Manipulation of focal Wnt activity via synthetic cells in a double?humanized zebrafish model of tumorigenesis

The canonical Wnt signaling pathway is activated in numerous contexts, including normal and cancerous tissues. Here, we describe a synthetic cell-based therapeutic strategy that inhibits aberrant activity specific focuses without interfering with the tissues vivo. As proof of principle, generated triple transgenic zebrafish liver cancer model conditionally expressed human MET induced ectopic hepatocytes. Then, customized Notch receptor (synNotch) cascade to express inhibitor DKK1 Jurkat T cells peripheral blood mononuclear (PBMCs) after recognizing as antigen. After that, synNotch PBMCs were sorted microinjected into different model. In MET-expressing tissues, injected inhibited local proliferation activity; while yolk sac MET, remained inactive. Overall, our studies revealed use antigen receptors improve spatiotemporal accuracy anti-Wnt therapy, proposed genetically humanized may serve small-scale highly optically accessible platform for functional evaluation cells.