What is an aTAG?
aTAG is short for Achille’s TAG. We developed the aTAG system as a tool to enable understanding the consequences of target protein degradation.
Similarly to other chemical genetic systems, there is universal applicability to any target protein of interest via introduction of a small protein domain onto the target protein, forming a chimeric protein. This domain allows the target protein levels to be controlled by a universal degrader molecule.
C4T’s system is unique in the choice of the protein domains that facilitate degradation and we also produced high-potency molecules that act rapidly and that can be used both In vitro and in vivo settings.
How The aTAG System works:
The aTAG system is comprised of two components:
C4T’s aTAG system comprises two components: a small protein domain (the aTAG) that can be readily fused to a target protein and degrader molecules directed to the aTAG.
The protein domain is based on MTH1 and is only 17kDa in size. While the normal physiologic role of MTH1 is the enzymatic hydrolysis of 8-oxo-dGTP, there is no known consequence of the loss of this protein:
▪ NUDT1-/- mice show no phenotype
▪ Acute inhibition, or degradation, of MTH1 shows no cellular phenotype
Multiple optimized degraders for the MTH1 aTAG are available.
These degraders are highly potent, rapid-acting, and have a range of properties suitable for in vitro and in vivo applications.
APPLICATIONS FOR THE aTAG SYSTEM
We developed the aTAG system for a number of purposes and we are sure there are myriad more! Possible applications include:
- Understanding the biological consequences of target loss. The aTAG technology allows acute, specific degradation of a target protein to determine its biological implications.
- Degrader-driven target validation. The aTAG system provides and ability ability to determine the consequences of removing the protein can inform the attractiveness of the target for drug development.
- Control of engineered systems such as chimeric antigen receptors. The aTAG system can be used to modulate the levels of fusion proteins used in T-cell and related therapies.