MRX34

Approaches include targeting viral transcripts directly (e.g., siRNAs against HBV surface antigen) or host factors critical for viral replication (e.g., anti-miR-122 miravirsen for HCV)...These include TargomiR (a miR-16 mimic for mesothelioma), cobomarsen (an anti-miR-155 for lymphomas), and MRX34 (a miR-34a mimic for various solid tumours)...Despite promising preclinical results, clinical translation has been hampered by issues like insufficient delivery efficiency to human tumours, toxicity, and the complex, interconnected regulatory networks of miRNAs, which can lead to unpredictable off-target effects. While RNA therapeutics hold immense promise, overcoming delivery barriers and enhancing understanding of RNA regulatory networks are essential for future success.

However, the clinical translation of miR-34a has been hindered by challenges such as poor stability, inefficient cytoplasmic delivery, and immune-related toxicities, as evidenced by the failure of MRX34 in trials...This dual mechanism promoted macrophage phagocytosis, enhanced CD8+ T-cell activation, and induced apoptosis, resulting in significant tumor inhibition without systemic toxicity. These findings demonstrate the transformative potential of aCD47-C-miR34a in overcoming TNBC's oncogenic and immune-evasive mechanisms, paving the way for innovative treatments in TNBC and other heterogeneous, aggressive cancers.

Clinical treatment drugs have been developed based on miR-34 and miR-122 (MRX34 and Miravirsen, respectively), but their side effects have not yet been overcome. Future research is needed to address these weaknesses and establish a feasible microRNA-based treatment strategy for liver cancer.