Mass spectrometry in gene therapy: Challenges and opportunities for AAV analysis

The characterization of adeno-associated virus (AAV)-based gene therapy products represents significant challenges owing to their extremely large molecular sizes, structural complexity and heterogeneity, and limited sample amounts. Mass spectrometry (MS) is one of the key analytical tools that can overcome these challenges and serve as an important technique for the analysis of multiple attributes. In this review, the current methodologies and emerging trends in MS analysis of AAV gene therapy products are presented, highlighting their advantages and unique capabilities in addressing key issues encountered in intact AAV vector analysis, capsid viral protein characterization and impurity analysis.