Molecular therapy. Nucleic acidsJul 13, 2026

mRNA nanoparticles delivered through the bloodstream enter main and spreading liver tumors

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗

Updated Jul 14, 2026

Abstract

Intravenous delivery of mRNA lipid nanoparticles efficiently transfects virtually all hepatocytes in various liver conditions.

mRNA lipid nanoparticles can be delivered systemically to the liver.
Most liver cells in healthy, fibrotic, and cirrhotic conditions take up the mRNA effectively.
Many cells in spontaneous liver tumors are also transfected with the delivered mRNA.
In xenograft models of primary and secondary liver cancer, mRNA delivery is achievable, though protein expression is reduced compared to normal liver.
These results suggest a potential for using mRNA therapies in treating liver diseases and cancers.

Simplified

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.

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Funding

Competing interests

T.R.M. and S.W.C. have received research funding from Oxford Nanopore Technologies, Sartorius Stedim Australia, and Sanofi. L.J.L., T.R.M., and S.W.C. have received support for conference attendance, travel, and accommodation from Moderna. No commercial entity was involved in this research.

PubMed

mRNA nanoparticles delivered through the bloodstream enter main and spreading liver tumors

Abstract

Full Text

Funding

Competing interests

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