Kim, Y.-K. et al. Nat. Struct. Mol. Biol. 20, 1458–1464 (2013).

microRNAs are important regulators that degrade mRNAs or prevent their translation and thereby have key roles in development and several diseases. Various methods to inhibit microRNAs exist and allow one to study their function, but Kim et al. took a departure from previous piecemeal approaches and designed tools to efficiently knock out 274 of the 1,600 human microRNA loci. The researchers produced a library of 540 pairs of transcription activator-like effector nucleases (TALENs) to delete genes for important human microRNAs and, as a proof of principle, generated single and double knockout cell lines for miR-141 and miR-200c in only a few weeks. The cells showed the expected upregulation of mRNAs containing motifs of the deleted microRNAs.