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 publication¹, 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 2009², 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^TM 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^TM 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.

1. Cui, X. (2010). Targeted integration in rat and mouse embryos with zinc finger nucleases. Nature Biotech, Advanced Online Publication - http://www.nature.com/nbt/journal/vaop/ncurrent/full/nbt.1731.html

2. Science 2009 

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