Unlocking the Immune System

Researchers at MD Anderson and Arcturus Therapeutics describe using microRNA to activate the immune system against glioma - a devastating brain cancer. In previous work, MD Anderson researchers discovered the microRNA miR-124 was drastically suppressed in glioma compared to healthy neurons, and their work identified a link to how glioma evades the immune system. In this work, published in the March 2017 issue of the journal Neuro-Oncology, the authors encapsulated miR-124 mimics into lipid nanoparticles (LNPs) using NanoAssemblr Technology. Treating glioma-bearing murine models with miR-124-LNPs unleashed the immune system to fight glioma. This not only improved survival, but also imparted lasting protection from a second glioma challenge. Additionally, this formulation acts on peripheral blood mononuclear cells and does not need to cross the blood brain barrier to be effective. This constitutes an exciting immuno-oncology treatment for glioma that provides lasting protection against relapse with a single treatment, while proving to be safe in multiple species.

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Selectively Programming Cancer Cell Death

Apoptotic proteins can be used to signal cells to self-destruct. The challenge in using them for cancer therapy has been selectively targeting these signals exclusively to cancer cells without harming healthy cells. In a 2018 paper published in the journal Nucleic Acid Therapeutics, researchers at Moderna Therapeutics report overcoming this challenge. Their approach involved delivering mRNA encoding apoptotic proteins and delivering these to the liver using lipid nanoparticles formulated with NanoAssemblr technology. To control expression of the toxic protein, they analyzed differences in microRNA (miRNA) expression levels between healthy and cancerous liver cells and incorporated miRNA binding sites into their mRNA sequence. When the mRNA encoding the toxic protein is taken up by healthy cells, endogenous miRNAs bind to them, marking them for destruction through the RNA interference pathway before the protein can be expressed. In cancerous cells where these miRNAs are down regulated, the delivered mRNA is translated into toxic proteins. Hence tumour cells are selectively programmed to self-destruct. This constitutes a highly selective way to express exogenous proteins in cancer cells, opening new avenues for treatment.

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