Company Profile:

454 Life Sciences Corporation has developed and is commercializing advanced proprietary technologies for sequencing DNA. The Company, headquartered in Branford, CT, provides a substantially faster, cheaper, simpler and more comprehensive solution for sequencing DNA. When compared with the prevalent sequencing technology, known as Sanger sequencing, the current version of 454 Sequencing™ allows 454’s customers to achieve 60 times greater throughput when sequencing DNA at a significantly reduced cost that also avoids the significant infrastructure and capital investment required by Sanger sequencing to effect high-throughput and reasonable sample preparation time. The combination of increased throughput, shortened sample preparation and overall ease of use of the system reduces the time to sequence a typical bacteria from a month with conventional sequencing to three days with the 454 Sequencing System.

454 Sequencing is commercially available at the 454 Sequencing Center, which offers sequencing services to clients world-wide whereby samples are sent to and sequenced by 454 Life Sciences, and from Roche Diagnostics, the exclusive world-wide distributor of the Genome Sequencer 20â„¢ System and reagents. 454 Life Sciences is a majority-owned subsidiary of CuraGen Corporation (NASDAQ: CRGN).

Description of Proposed Sequencing Methodology:

454 Sequencing enables one individual to prepare and sequence an entire genome after performing a single sample preparation, irrespective of the size of the genome being studied. The speed of our 454 Sequencing System derives from both our proprietary, emulsion-based, clonal amplification process, or emPCRâ„¢, as well as the simultaneous sequencing of hundreds of thousands of DNA molecules on the PicoTiterPlateâ„¢ used in our instrument. With emPCR, the first method for sample preparation that does not require bacterial cloning, millions of individual fragments of DNA are clonally amplified simultaneously, in an average of eight hours of laboratory time. One library preparation is sufficient for sequencing an entire genome, whether a virus, bacteria or human. The PicoTiterPlate is a glass plate consisting of 1.6 million individual 75 picoliter wells into which DNA fragments are deposited and on which sequencing occurs. 454 Sequencing uses a sequencing-by-synthesis approach to generate sequence data. The chemicals generated during nucleotide incorporation are converted into light in a chemi-luminescent reaction similar to that used by a firefly. Currently a single instrument produces over 20 million nucleotide bases per five-hour run. Our approach will be to increase the density of the sequencing reactions on the PicoTiterPlate, increase the individual read lengths and reduce the cycle times and the enzyme costs in order to reach the X PRIZE goal of $10,000 to sequence an individual human genome.

Team Quote:

We are excited to compete for the X PRIZE, as it promises to yield significant insight into human biology and ultimately to enable personalized medicine.

The X PRIZE for Genomics validates our vision that there will be significant value to improved human health from being able to routinely sequence human genomes. The ambitious goal of this project is in alignment with our efforts to continuously improve the capabilities and performance of 454 Sequencing, including to economically sequence any genome with unparalleled speed, throughput and accuracy.

Unlike some of the novel approaches being pursued by other teams, 454 Sequencing is proven. 454 Sequencing has already been used to better understand cancer genes and what treatment will work best for a specific patient. We sequence hundreds of thousands of DNA molecules simultaneously on this single glass slide. We intend to continue to increase the chip density, just like Moore’s Law did in computers.

The X PRIZE competition is valuable in raising public awareness of current and impending technology breakthroughs that promise to change society. We expect that society will benefit from improvements in DNA sequencing even before anyone might attain the X PRIZE for Genomics.

Winning this X PRIZE will require a long-term, dedicated effort and we believe that we have such a talented and committed team here at 454.