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32 Pharmaceutical Technology ® The Real Message Behind Commercial mRNA Products April eBook 2023 PharmTech.com Drug Delivery process yields (again, making the material cheaper). Table I illustrates some CQAs and t y pical values, which are lower than the limit of quantification. LNP delivery of mRNA L N P s a s u s e d i n t he COV I D -19 v a c c i ne s , a n d many prophylactic vaccines under development, are the most advanced delivery vehicle for mRNA. LNPs are composed of four lipid classes, each with a functional role: • ionizable lipid: mRNA complexation, endosomal escape • helper phospholipid: structure, endosomal escape • sterol: structure • PEGylated lipid: stability. Variables affecting LNP properties and biological activity include: • lipid chemistries • lipid ratio • mRNA to lipid ratio • manufacturing process. Figure 6 shows how a n L NP d iscover y engi ne id e n t i f ie s pr opr ie t a r y or g a n-s p e c i f ic L N P s b y s ystemat ica l ly opt i m izi ng t he four l ipid compo- nents. Screening an interna l librar y of ionizable l ipid s ha s enabled t he development of L N Ps for Proprietary Lipid Library (e.g., ionizable lipid backbone) Co-formulation Lipids (e.g, cholesterol, DOPE, Pegylated Lipids) Future goal: Functional components (e.g., targeting moieties) Optimization of LNP composition via DOE (Design of Experiment) and Bayesian Regression Modelling Proprietary LNP formulations optimized for organ-specific biodistribution to enable targeting of mRNA for specific applications FIGURE 6. etherna's LNP Discovery Engine. TABLE II. Tissue targeted LNPs produced by etherna's discovery engine LNP Administration Tissue Therapeutic area IV-LNP1 Intravenous Spleen (liver) Immuno-oncology iTu-LNP1 Intratumoral Tumor Immuno-oncology IV-LNP2 Intravenous Spleen, Liver Autoimmune disease IM-LNP1 Intramuscular Muscle, lymph node Infectious disease