MicroRNAs are commonly dysregulated in cancer, contributing to tumour cell biology. This is also the case for malignant pleural mesothelioma (MPM), an asbestos-related cancer for which few treatments are available. Recently we demonstrated that members of the miR-15/16 family are downregulated and have tumor suppressor functions in MPM, results similar to previous findings in prostate and non-small cell lung cancer (NSCLC). Restoring levels of these microRNAs with mimics led to growth inhibition and induction of apoptosis of MPM cells in vitro. When packaged in bacterially-derived, EGFR antibody-targeted, EDVTMnanocells the miR-16 mimic was able to inhibit xenograft tumour growth in vivo. As multiple microRNAs from the same family are downregulated in MPM, we investigated the possibility of creating a synthetic mimic based on the consensus sequence of the entire family. Mimics derived from consensus sequences were subsequently compared with native miR-16 and found to have improved growth inhibitory activity in MPM and NSCLC lines, possibly due to altered affinity to major targets. The synthetic mimics were also active in vivo. Based on these preclinical studies a Phase I clinical trial has been initiated for patients with MPM or NSCLC failing standard therapy. This represents only the second trial of microRNA replacement as a cancer therapy, and the first for thoracic cancers.