Abstract: Present application relates to a strategy for compensating for transesterification degradation of lipid-encapsulated SARS-CoV-2 mRNA vaccine, in liquid formulations for high-volume distribution. This involves determining the rate of degradation of the encapsulated RNA and calculating an appropriate overage relative to the intended dose. Alternatively, a higher dose of the RNA may be administered to compensate for loss of effective RNA or the RNA may be formulated in higher purity in anticipation of degradation. The strategy provides a balance between supplying effective and safe products and the need for costly manufacturing processes or transportation hurdles, such as cold-chain supply.

Abstract: Present application relates to a strategy for compensating for transesterification degradation of lipid-encapsulated RNA, such as mRNA-LNP, in liquid formulations for high-volume distribution. This involves determining the rate of degradation of the encapsulated RNA and calculating an appropriate overage relative to the intended dose. Alternatively, a higher dose of the RNA may be administered to compensate for loss of effective RNA or the RNA may be formulated in higher purity in anticipation of degradation. The strategy provides a balance between supplying effective and safe products and the need for costly manufacturing processes or transportation hurdles, such as cold-chain supply.