Systemically delivered mRNA-LNPs transfect primary and secondary liver tumors.

Primary liver cancer is the sixth most prevalent cancer globally and is often diagnosed late, when treatment options are limited. Secondary liver cancer, arising from metastasis of other cancers to the liver, is a common complication of advanced solid cancers and a significant cause of cancer-related morbidity and mortality. Existing treatment options for advanced primary and secondary liver tumors have limited efficacy, and new treatment modalities have the potential to improve patient outcomes. Messenger RNA (mRNA) therapeutics are readily delivered to the healthy liver after systemic administration, but their uptake and expression within liver tumors are unclear. Here, we show that intravenous delivery of mRNA lipid nanoparticles (LNPs) efficiently transfects virtually all hepatocytes in healthy, fibrotic, and cirrhotic liver and also many cells of spontaneous hepatocellular carcinomas in situ. Delivery of mRNA is also possible in xenograft models of both primary and secondary liver cancer, albeit with attenuated protein expression relative to the normal liver. These findings demonstrate the potential for systemically delivered mRNA-LNP therapies for liver disease and cancer.