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Schematic representation of the iCROP-modified (d)Cas9 protein. dCas9 or Cas9 protein bearing the HRV protease at the N-terminus and the cognate CS at position R535 is fragmented into two inactive parts, unless the protease inhibitor is present. In the presence of inhibitor, (i) active dCas9 associates with a target sgRNA fused to an MS2 loop, which co-localizes the MCP protein fused to a transcriptional activation domain in the promoter region of the target gene, thereby activating transcription; and (ii) active Cas9 associates with a target sgRNA introducing mutations in a target genomic locus.

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