e14076Background: Each miRNA modulates the expression of hundreds of genes across distinct cellular pathways, giving miRNA-based cancer therapy the potential to simultaneously repress multiple oncogenic processes in the tumor microenvironment, including growth and proliferation, resistance, cancer stem cells, metastasis, and immune evasion. The naturally occurring tumor suppressor miR-34a has been shown to down-regulate expression of > 30 oncogenes, as well as genes involved in tumor immune evasion (eg, PD-L1). MRX34, a liposome-encapsulated miR-34a mimic, is a potential first-in-class miRNA therapy for cancer. Methods: MRX34 activity was characterized in NOD/SCID mice with orthotopic liver tumors (Hep3B, HuH7, C3A, BN118, BN124). Biodistribution and biological activity were assessed using qRT-PCR and mRNA array analyses of tumor and tissues harvested 24 h after single IV injections of MRX34. In further experiments, we used serum AFP levels and recovered tumor weights to measure MRX34 efficacy, both as a ...