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The structure, dynamics, and interactions of nucleic acids, in particular DNAs, sensitively respond to a broad range of environmental factors, many of them being natively present in the intracellular space. In-cell NMR is a tailored adaptation of conventional high-resolution nuclear magnetic resonance spectroscopy that permits characterization of stereochemical features of nucleic acids directly in living cells. Here we review recent advances and applications of in-cell NMR to nucleic acids. The limitations of this method as well as the general considerations, comprising of critical factors to be accounted for during the planning of in-cell NMR experiments, as well as during the interpretation of in-cell NMR data, are discussed.

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