Sigma Life Science knockout rat models for ADME/Tox applications

Sigma Life Science has extended its portfolio of knockout rat models with a suite of models designed to facilitate more predictive absorption, distribution, metabolism, excretion and toxicity (ADME/Tox) studies.

The models, created specifically for ADME/Tox applications, are 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 have single gene deletions to well-established drug transporters: P-glycoprotein (Mdr1a), multiple drug resistance-associated protein 1 (Mrp1), multiple drug resistance-associated protein 2 (Mrp2), pregnane X receptor (Pxr) and breast cancer resistance protein (Bcrp). The validated Mdr1a knockout model is currently available for purchase, while the other models are expected to be available for purchase later this year.

The models are claimed to offer a platform that can potentially save substantial development costs for potential drug candidates by providing a more human-like model and significantly decrease time to market. 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.

The knockout rat models were developed using the company’s CompoZr zinc finger nuclease (ZFN) gene editing technology that enables scientists to deactivate or ‘knockout’ specific genes that are associated with human disease.