Mass Spectrometry of Nucleic Acids

<jats:title>Abstract</jats:title> <jats:p>Over the years, scientists and researchers have been increasing their knowledge about oligonucleotides and nucleic acids by studying their properties, characteristics, modifications, and sequences. Characterizing nucleic acids using mass spectrometry has led to very interesting research and discovery. Mass spectrometry is an accurate, rapid, and sensitive tool that has been used to analyze shorter nucleosides as well as long oligonucleotides (&gt;100 nts long). Sequencing of oligonucleotides and nucleic acids has been improved due to better instrumentation as well as more advanced data analysis software coming online. This approach has impacted clinical diagnostics, forensics, the study of noncovalent complexes, misincorporation analysis of translesion DNA synthesis products, detection and mapping of DNA lesions, RNA therapeutics, and detection and characterization of DNA–protein cross‐links. This article reviews some fundamental properties of nucleic acids, provides an in‐depth look at how liquid chromatography coupled with electrospray ionization mass spectrometry is now a widely used tool to analyze nucleic acids of varying size, chemical properties, and biological functions, describes a variety of approaches for using mass spectrometry to obtain sequence information about oligonucleotides and nucleic acids, and provides a glimpse into various applications that benefit from the use of this approach.</jats:p>