme completely removes the acceptor label before it binds to the next nucleotide. Removing the label, which is attached to the last, or gamma, phosphate of the nucleotide, also results in “absolutely natural DNA” with no modification that could slow down the polymerase, Hardin says.

Julia Karow

Short Reads

The X Prize Foundation announced that Reveo has thrown its hat in the ring for the genome-sequencing competition. Reveo will use a sequencing tool called the Omni Molecular Recognizer Application, which is based on semiconductor electronics and photonics. Other competitors vying for the prize include VisiGen Biotechnologies, Roche’s 454 Life Sciences, and the Foundation for Applied Molecular Evolution.

In announcing its first-quarter revenues, Illumina said that the Genetic Analyzer instrument contributed significantly to its growth, though it did not break out specific numbers for the sequencers. The company’s total instrument revenue for the first quarter more than tripled to $19.6 million from $5.9 million.

The Joint Genome Institute will conduct a pilot project — sequencing 100 culturable microbes — that could help lead to a large-scale international project to sequence thousands of cultured microbes. The goal is to increase the diversity of sequenced genomes for bacteria and archaea.

In a reexamination requested by a Florida law firm, the US Patent and Trademark Office preliminarily rejected all claims in two patents licensed by Solexa relating to 3’-protected reversible terminator chemistry. The law firm declined to disclose the client on whose behalf it was acting. The prior-art ruling could still be reversed.

Patents

US Patent 7,211,414. Enzymatic nucleic acid synthesis: compositions and methods for altering monomer incorporation fidelity. Inventors: Susan Hardin, Xiaolian Gao, James Briggs, Richard Willson, and Shiao-Chun Tu. Assignee: VisiGen Biotechnologies. Issued: May 1, 2007.

According to the abstract, “Nucleotide triphosphate probes containing a molecular and/or atomic tag … are disclosed, and kits and method for using the tagged nucleotides in sequencing reactions and various assay.”

US Patent 7,211,390. Method of sequencing a nucleic acid. Inventors: Jonathan Rothberg, Joel Bader, Scott Dewell, Keith McDade, John Simpson, Jan Berka, and Christopher Colangelo. Assignee: 454 Life Sciences. Issued: May 1, 2007.

This patent covers methods and devices for nucleic acid sequencing, including a method that involves “annealing a population of circular nucleic acid molecules to a plurality of anchor primers linked to a solid support, and amplifying those members of the population of circular nucleic acid molecules which anneal to the target nucleic acid, and then sequencing the amplified molecules by detecting the presence of a sequence byproduct such as pyrophosphate.”

Data Point

3%

Rate of growth for Applied Biosystems’ capillary electrophoresis sequencing business in the first quarter of 2007 compared to the same period the year before. ABI says revenue from DNA sequencing-related products was $140.7 million.

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