We leveraged an ionizable lipid that is alreadyused in an FDA-approved siRNA therapeutic22 to package a 3p-modified, stem-loop RNA (SLR) that we have engineeredto be a molecularly defined, selective, and high-affinity RIG-I agonist.11 We found that SLR-loaded LNPs (SLR-LNP) inhibitedtumor growth and increased the response to ICIs in poorly immunogenic,orthotopic mouse models of breast cancer and melanoma. This evidence concerns the gene RIGI and breast carcinoma.