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6 Pharmaceutical Technology ® Innovations in mRNA eBook April 2024 PharmTech.com FORMUL ATION technologies being researched or developed with the same goals? De Koker (etherna): If you look at it, the vast ma- jorit y of mRNA drug products that are in clinical evaluation do use lipid-based nanoparticles, so, to date, it seems that these are the standard. They have now been established to a scalable manufacturing process, and they have great potency; their develop- ment has taken a couple of decades to arrive at a very potent LNP suite, which we have today. For at least the next 10 years, LNPs are clearly going to be the preferred delivery vehicles for mRNA. Of course, there are still a couple of challenges with LNPs. Af ter intravenous injection, for exam- ple, targeting different tissues than the liver is still a major challenge. So typically, if you inject mRNA LNPs intravenously, 99 or 95% of them end up in the liver and are expressed by hepatocytes, so this limits the applicability of mRNA drugs. There is progress being made to also, for example, target the lungs, [where] mRNA LNPs are typically nebulized. There, they can transfect bacterial cells, and this is import- ant for many rare diseases [such as] cystic fibrosis and so on, when you want to bring in the mRNA pay- loads into the lung epithelium. Af ter intravenous administration, there is also much progress being made to get the LNP into stem cel ls in t he bone marrow. That has various appli- cations for hematologica l disorders. But t hen, of course, there are tissues that are still beyond the reach of this technolog y, such as in the pancreas or crossing the blood brain barrier. For these, there are current ly no good solutions with using LNPs. It might be that, in the end, [the industr y] would need a totally different delivery technology. There has been much work going on to test a l l k inds of polymers over the years, but so far, none of them has given a big improvement or are even as potent as LNPs, so the way it looks today, I would place my bet on the LNPs.■ Stefaan De Koker, Vice-President Technology and Innovation, etherna A Closer Look at mRNA in Oncology and Vaccines Based off the success of the messenger RNA (mRNA)-based COVID-19 vaccines, the biopharma industry is responding with enthusiasm and intense focus on the development of mRNA-based therapeutics for diseases. An area of particular challenge is the delivery of the mRNA therapeutic in vivo. Here, Stefaan De Koker, vice-president of Technology and Innovation, etherna, goes into more detail about developing mRNA-based therapeutics for oncology and vaccines, and discusses the practical application of lipid nanoparticles toward that goal. Pharmaceutical Technology presents the Drug Solutions podcast, where the editors chat with industry experts from across the pharmaceutical and biopharmaceutical supply chain. Join us as experts share insights into your biggest questions—from the technologies, to strategies, to regulations related to the development and manufacture of drug products. For more podcast episodes, visit our website! SCAN ME