Toward routine utilisation of native mass spectrometry as an enabler of contemporary drug development

As therapeutic modalities increasingly diversify, the need for biophysical tools for routine characterisation of the underlying biomolecular targets and their noncovalent interactions is growing. In this Opinion article we discuss the role of native mass spectrometry (nMS), a mass spectrometry technique where the intact biomolecule and its noncovalent interactions are preserved during the analysis, to gain important insights to guide drug discovery and development. We conclude that nMS is one of the most powerful technologies available with potential to rapidly advance multiple stages of therapeutic discovery and development, yet it is arguably underutilised. Specifically, we highlight how nMS may progress research for contemporary therapeutic modalities including those implicated in targeted protein degradation, fragment-based drug discovery and mRNA therapies.