A Native Mass Spectrometry-Based Assay for Rapid Assessment of the Empty:Full Capsid Ratio in Adeno-Associated Virus Gene Therapy Products

Adeno-associated virus (AAV)-based gene therapy is a rapidly developing field, requiring analytical methods for detailed product characterization. One important quality attribute of AAV products that requires monitoring the amount residual empty capsids following downstream processing. Traditionally, and full particles are quantified via ultracentrifugation as well anion exchange chromatography using ultraviolet or fluorescence detection. Here, we present native mass spectrometry-based approach to assess ratio AAV-capsids without need excessive sample preparation. We report rapid determination relative in AAV5 AAV8 samples. The results correlate with more conventional analysis strategies, demonstrating potential spectrometry characterization viral particles.