(438d) Continuous Manufacturing of mRNA-Loaded Lipid Nanoparticles: Structural and Morphological Insights

Lipid nanoparticles (LNPs) have emerged as a leading platform for delivering nucleic acid-based therapeutics ¹, including mRNA vaccines. These self-assembled, core-shell structures encapsulate nucleic acids within a lipid matrix, exhibiting diverse structural and morphological features that influence their stability and efficacy ².

LNPs are continuously manufactured by rapidly mixing a lipid-ethanol stream with an aqueous nucleic acid solution using microfluidic chips or impinging jet mixers. Critical process parameters—including flow rates and stream compositions—define a vast design space and directly impact LNP morphology and structure. Understanding the relationship between process conditions and LNP structure is essential for optimizing manufacturing and ensuring product consistency. This study examines the structural and morphological diversity of LNPs in continuous manufacturing.

¹ Hamilton, A. G., Swingle, K. L. & Mitchell, M. J. Biotechnology: Overcoming biological barriers to nucleic

acid delivery using lipid nanoparticles. PLOS Biology 21, e3002105 (2023).

² Udepurkar, A., Devos C., Sagmeister P., Destro F., Inguva, P., Ahmadi, S., Boulais E., Quan Y., Braatz R.D., Myerson, A.S. Structure and Morphology of Lipid Nanoparticles for Nucleic Acid Drug Delivery: A Review. Under Review