BioCentury
ARTICLE | Preclinical News

Bradner, Gray explore targeted degradation-based model systems

March 26, 2018 4:04 PM UTC

C4 Therapeutics Inc. co-founders James Bradner and Nathanael Gray published a paper in Nature Chemical Biology demonstrating a generalizable target-specific protein degradation system that can be used to create preclinical models that offer better control over a protein's expression than traditional genetic or pharmacological approaches (see BioCentury Innovations, March 26).
Bradner is president of the Novartis Institutes for BioMedical Research (NIBR). Gray is a professor of cancer biology at Dana-Farber Cancer Institute and a professor of biological chemistry and molecular pharmacology at Harvard Medical School.

Bradner, Gray and colleagues engineered genetic constructs comprising a target protein of interest fused to FK506 binding protein 1A 12kDa (FKBP1A; FKBP12), which served as a binding site for ligands dubbed degradation tags (dTAGs). After binding to the fusion protein, the dTAG links it to E3 ubiquitin ligase cereblon (CRBN), which triggers ubiquitination and proteosomal degradation. ...