Issue link: https://www.e-digitaleditions.com/i/1497323
4 Pharmaceutical Technology ® The Real Message Behind Commercial mRNA Products April eBook 2023 PharmTech.com T o re-engineer messenger RNA (mRNA) to be a silent and efficient way of delivering protein to cells will be the key to moving it beyond its current vaccine home. I asked Stephen Rapecki, director of Experimental Therapeutics, UCB, what that might look like going forward, for an article I wrote in January 2023 (1). Rapecki replied, "This starts with how we deliver the mRNA. Current nanoscale particles (referred to as lipid nanoparticles or LNPs) needed to deliver mRNA to the cytoplasm of cells are in themselves highly immunogenic. So, assuming less immunogenic forms of LNPs are developed the second challenge is delivering mRNA to its chosen cell or organ. mRNA vaccines administered subcutaneously most likely deliver their immunogenic payload to antigen presenting cells at the site of injection and to draining lymph nodes. This allows small and targeted doses of vaccine to be amplified as the immune reaction is the intended outcome not the production of the protein per se." So, moving forward into other therapeutic indications requires re-wiring our thinking with regard to how to deploy mRNA as an actual tool. And this then raises the level of challenge of technical and manufacturing difficulty, as Rapecki goes on to point out. "To deliver a protein to correct a condition or replace a defective version of a protein will require much larger amounts than for immunization perhaps by factors of up to a thousand. Such manufacturing challenges though are not insurmountable given the exciting opportunities mRNA offers drug hunters" (1). In October 2022, I helped organize and run a high caliber event in San Diego, Calif. for "mRNA Day" with TriLink BioTechnologies to discuss common manufacturing, supply, and regulatory challenges relating to mRNA as a platform. Interspersed between conversation around the high cost of required enzymes, the need to be serious about how to manage DNA as a starting medium, and cut off points for potency assays, we devoted significant time and energy to discussing what benefits might accrue from establishing a supplier-developer consortium, especially to set up systems for correct and agreed upon standards and regulatory streamlining. During an hour-and-a-half panel, we added the idea of a central railway station system for supply shortage oversight, easy access to best new publications, and centralized advocacy for staff recruitment through university and technical college classes, alongside staff training best practices. I concluded by observing that mRNA felt like the field of proteomics 20 years ago (I co-founded HUPO with Ian Humphrey-Smith), ready to con- solidate gains while helping to lay down tracks for future destinations and activities. On April 5, 2023 at the law firm of Leavitt Partners in Washington, DC, key opinion leaders in the mRNA business and scientific community picked up this dialogue (senior leadership from 10 pharmaceutical, 15 biotechnology, six academic, three US government, six contract development and manufacturing organizations, and three service providers) and gathered as a working group to discuss what building this new infrastructure might entail, and the skills and experience that might be required from a potential "Alliance for mRNA Medicine." This was an open discussion partially framed by a shocking headline interceding in FDA approvals which stated, "physicians say an Idaho house bill that would criminalize administering mRNA vaccines is an attack on the medical profession—even if it doesn't become law" (2). I might add this bill is also a blatant attack on common sense and propels the mind back to the early days of the pandemic where sound advice and reliable pharmaceutical judgments were mixed in with conspiracy theories and medieval superstition. "It's one thing if you've got wild conspiracy theories on social media and the Internet; it's quite another when elected officials set out to enact those policies," said Lawrence Gostin, who directs the O'Neill Institute for National and Global Health Law as well as the World Health Organization Collaborating Center on National and Global Health Law (2). There is a real need for both consolidation and standardization of resources in mRNA. It's not a train we necessarily all need to get onboard im- mediately, but we should know where the central train station is located, and what it connects us to. We require a central resource to not only advocate and disseminate good science policy, but a central resource that unimpeachably can be trusted at all times as a positive voice for great healthcare, honest science, and reliable advice. The enthusiasm surrounding the making of this eBook illustrates that we are quite literally still at the beginning of our mRNA journey. Let's pool resources, insights, and know-how to make that happen as robustly as possible References 1. Spivey, C. Six Approaches Making the Most Significant Impact in the Future. Pharm. Technol. 2023 47 (1). 2. Suran, M. Physicians Say an Idaho House Bill That Would Criminalize Administering mRNA Vaccines Is an Attack on the Medical Profession—Even If It Doesn't Become Law. Medical News & Perspectives, March 15, 2023. The mRNA Message from the editor Send your thoughts and story ideas to: cspivey@mjhlifesciences.com. Chris Spivey is editorial director of Pharmaceutical Technology.