ArticleAnalytical chemistry2025
Ion Mobility Gas-Phase Separation Enhances Top-Down Mass Spectrometry of Heavily Modified Guide RNA.
Article in Analytical chemistry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Rapid Exonuclease-Based De Novo Sequencing Strategy for Long Oligonucleotides via Liquid-Phase Ion Trap Coupled With Mass Spectrometry.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Review
- Activation of Oligonucleotide Polyanions Using Collisions, Electrons and Photons in a timsOmni Platform.Journal of the American Society for Mass Spectrometry · 2026Article
- Increasing Oligonucleotide Sequencing Information and Throughput with Ion Mobility Spectrometry-Mass Spectrometry.Journal of the American Society for Mass Spectrometry · 2025Article
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Authors and funding
5 authors.
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Abstract
As gene editing technologies enter the clinic, state-of-the-art characterization methods have been developed in parallel to assess the components of these paradigm-shifting medicines. One such component, the guide RNA (gRNA) element of CRISPR-based drugs, is a large synthetic heavily modified oligonucleotide that programs for the desired gene edit. Conventional oligonucleotide sequencing technologies can inform gRNA composition, but these methods may not completely capture the chemical modifications that are introduced during synthesis. Circumventing these challenges, mass spectrometry has demonstrated use in oligonucleotide analyses and has been combined here with ion mobility to deepen its characterization power. The use of ion mobility enabled us to perform gas-phase separation of the fragment ions produced by top-down mass spectrometry, yielding a significant increase in fragment identifications for a highly modified 100-mer gRNA by uncovering high-confidence assignments for heavily modified regions and for the important spacer region. Furthermore, the high-confidence fragment assignments empowered simultaneous
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