Efficient delivery of mRNA-LNPs in primary and secondary liver cancer
Leighton, L. J.; Gee, Y. J.; Madugalle, S. U.; Victorova, M.; Carrodus, N. L.; Bridle, K. R.; Howell, S. A.; Liang, X.; Miller, G. C.; McMillan, C. L. D.; Wijesundara, D. K.; Muller, D. A.; Crawford, D. H. G.; Mercer, T. R.; Cheetham, S. W.
Show abstract
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.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Cholangiocytes contribute to hepatocyte regeneration after partial liver injury during growth spurt in zebrafish 95%
- Cancer cell genetics shaping of the tumor microenvironment reveals myeloid cell-centric exploitable vulnerabilities in hepatocellular carcinoma 95%
- A Paradoxical Tumor Antigen Specific Response in the Liver 95%
Similar papers in this journal
- Lactate transporter MCT1 in hepatic stellate cells promotes fibrotic collagen expression in nonalcoholic steatohepatitis 95%
- Elys deficiency constrains Kras-driven tumour burden by amplifying oncogenic stress 95%
- ME3BP-7 is a targeted cytotoxic agent that rapidly kills pancreatic cancer cells expressing high levels of monocarboxylate transporter MCT1 94%
Similar papers in this journal
- Hypoxia-Sensing CAR T-Cells Provide Safety and Efficacy in Treating Solid Tumors 94%
- Cardiolipin-mimic lipid nanoparticles without antibody modification delivered senolytic in-vivo CAR-T therapy for inflamm-aging 94%
- An Omic and Multidimensional Spatial Atlas from Serial Biopsies of an Evolving Metastatic Breast Cancer 92%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.