In recent years, messenger ribonucleic acid (mRNA) therapy has garnered significant interest and has been developed for the treatment of a range of diseases, including rare genetic disorders, neurodegenerative diseases, inflammation, cancer, and infectious diseases. Similar to DNA molecules, mRNA molecules have the potential to express any desired protein in diseased cells through the cell’s own protein synthesis machinery.

Unlike DNA, mRNA does not carry the risk of insertional mutations since its function does not require entry into the cell nucleus. However, due to non-specific ribonuclease activity or immunogenicity triggered by Toll-like receptor-mediated RNA recognition, mRNA is less stable than DNA and is susceptible to degradation both extracellularly and intracellularly.

Due to these limitations, until recent years, DNA has been more popular than mRNA in gene therapy development. Specifically, viral vectors and naked or plasmid DNA have been predominantly used for suicide gene therapy purposes, involving the intracellular expression of toxic proteins or enzymes to convert non-toxic compounds into cytotoxic molecules, inducing death in cancer cells.

Researchers from Tel Aviv University have published an article in the journal Theranostics titled “Lipid nanoparticles-loaded with toxin mRNA represents a new strategy for the treatment of solid tumors”.

Cancer treatment has seen significant progress in the past decade, providing new strategies to harness immune regulation to inhibit the growth of cancer cells, whether using gene therapy or not. Specifically, suicide gene therapy and immunotoxins have been studied for treating tumors through direct cytotoxicity to cancer cells. Recent advancements in mRNA delivery have also demonstrated the potential of mRNA-based vaccines and immune modulators for cancer treatment by utilizing nanocarriers to deliver mRNA.

The researchers designed a modified mRNA encoding a bacterial toxin, delivered to a B16 melanoma mouse model through lipid nanoparticles. They found that locally administered LNPs, encapsulating modified mRNA encoding a bacterial toxin, induced a significant anti-tumor effect and improved the overall survival rate of the treated mice. mRNA-loaded LNPs represent a new anti-tumor, toxin-based therapeutic approach.