While one model is already available, three more will be introduced later this year.

Sigma-Aldrich will be offering a suite of knockout rat models designed to facilitate more predictive ADME/Tox studies. The four new models were developed by Sigma Advanced Genetic Engineering Labs (SAGE™) and have single gene deletions to well-established drug transporters Mdr1a, Mrp1, Mrp2, Pxr, and Bcrp. The Mdr1a knockout model is currently available for purchase, while the other models are expected to be available for purchase later this year.

“Knockout mice are readily available, but very challenging to use in ADME/Tox applications due to their size and physiology,” points out Edward Weinstein, Ph.D., director of SAGE Labs. “We’ve changed that. Our knockout rat models offer a platform that can potentially save millions of dollars in development costs for potential drug candidates by providing a more human-like model and, at the same time, significantly decrease time to market for these therapeutics.

“A rat that is deficient in P-glycoprotein (PGP) expression, for example, serves as an improved model over the existing mouse model due to its metabolism and physiology, making it more predictive of how a drug will behave in humans. This is of huge benefit to drug discovery, enabling researchers to go back and address issues much sooner than they can today.”

The latest knockout rat models were developed using Sigma-Aldrich’s CompoZr™ Zinc Finger Nuclease gene-editing technology, which enables scientists to deactivate specific genes that are associated with human disease. SAGE Labs markets its exclusive SAGEspeed™ Custom Model Development program for the creation of knockout mouse or rat models in five months. The group is also developing a catalog of knockout rat models across a number of research fields including neurobiology, toxicology, cardiology, and immunology.

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