Efficient delivery of mRNA-LNPs in primary and secondary liver cancer

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 tumours have limited efficacy and new treatment modalities have the potential to improve patient outcomes. mRNA therapeutics are readily delivered to the healthy liver after systemic administration, but their uptake and expression within liver tumours is unclear. Here we show that intravenous delivery of mRNA-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 to 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.