(334b) mRNA Formulation Development: Looking Beyond the Pandemic

The approval of the two COVID vaccines, SpikeVax® (Moderna) and Comirnaty® (BioNTech/Pfizer), has propelled mRNA-lipid nanoparticle (LNP) technology to the forefront of the vaccine and therapeutic industry. Given the wide application of mRNA technology, there has been a tremendous amount of ongoing work in many different areas such as protein replacement therapy, oncology, gene editing, and other treatments of genetic diseases. In this work, different examples of mRNA formulations for vaccines via local or systemic delivery will be presented. Representative examples of innovations in lipid nanoparticle design covering novel ionizable lipids, PEG lipids, helper lipids, sterol analogues, and excipients will be shared.

Improving thermostability of mRNA products for storage at refrigerated conditions is critical to expand the applications beyond the pandemic situation and make global use possible. Examples of preliminary data showing improved thermostability across different dose forms will be shared along with the next steps for future development of the mRNA platform.

A representative example of PEG lipid screening and formulation optimization will also be presented. PEG lipid, among other LNP components, prevents particle aggregation in the vial and opsonization in the blood. In SpikeVax and Comirnaty, PEG 2000 with dimyristoyl glycerol or ditetradecylacetamide is used to stabilize LNPs for ionizable lipids SM102 and ALC315, respectively. In this presentation, our work to screen PEG lipids with different structural features and optimize formulation compositions to enhance protein production and immunogenicity in vivo, improve thermostability and understand structure-activity relation will be discussed.

This work was funded by Sanofi.

Both authors are Sanofi employees and may hold shares and/or stock options in the company.