Tumor-Specific RNA Editing Nanomedicine Activated by Wnt Signaling for Methionine Metabolic Immunotherapy

However, selectively targeting methionine metabolism in tumors remains challenging. Here, we develop a Wnt-activated RNA editing nanoplatform (TREND) to specifically disrupt the tumor methionine transporter SLC43A2 and reprogram the metabolic competition between tumor cells and CD8+ T cells.

By taking advantages of aberrant Wnt signaling pathway in tumor cells, we first established a Wnt-responsive promoter which was used to control the transcription of the plasmid encoding RNA editor (CasRx) targeting SLC43A2, in order to ensure RNA editing in tumor cells with activated Wnt signaling. To further promote the accumulation and the intracellular translocation of CasRx in the tumor cells in vivo, a tumor-targeted delivery system was engineered by cloaking hybrid cell membrane over the polymeric carriers for the systemic delivery of CasRx plasmid.