W. Chen and H. Yang of University of Delaware have just introduced a bioPROTAC system for logic-gated, switchable targeted protein degradation.  With the help of splitFAST and FAST of The Twinkle Factory.

splitFAST for switchable TPD

splitFAST for switchable TPD – © 2024 The Authors

BioPROTACs are heterobifunctional proteins designed for targeted protein degradation (TPD).  They offer a therapeutic avenue for modulating disease-related proteins.  The authors have just introduced a synthetic framework for logic-gated, switchable TPD to achieve temporal control of protein content. By exploiting both the cleavage and ligation functionalities of Sortase A (SrtA), they utilize SrtA as the control input to direct bioPROTAC activity for switchable TPD. This new Logic-gated AdPROM deploying SrtA-mediated Element Recombination platform allows to expand protein degradation in mammalian cells using Boolean logic operations depending on the input combinations. The flexibility to temporally modulate the level of multiple native intracellular proteins can potentially lead to applications from therapy to diagnostics and biotechnology.

Interestingly, the authors implemented FAST and splitFAST in the preliminary design phase. Building on their capability to finely and reversibly  monitor the dynamics of protein-protein interactions, even in the most complex systems thanks to its small size.

The Twinkle Factory supplies a whole range of fluorogenic reporters for FAST and splitFAST, varying in colors and affinity.  The study reported above implemented the green HMBR or tfLime.  Aso available are the red tfCoral or the far-red tfPoppy.  Coming soon infra-red!  Stay tuned!!!

Stain different. Tag FAST!

More reading

Chen, W. and Yang, H., 2024. Synthetic protein degradation circuits using programmable cleavage and ligation by Sortase A. Research Square June 26th, 2024. (https://doi.org/10.21203/rs.3.rs-4583684/v1)