Cancer has emerged as the leading cause of human death globally. Recent research showed that RSPO protein hyperactivation can lead to a variety of human cancers. Targeted therapy has great potential for precision medicine because of its many advantages. Hence, we developed RTAC (RSPO-Targeting Anti-cancer Chimeric protein), a novel therapeutic strategy to combat RSPO-induced malignancies. And we engineered yeast with self-tunable RTAC delivery to colon tumors.
 |
 |
Inspired by the antibody-based therapeutic strategy, we employed gene editing and protein engineering to construct the novel chimeric fusion protein RTAC by merging domains from various proteins. After optimization and characterization, RTAC exhibits pan-RSPO binding affinity and inhibitory function and effectively antagonizes RSPO-dependent cancer growth.
 |
 |
We constructed a novel engineered yeast (R-yeast) as a therapeutic probiotic to particularly treat RSPO-dependent colon cancers. The expression of RTAC is triggered by the tumor microenvironment-specific molecule via the reprogrammed yeast mating route for self-tunable targeted drug release locally to the tumor cells. R-yeast can only function in the intestine without potential environmental biohazards thanks to our unique Cu2+-specific kill switch.
