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Vast numbers of new and mysterious ncRNAs continue to be discovered across the tree of life. Although many key questions remain to be answered, nevertheless there are grounds for great optimism for the relevance of ncRNAs to biology and medicine. Powerful new tools are being refined to detect and manipulate ncRNAs with confidence and accuracy, including chemical structure probing, spatially-resolved sequencing, and of course CRISPR-based technologies. At the same time, rapid strides are being made in translating these findings to the clinic, not least thanks to oligonucleotide drugs.