Mass Spec 2021 Keynote: Albert Heck, Utrecht University

A Detailed Look at Antibodies, Plasma Proteins, Viruses, and Gene-Delivery by High-Resolution Native Mass Spectrometry

Modern biopharmaceutical products, but also most plasma proteins, exhibit extensive structural micro-heterogeneity due to co-occurring post-translational modifications. These modifications affect their functionality and thus need to be characterized in detail. We use high-resolution native mass spectrometry, often combined with glycoproteomics and top- and middle-down proteomics, to analyze this micro-heterogeneity. Taking mAbs, erythropoietin and plasma proteins as model systems, we demonstrate an all-inclusive quantitative profiling of glycoproteins. We demonstrate the usage of a biosimilarity score to quantitatively assess structural similarities.

Moreover, by extending the mass range of Orbitrap mass analyzers we have expanded the reach of native mass spectrometry to higher molecular weight compounds, such as IgG hexamers, endogenous viruses and gene delivery vectors such as the adenovirus. I will describe the latest developments, including Orbitrap based single particle charge detection mass spectrometry, and how that can be used to assess the quality and purity of this next generation of biopharmaceutical products.