ST. LOUIS, Dec. 13, 2010 /PRNewswire-FirstCall/ — Sigma Life Science, the innovative biological products and services business of Sigma-Aldrich® (Nasdaq: SIAL), today announced that its SAGE Labs initiative has successfully used its proprietary CompoZr® Zinc Finger Nuclease (ZFN) technology to generate knock-in rats in which foreign genes have been inserted, or ‘knocked-in’, into the rat genome in a precisely targeted manner. This breakthrough achievement represents a major step forward in the creation of a transgenic animal, which may serve as more predictive models of human disease.

In a proof of concept study conducted by researchers at SAGE Labs, a copy of the green fluorescent protein (GFP) was inserted in a targeted fashion into the Mdr1a gene of a rat, thus creating a rat that glows under special lighting conditions. The study, which has recently been accepted for publication(1), opens the doors to a variety of new applications including the tagging of genes with reporters such as GFP to measure gene expression patterns and replacement of rat genes with humanized versions.

Although rats have long been the model organism of choice for disease research, scientists have been forced to use mouse models for over a quarter of a century, due to their amenability to genetic manipulation. The creation of rats with gene deletions, commonly called ‘knock-outs’, using ZFN technology was first published in Science in 2009(2), and the ability to create rats with new genes introduced in their genome represents a leap forward in ZFN technology, allowing sophisticated genetic engineering of higher level organisms and providing scientists with a choice of model organisms that can be used to investigate different diseases.

Sigma Life Science’s CompoZr® ZFN technology is the only technique that has repeatedly been shown to make highly targeted mutations, and this breakthrough from SAGE™ Labs puts ZFN technology on par with classic ES cell-based gene targeting techniques in terms of application flexibility. SAGE Labs will use this technology, combined with its SAGEspeed™ model creation process, to produce a number of off-the-shelf rat models for use in the study of human diseases, as well as custom models for customers.

“We have invested time and resources in developing the CompoZr and SAGEspeed platforms to help realize the enormous potential of this technology, enabling precise manipulation of the genome of living organisms,” said Dr. Edward Weinstein, Director of SAGE Labs at Sigma Life Science. “This exciting advance is another example of how Sigma Life Science is pushing the limits of technology, establishing what we believe will become the new standard for the creation of genetically engineered research animals.”

For more information on SAGE Labs, please visit http://www.sageresearchmodels.com.

Cautionary statement: The foregoing release contains forward-looking statements that can be identified by terminology such as “represent a major step,” “may serve,” “opens the doors,” “will become” or similar expressions, or by expressed or implied discussions regarding potential future revenues from products derived therefrom. You should not place undue reliance on these statements. Such forward-looking statements reflect the current views of management regarding future events, and involve known and unknown risks, uncertainties and other factors that may cause actual results to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that knock-in rats will achieve any particular levels of revenue in the future. In particular, management’s expectations regarding knock-in rats could be affected by, among other things, unexpected regulatory actions or delays or government regulation generally; the Company’s ability to obtain or maintain patent or other proprietary intellectual property protection; competition in general; government, industry and general public pricing pressures; the impact that the foregoing factors could have on the values attributed to the Company’s assets and liabilities as recorded in its consolidated balance sheet, and other risks and factors referred to in Sigma-Aldrich’s current Form 10-K on file with the US Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected. Sigma- Aldrich is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.

About Sigma Life Science: Sigma Life Science is a Sigma-Aldrich business that represents the Company’s leadership in innovative biological products and services for the global life science market and offers an array of biologically-rich products and reagents that researchers use in scientific investigation. Product areas include biomolecules, genomics and functional genomics, cells and cell-based assays, transgenics, protein assays, stem cell research, epigenetics and custom services/oligonucleotides. Sigma Life Science also provides an extensive range critical bioessentials like biochemicals, antibiotics, buffers, carbohydrates, enzymes, forensic tools, hematology and histology, nucleotides, amino acids and their derivatives, and cell culture media. For more information about Sigma Life Science, please visit our Web sites at Where Bio Begins and Sigma Life Science.

About Sigma-Aldrich: Sigma-Aldrich is a leading Life Science and High Technology company committed to Enabling Science to Improve the Quality of Life. Its chemical and biochemical products and kits are used in scientific research, including genomic and proteomic research, biotechnology, pharmaceutical development and as key components in pharmaceutical, diagnostic and other high technology manufacturing. The Company has customers in life science companies, university and government institutions, hospitals, and in industry. Over one million scientists and technologists use its products. Sigma-Aldrich operates in 40 countries and has 7,700 employees providing excellent service worldwide. For more information about Sigma-Aldrich, please visit its award-winning Web site at http://www.sigma-aldrich.com.

1. Cui, X. (2010). Targeted integration in rat and mouse embryos with zinc finger nucleases. Nature Biotech.

2. Science 2009

Sigma-Aldrich, Sigma, SAGE, CompoZr and SAGEspeed are trademarks of Sigma-Aldrich Biotechnology L.P. and Sigma-Aldrich Co.

SOURCE Sigma-Aldrich

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“This is a very exciting joint effort,” said Dr Nathan Trinklein, CEO and co-founder of SwitchGear Genomics. “We believe that combining unique technologies from SwitchGear Genomics with Sigma’s industry-leading lentiviral technology and production capabilities will enable researchers to study miRNA function and gene regulation on an unprecedented scale.”

The genome-wide collection of reporter vectors is expected to provide highly effective miRNA target validation without the need for time-consuming and laborious reporter cloning. Use of Sigma’s patented lentiviral technology is expected to allow the highly regarded SwitchGear GoClone™ miRNA target sets to be used in a broad range of cell types, including primary cells and stem cells.

“We are excited to partner with SwitchGear Genomics on the co-development of this unique vector system,” added Dr. Supriya Shivakumar, Global Commercial Marketing Manager for Functional Genomics at Sigma Life Science. “By offering this novel reporter technology in a lentiviral format we are addressing specific customer needs and we believe we are helping to further fundamental understanding of gene regulation.”

St. Louis, MO. – August 5, 2010 – Sigma-Aldrich® (NASDAQ: SIAL) today announced it has entered into an agreement with the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health, and Boston University (BU) to develop methods to measure several potential biomarkers of atherosclerotic cardiovascular disease (CVD) using plasma samples from the NHLBI’s Framingham Heart Study (FHS), one of the most prestigious clinical studies in medicine. Funding for the project is provided by the NHLBI to Sigma-Aldrich under a research subaward agreement with BU.

The FHS began in 1948 as a study of more than 5,000 residents of Framingham, Massachusetts, to identify the factors that increase the risk for CVD. Since then, it has expanded to include over 14,000 participants from three generations within families. Using the results of FHS, researchers have identified a host of risk factors, including high blood cholesterol levels, elevated blood pressure, smoking, diabetes and obesity. The FHS is funded by the NHLBI and conducted in collaboration with BU’s School of Medicine and School of Public Health.

Sigma® Life Science, the innovative biological products and services business of Sigma-Aldrich, plans to work with NHLBI and BU to provide for the analysis of plasma samples from 7,000 participants to investigate 180 potential biomarkers for CVD. Over the course of this five-year project, Sigma Life Science expects to develop antibody reagents for each identified target biomarker and incorporate the reagents into a multiplexed, high-throughput platform to measure the proteins of interest.

“Through this project, Sigma Life Science, the NHLBI and BU are furthering insight into a number of important CVD targets,” said Dave Smoller, President of Sigma-Aldrich’s Research Biotech Business Unit. “By embarking on this exciting effort, we believe we will help to develop the next generation of biomarker technologies for life science research and therapeutic applications, and provide greater understanding into the genetics and biological pathways of heart disease. The project is expected to facilitate the development of diagnostic tools for the early detection and prevention of CVD, as well as therapies for early treatment. We are hopeful that establishing valid surrogate biomarkers will also be useful in the development of more individualized treatments for patients.”

The new project is part of a major FHS initiative called the Systems Approach to Biomarker Research in Cardiovascular Disease (SABRe CVD), which expects to identify and validate new CVD biomarkers, which in turn could ultimately lead to the development of blood tests to identify individuals at high risk of heart disease and stroke. Only information from FHS participants who have consented to sharing their specimens and data for genetic research will be used, and no shared information will be attributed to a specific participant to protect participants’ privacy. Data from these studies will be accessible to other scientists through dbGAP (Database for Genotype and Phenotype), in accordance with data-sharing policies.

“We believe this research will accelerate the development of new diagnostics and treatments for common life-threatening conditions,” said Karen Antman, M.D., Dean of Boston University School of Medicine. “Our faculty takes great pride in being part of this exciting research which may improve the lives of millions of people globally for the better,” she added.

The identification of antibody reagents specific to CVD biomarkers is expected to further expand Sigma Life Science’s growing portfolio of over 38,000 monoclonal and polyclonal antibodies. In addition, the Company offers 8,300 highly validated Prestige Antibodies®, covering over 6,900 human protein targets identified by the Human Proteome Resource. More information can be found online at: http://www.wherebiobegins.com/biomolecules/products/antibodies.