Establishing Analytical Methods For mRNA-Based Therapies

Nucleic acid-based modalities, such as pDNA and mRNA vaccines, offer diverse options for addressing unmet medical needs. The efficacy of the SARS-CoV-2 vaccines has demonstrated the versatility of mRNA as well as its potential for rapid market availability. Given the complexity of this emerging modality, rigorous characterization and testing are required to ensure safe and effective mRNA drug products.

mRNA modalities can be manufactured using a pDNA template or in vitro transcription and must be formulated into the final drug product for targeted delivery, often by encapsulating the mRNA into a lipid nanoparticle (LNP). A comprehensive set of analytical tests are required to ensure the quality and safety of these nucleic acid assets.

Both the RNA drug substance and the formulated drug product should be subjected to stringent testing prior to release. Here, we provide a detailed description of assays for sequence identification and LNP compositional, two critical quality attributes of mRNA-LNP products, that support the development of safe and effective mRNA therapies.