The medical use of mRNA to direct the intracellular expression of therapeutic proteins is rapidly evolving into a key area of research and development in biotechnology, and scientists and pharmaceutical companies around the world are developing drugs based on this class of biomolecule. Innovative therapeutic treatment options for diseases such as cancer, cardiovascular or metabolic diseases or infectious diseases such as influenza are under development.
mRNA molecules are large, fragile and easily degrade. They do not readily cross plasma membranes to enter target cells and so a delivery solution is required. By leveraging improvements in LNP technology garnered through Arbutus’ RNAi trigger molecule development programs, we have made substantial improvements in mRNA delivery, positioning us to enable the development of mRNA therapeutics by our partners.
The above slide demonstrates potent mRNA delivery with Third Generation LNP in vivo. Micrographs of liver sections (DAPI-stained cell nuclei appearing blue) from mice treated with LNP containing mCherry transcripts are displayed in the bottom row. Significantly more activity (red fluorescence) is observed when using Third Generation LNP technology compared to Second Generation formulations (including clinically validated MC3-LNP). No activity is observed in the negative controls (top row).
Our proprietary manufacturing methodology is believed to be the only truly scalable method permitting highly reproducible mRNA encapsulation under conditions suitable for product development purposes. Typically, regulatory authorities require greater than 90% encapsulation for GMP product development, a readily attainable target using Arbutus’ inherently scalable process. We have also incorporated the latest generation of lipid technology. The result is a more robust manufacturing process, increased encapsulation efficiency, and a substantial increase in mRNA potency.