Simultaneous Quantification of RNA and Antibodies in Lipid Nanoparticles by Scatter-Free Absorption Spectroscopy

Kirsty Smith – Head of Applications, Marama Labs; Eric Le Ru – Chief Science Officer, Marama Labs; Moritz Beck-Broichsitter – Head of LS-SC-UYTF Group, Merck Life Science KGaA; Eleni Samaridou – Head of Early-stage Formulation Development and Process Design, Merck Life Science KGaA; María José Alonso – Professor and Group Leader, University of Santiago de Compostela; Brendan Darby – Chief Executive Officer, Marama Labs; Johanna Simon – Head of Formulation Discovery & Analytical Characterization, Merck Life Science KGaA

Introduction: The development of targeted RNA-loaded lipid nanoparticles (tLNP) for cell-specific delivery is a major focus in nanomedicine, with antibody (Ab) functionalization as a leading strategy. However, accurate Ab quantification on the surface of LNP remains challenging. Conventional fluorescence-based assays (e.g., RiboGreen™ and BCA) require separate workflows and may be affected by LNP disruption and lipid interference, while UV/Vis spectroscopy is unsuitable due to LNP’s light scattering. This work introduces scatter-free absorption (SFA) spectroscopy for simultaneous and precise RNA and Ab quantification in LNP (1,2).