Concept

454 Life Sciences

454 Life Sciences was a biotechnology company based in Branford, Connecticut that specialized in high-throughput DNA sequencing. It was acquired by Roche in 2007 and shut down by Roche in 2013 when its technology became noncompetitive, although production continued until mid-2016. 454 Life Sciences was founded by Jonathan Rothberg and was originally known as 454 Corporation, a subsidiary of CuraGen. For their method for low-cost gene sequencing, 454 Life Sciences was awarded the Wall Street Journal's Gold Medal for Innovation in the Biotech-Medical category in 2005. The name 454 was the code name by which the project was referred to at CuraGen, and the numbers have no known special meaning. In November 2006, Rothberg, Michael Egholm, and colleagues at 454 published a cover article with Svante Pääbo in Nature describing the first million base pairs of the Neanderthal genome, and initiated the Neanderthal Genome Project to complete the sequence of the Neanderthal genome by 2009. In late March 2007, Roche Diagnostics acquired 454 Life Sciences for US$154.9 million. It remained a separate business unit. In October 2013, Roche announced that it would shut down 454, and stop supporting the platform by mid-2016. In May 2007, 454 published the results of Project "Jim": the sequencing of the genome of James Watson, co-discoverer of the structure of DNA. 454 Sequencing used a large-scale parallel pyrosequencing system capable of sequencing roughly 400-600 megabases of DNA per 10-hour run on the Genome Sequencer FLX with GS FLX Titanium series reagents. The system relied on fixing nebulized and adapter-ligated DNA fragments to small DNA-capture beads in a water-in-oil emulsion. The DNA fixed to these beads was then amplified by PCR. Each DNA-bound bead was placed into a ~29 μm well on a PicoTiterPlate, a fiber optic chip. A mix of enzymes such as DNA polymerase, ATP sulfurylase, and luciferase was also packed into the well. The PicoTiterPlate was then placed into the GS FLX System for sequencing.

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