Sigma Life Science, a Sigma-Aldrich brand, extended its portfolio of knockout rat models with the announcement of a new suite of models designed to facilitate more predictive absorption, distribution, metabolism, excretion and toxicity (ADME/Tox) studies. This extension of the Company’s product offering, the first ever models created especially for ADME/Tox applications, is expected to help researchers establish the efficacy of drugs more rapidly and with greater accuracy, due to the rat’s ability to better model human physiology when compared to mouse models currently used.
The four new models were developed by Sigma Advanced Genetic Engineering (SAGE) Labs, a Sigma Life Science initiative, and have single gene deletions to well-established drug transporters: Mdr1a (P-glycoprotein), Mrp1 (Multiple drug resistance-associated protein 1), Mrp2 (Multiple drug resistance-associated protein 2), Pxr (Pregnane X receptor), and Bcrp (Breast cancer resistance protein). The validated Mdr1a knockout model is currently available for purchase, while the other models are expected to be available for purchase later this year.
“Until now, the availability of relevant, genetically modified rats was limited. Knockout mice are readily available, but very challenging to use in ADME/Tox applications due to their size and physiology. We’ve changed that,” commented Dr. Edward Weinstein, director of SAGE Labs. “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-glycopotein (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 (ZFN) gene editing technology, which enables scientists to deactivate or “knockout” specific genes that are associated with human disease.
SAGE Labs is the premier resource for genetically modified rodent disease models and markets its exclusive SAGEspeed Custom Model Development program for the creation of knockout mouse or rat models in as little as five months. The group is also developing their catalog of knockout rat models across a number of research fields, including Neurobiology, Toxicology, Cardiology and Immunology.