Overcoming Low Throughout Testing Issues of AAV Using SEC-MALS

Adeno associated virus (AAV) capsids are a leading modality for in vivo gene delivery. Complete and precise characterization of capsid particles, including capsid and vector genome concentration, is necessary to safely and efficaciously dose patients. Size exclusion chromatography (SEC) coupled to multiangle light scattering (MALS) offers a straightforward approach to comprehensively characterize AAV capsids, including, but not limited to aggregation profile, size-distribution, capsid content, capsid molar mass, encapsidated DNA molar mass, and total capsid and vector genome titer. Currently, multiple techniques are required to generate this information, with varying accuracy and precision. SEC-MALS can leverage intrinsic physical properties of the capsids and encapsidated DNA to quantify multiple AAV attributes in one 20-min run with minimal sample manipulation, high accuracy, and high precision. As such, SEC-MALS is a powerful tool for product development and process analytics in future gene therapy programs.