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Transplantation Safety: New Virus Detected Using Genome Sequencer Technology

Researchers at Columbia University and Victorian Infectious Disease Reference Laboratory have discovered a new virus that was responsible for the deaths of three transplant recipients.

Basel - February 8, 2008

454 Life Sciences, a part of Roche Applied Science, today announced that researchers at Columbia University and Victorian Infectious Disease Reference Laboratory have discovered a new virus that was responsible for the deaths of three transplant recipients. The research explains how the previously unknown virus, which is related to lymphocytic choreomeningitis virus, was found using the extremely rapid and sensitive 454 Sequencing™ technology and was published online today in New England Journal of Medicine. The study entitled, “Discovery and implication of a novel arenavirus in a cluster of fatal transplant associated disease,” describes how identification of this virus might enable improvements in screening that will enhance the safety of transplantation.

Following the deaths of all three recipients of organs from a single donor, their illnesses were investigated by unbiased high throughput 454 Sequencing to reveal the presence of a previously undiscovered old world arenavirus. The virus, similar to lymphocytic choreomeningitis virus and Kodoko virus, was subsequently confirmed in multiple clinical samples by PCR, viral culture and immunohistochemistry. Results of the study implicate this new arenavirus as a human pathogen and support the use of high throughput sequencing in pathogen discovery.

"Within a few days we had clues to the identity of the virus responsible for transplant deaths" said Ian Lipkin, MD, lead author of the study and John Snow Professor of Epidemiology and Professor of Neurology and Pathology at Columbia University and director of the Center for Infection and Immunity at the Mailman School of Public Health. "We made this investigation highest priority. Our success reflected the tireless efforts of an extraordinary team of investigators representing academia, public health and industry, who brought all of their expertise and technology to bear on an important clinical problem.”

“We are very satisfied to see that the Genome Sequencer System could quickly identify new viruses where other methods failed,” said Manfred Baier, Head of Roche Applied Science. “This is another example for the potential of the 454 sequencing technology in various application areas. The identification of the virus is an important first step in a further enhancing the safety of transplantations.”

“454 Sequencing enables researchers to quickly and affordably identify the organisms present in a complex sample without any prior knowledge” said Michael Egholm, PhD, study author and Vice President of Research and Development at 454 Life Sciences. “This metagenomics approach to pathogen identification, which has been enabled by the Genome Sequencer FLX, should facilitate a more rapid response when the next SARS or avian flu virus appears in the future.”

Lymphocytic choreomeningits virus has been implicated in other transplant outbreaks; however, the newly discovered virus is sufficiently different that it could not be detected using existing screening and traditional sequencing methods all requiring prior knowledge of exact sequence of the suspected pathogen. Over 30,000 organ transplants are performed in the U.S. each year. Knowledge of the genetic sequence of this virus might enable improvements in screening that will enhance the safety of transplantation.

454 Life Sciences develops and commercializes the innovative Genome Sequencer™ system for ultra-high-throughput DNA sequencing. Specific applications include de novo sequencing and re-sequencing of genomes, metagenomics, RNA analysis, and targeted sequencing of DNA regions of interest. The hallmarks of 454 Sequencing™ are its simple, unbiased sample preparation and long, highly accurate sequence reads, including paired reads. 454 Sequencing technology has enabled many peer-reviewed studies in diverse research fields such as cancer and infectious disease research, drug discovery, marine biology, anthropology, paleontology and many more.

About Roche

Headquartered in Basel, Switzerland, Roche is one of the world’s leading research-focused healthcare groups in the fields of pharmaceuticals and diagnostics. As the world’s biggest biotech company and an innovator of products and services for the early detection, prevention, diagnosis and treatment of diseases, the Group contributes on a broad range of fronts to improving people’s health and quality of life. Roche is the world leader in in-vitro diagnostics and drugs for cancer and transplantation, and is a market leader in virology. It is also active in other major therapeutic areas such as autoimmune diseases, inflammatory and metabolic disorders and diseases of the central nervous system. In 2007 sales by the Pharmaceuticals Division totalled 36.8 billion Swiss francs, and the Diagnostics Division posted sales of 9.3 billion francs. Roche has R&D agreements and strategic alliances with numerous partners, including majority ownership interests in Genentech and Chugai, and invested over 8 billion Swiss francs in R&D in 2007. Worldwide, the Group employs about 79,000 people. Additional information is available on the Internet at www.roche.com.

For more information on the technology, visit www.roche-applied-science.com/sis/sequencing.

For more information please contact

Roche Diagnostics GmbH

Dr. Burkhard Ziebolz

Phone +49 (8856) 60 4830

Email: burkhard.ziebolz@roche.com

454 Life Sciences

Brendon Hill

Phone: +1 203-871-2460

Email: brendon.hill@roche.com

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