Transient mRNA-based immune shielding of the liver to prevent cancer metastasis

Our project addresses a major unmet need in oncology: the prevention of liver metastasis, a leading cause of cancer-related mortality and a dominant site of relapse in colorectal cancer. After detaching from the primary tumor and entering the circulation, disseminating cancer cells preferentially seed the liver, exploiting its uniquely permissive microenvironment to initiate metastatic outgrowth. Here, we propose an mRNA-based strategy to reprogram hepatic cells in situ, modifying the local microenvironment to become resistant to metastatic colonization. By transiently engineering liver cells to form a protective biological “shield,” this approach aims to intercept circulating tumor cells and prevent their expansion into secondary lesions. This targeted gene-therapeutic intervention is designed to circumvent the systemic toxicity associated with chemotherapy while substantially reducing the risk of liver metastasis following surgical removal of the primary tumor, thereby opening new translational opportunities to improve long-term outcomes in patients at high risk of metastatic recurrence.