Applications of SV-AUC during the development of lipid nanoparticles and viral vectors

Analytical ultracentrifugation is an established method during the development of therapeutic proteins and antibodies and contributes supporting information regarding the size, oligomerization state and impurity contents of oligomeric forms and aggregates. While the precision of orthogonal methods, such as high performance size exclusion chromatography (HP-SEC) may be higher, the ability of sedimentation velocity analytical ultracentrifugation (SV-AUC) to perform the analysis in the absence of any potentially interfering matrices leads to high confidence in the accuracy of the results, as information on the solutes will not be affected by potentially specific matrix interactions. This is particularly important during the characterization of lipid nanoparticles (LNPs) as well as viral vectors, where the hydrophobic chemical nature of LNPs and the size of both particulate API types may lead to solute-specific matrix interactions. We present case studies during the development of LNPs, adeno associated virus (AAV)-based therapeutics and lentiviral vectors, all of which are strongly supporting SV-AUC as a standard method during the development and GMP-compliant batch release of novel vaccines as well as viral vector-based advanced therapy medicinal products (ATMPs).