VIF World 2026

Listen to our talk

Speaker: Jasmina Puc, Product Manager mRNA/pDNA
Time and Date: March 12, 9:50 AM
Title: Monolith-Enabled RNA–LNP Manufacturing: Higher Recovery, Tighter Size Distribution, and Clear Quality Readouts

Location: Shanghai, China

Join us!

Abstract:

Lipid nanoparticle (LNP) therapeutics field is looking for additional, orthogonal analytics and an efficient alternative to buffer exchange by tangential flow filtration (TFF) or dialysis. In this talk I will present an end-to-end, monolith-enabled workflow from plasmid DNA (pDNA) to RNA–LNP drug product, with a focus on simple, robust process control and clear product characterization.
GMP-compliant pDNA is produced using the Alkalizator system and purified on monolithic columns to obtain high-purity linear pDNA. In vitro transcription (IVT) utilizes the pDNA template to generate mRNA, which is subsequently captured and polished with a modular monolith toolbox adaptable to different RNA formats. This creates a clean, stable RNA drug substance, ready for LNP encapsulation and formulation.
After encapsulation and neutralization, LNPs are processed on CIMmultus® OH monoliths under optimized kosmotropic conditions. In a single step, the column concentrates the sample, removes ethanol, exchanges the buffer, and clears non-encapsulated RNA and residual lipids. The laminar, low-shear flow of CIMmultus columns preserves particle integrity and allows fractionation when needed. Compared with TFF or dialysis, this approach delivers higher total mRNA recovery, a narrower particle size distribution, and higher functional activity as measured by a cell-based assay.
Process and product analytics are provided by the PATfix® platforms. The PATfix LNP Switcher combines two-dimensional monolithic chromatography (OH and SDVB) with UV, multi-angle light scattering, and fluorescence detection. It quantifies key quality attributes, including encapsulation efficiency, particle size and heterogeneity, nucleic acid integrity, and nucleic acid–lipid adducts. Our newest ion-exchange analytical method further separates intact particle subpopulations, distinguishing targeted (ligand-decorated) LNPs from non-targeted particles, a key quality attribute in development of tLNPs
By integrating monolithic purification with orthogonal PATfix analytics, this workflow establishes a robust CMC control strategy and a scalable chromatographic alternative to filtration- or dialysis-based buffer exchange. The platform supports consistent quality for single- and multi-cargo LNPs used in CAR-T, CRISPR, and vaccine applications.