Sigma® Life Science Creates World's First Knock-in Rats using Zinc Finger Nuclease Technology

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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