Extraction of mRNA from LNPs is required to control the quality of mRNA in final drug products.

Different methods have been compared to extract mRNA from LNPs.

Advantages and disadvantages of the different methods are highlighted.

Selection should be based on the method's efficiency, duration, ease of use, automation level, and use of toxic reagents.

Messenger RiboNucleic Acid (mRNA) vaccines have recently shown considerable promises for both prophylactic and therapeutic vaccines. These vaccines do not carry an antigen but the information for producing it using the cell machinery, turning the human body into an antigen factory. However, mRNA is an unstable molecule, susceptible to physical, chemical and enzymatic degradation by exo- and endonucleases. If the mRNA is degraded, it can no longer be translated correctly into the antigen of interest and the vaccine lose its efficacy. To protect from nucleases degradation and allow it to get into the cells, mRNA can be encapsulated in lipid nanoparticles (LNPs). As part of the manufacturing process, the quality of the mRNAs should be controlled before the encapsulation (at the drug substance stage) as well as after formulation on the final vaccine product (at the drug product stage). Therefore, it is necessary to be able to extract the mRNA from the LNPs, that is to deformulate the final vaccine product. In this work, different deformulation methods have been compared: spin column extraction, magnetic particle extraction, organic extraction, and direct disruption. Advantages and disadvantages of each of these methods are highlighted.

mRNA

Deformulation

Extraction

Lipid nanoparticle

Integrity

Data will be made available on request.

© 2023 The Author(s). Published by Elsevier B.V.