 This paper discusses the development of a novel imaging based in vitro assay to measure the potency of lipid nanoparticle, LPN, encapsulated messenger RNA, mRNA, vaccine candidates. The assay was designed to provide a wide dose response curve and dynamic range, while also being sensitive to the various properties of the LPNs, such as polyethylene glycolipid, PG lipid, composition, mRNA mass, and LPN size. Several biologically relevant cell lines were screened and optimized to ensure the assay's suitability for measuring mRNA vaccine potency. This article was authored by Nisurg Patel, Zack Davis, Carl Hoffman, and others.