posted on 2021-09-14, 12:36authored byLisa Strasser, Tomos E. Morgan, Felipe Guapo, Florian Füssl, Daniel Forsey, Ian Anderson, Jonathan Bones
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
is the amount of residual empty capsids following downstream processing.
Traditionally, empty and full particles are quantified via analytical
ultracentrifugation as well as anion exchange chromatography using
ultraviolet or fluorescence detection. Here, we present a native mass
spectrometry-based approach to assess the ratio of empty to full AAV-capsids
without the need for excessive sample preparation. We report the rapid
determination of the relative amount of empty capsids in AAV5 and
AAV8 samples. The results correlate well with more conventional analysis
strategies, demonstrating the potential of native mass spectrometry
for the characterization of viral particles.