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Sigma-Aldrich makes technology for breakthrough “knockout” research

Written on July 25, 2009

Technology manufactured by Sigma-Aldrich Corp. has been used to generate rats with permanent heritable gene mutations, paving the way for the development of new human disease models, according to a new study.

The success is important to Sigma-Aldrich, which makes fine chemicals and products for scientific research, because the St. Louis-based company sees enormous potential in a technology that can precisely manipulate the genome of living organisms. The ability to selectively modify or control specific genes is emerging as a critical tool in modern biotechnology.

The report, published in Friday’s issue of Science, says this is the first time that zinc finger nuclease (ZFN) technology has been used to create a "knockout" mammal in which one or more genes have been "knocked out" or removed. The purpose of these genetic modifications is to create animals that will develop diseases similar to those found in humans. This allows researchers to better understand and treat these conditions.

ZFN technology will speed up the reproduction of such animals and it opens up new research avenues in rats, which are better models for hypertension, cardiovascular and certain other diseases. Previously all "knockout" animals were mice, said David Smoller, president of Sigma-Aldrich’s biotech business unit life insurance companies.

"It’s amazing what this will do for research," Smoller said. "This is exciting, revolutionary technology that will help us understand life."

The Science report is a result of concurrent research at the Medical College of Wisconsin and California-based Open Monoclonal Technology.

ZFNs are engineered proteins that induce double strand breaks at specific sites in an organism’s DNA. These breaks can result in site-specific changes in the DNA sequence. Previously, ZFNs were used to eliminate specific genes in fruit flies, worms, cultured human cells and zebrafish embryos. However, this research is the first successful example of ZFN being used to edit genes in mammalian embryos.

Sigma-Aldrich acquired the license for the ZFN technology, which was developed by Sangamo Biosciences Inc. Sigma-Aldrich produces the protein in St. Louis and markets it through the company’s CompoZr line of products.

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