Sigma Life Science said that the extension of its 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 latest knockout rat models were developed using Sigma-Aldrich’s proprietary CompoZr Zinc Finger Nuclease (ZFN) gene editing technology, which enables scientists to deactivate or knockout specific genes that are associated with human disease.
Edward Weinstein, director of SAGE Labs, said: “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.
“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.”