454 Sequencing™ reveals new pathway in RNA interference

Application by Cold Spring Harbor Laboratory yields new insights on DNA methylation

BRANFORD, Conn., October 25, 2006 -- CuraGen Corporation's (NASDAQ: CRGN) majority-owned subsidiary 454 Life Sciences today announced that research on small RNAs, conducted by Cold Spring Harbor Laboratory, has revealed the dual role of the ARGONAUTE 4 protein (AGO4) in RNA-directed DNA methylation. The research, which describes a method for obtaining a comprehensive view of the total small RNAs from a single sample, was published today in Nature. The study, entitled, "Distinct Catalytic and Non-Catalytic Roles of ARGONAUTE4 in RNA-directed DNA Methylation," describes how 454 SequencingTM was used to elucidate the small RNAs associated with AGO4 and the AGO1 protein.

"Small RNAs have emerged as a means of genetic control that were completely unsuspected only 10 years ago. Virtually every area of biology has been affected by the discovery of these pathways. What we are now finding is that the diversity of small RNAs in many systems is even greater than previously suspected. The new study shows this in Arabidopsis (a model plant), where small RNAs have a major role in controlling the epigenetic organization of the entire genome," said Gregory Hannon of Cold Spring Harbor Laboratory, who led the research. "Conventional DNA sequencing methods gave us glimpses of the various classes of small RNAs that exist in plants and animals. However, only with 454 Sequencing have we been able to fully appreciate the extent of small RNA populations and the breadth of biological processes they might affect," Dr. Hannon noted.

"The Genome Sequencer 20TM system allows researchers to rapidly characterize all of the small RNAs in their samples," said Michael Egholm, Ph.D., Vice President, Molecular Biology, 454 Life Sciences. "454 Sequencing offers high quality, fast and accurate sequencing of small RNAs which has revolutionized research in the mechanisms of RNA interference."

The role of small RNAs is an exciting and rapidly growing field of research that is benefiting from technical advances in comprehensive and rapid sequencing. Small RNAs have several biological functions essential for cell growth and development. They regulate mRNA stability and protein synthesis, cause post-transcriptional gene silencing of transposons, viruses and transgenes, and regulate chromatin organization and genome structure. This is the second paper by Dr. Hannon on the use of 454 Sequencing to study small RNA to be published by Nature. In recent months, several other research teams using 454 Sequencing to study small RNA in plants, mammals, and viruses have had their findings published in Science, Nature Genetics, Journal of Virology, and Genome Research. Dr. Hannon has generously made the protocol for his method utilizing 454 Sequencing available for download at www.454.com.

The Genome Sequencer 20TM system (GS 20) is exclusively distributed for 454 Life Sciences by Roche Applied Science, a division of Roche Diagnostics. Visit the Roche Diagnostics website for more information on purchasing 454 products at http://www.roche-applied-science.com.


About 454 Life Sciences
454 Life Sciences, established in 2000 as a majority-owned subsidiary of CuraGen Corporation (NASDAQ: CRGN), develops and commercializes novel instrumentation for high-throughput nucleotide sequencing, with specific application to whole-genome sequencing and ultra-deep sequencing of target genes. The hallmarks of 454 SequencingTM are its simple, unbiased sample preparation and massively parallel sequencing, which makes large-scale scientific projects feasible and more affordable. The Genome Sequencer 20TM System enables one individual to prepare and sequence an entire genome, regardless of size. A single instrument using patented light emitting sequencing chemistries produces over 20 million nucleotide bases per five-hour run, more than 60 times the capacity of currently available instruments. In 2005, 454 Sequencing and the Genome Sequencer 20 System won The Wall Street Journal's top Innovation Award for 2005, and received an R&D 100 Award as one of the most technologically significant products introduced in 2006. The 454 Sequencing Center offers sequencing services directly to customers on a fee for service basis. The Genome Sequencer 20 system is exclusively distributed for 454 Life Sciences by Roche Applied Science, a division of Roche Diagnostics. For additional information please visit http://www.454.com.

Safe Harbor
This press release contains forward-looking statements that are subject to certain risks and uncertainties. These forward-looking statements include statements regarding future expectations, beliefs, intentions, goals, strategies, plans or prospects regarding the future, including the future effect of 454 Sequencing on research in the mechanisms of RNA interference. Such statements are based on management's current expectations and are subject to a number of risks and uncertainties that could cause actual results to differ materially from those described in the forward-looking statements. 454 Life Sciences and CuraGen caution investors that there can be no assurance that actual results or business conditions will not differ materially from those projected or suggested in such forward-looking statements as a result of various factors, including, but not limited to, the following: the early stage of development of 454 Life Sciences' products and technologies; customer acceptance of 454 Life Sciences' products and technologies; 454 Life Sciences' ability to scale-up production of its products and technologies; disputes between 454 Life Sciences and CuraGen; the success of competing products and technologies; technological uncertainty and product development risks; uncertainties of clinical trials, government regulation and healthcare reform; uncertainty of additional funding with respect to both CuraGen and 454 Life Sciences; 454 Life Sciences' and CuraGen's history of incurring losses and the uncertainty of achieving profitability; CuraGen's stage of development as a biopharmaceutical company; patent infringement claims against 454 Life Sciences' and CuraGen's products, processes and technologies; the ability to protect 454 Life Sciences' and CuraGen's patents and proprietary rights; uncertainties relating to commercialization rights; product liability exposure; and competition. Please refer to CuraGen's Annual and Quarterly Reports on Forms 10-K and 10-Q for a complete description of these risks. 454 Life Sciences and CuraGen disclaim any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events, or otherwise.

454® is a registered trademark of 454 Life Sciences Corporation. 454 Life SciencesTM, Genome Sequencer 20TM, PicoTiterPlateTM, and 454 SequencingTM are trademarks of 454 Life Sciences Corporation.

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