RNA plays important and diverse roles in biology, but molecular tools to manipulate and measure RNA are limited. We demonstrate that RNA- targeting CRISPR effector Cas13 can be engineered for mammalian cell RNA knockdown, binding, and RNA editing. Cas13 can be heterologously expressed in mammalian and plant cells for targeted knockdown of either reporter or endogenous transcripts, targeted RNA binding for transcript imaging, and programmable RNA editing. We demonstrate that directly evolved RNA editors are highly active and specific for temporally modulating signaling pathways in diverse cell types, including non-dividing cells such as neurons. We also combine Cas13a with isothermal amplification to establish a CRISPR-based diagnostic (CRISPR-Dx), providing rapid DNA or RNA detection with attomolar sensitivity and single-base mismatch specificity. We use this Cas13a-based molecular detection platform, termed SHERLOCK, to detect specific strains of Zika and Dengue virus, distinguish pathogenic bacteria, genotype human DNA, and identify cell-free tumor DNA mutations. Our results establish CRISPR-Cas13 as a flexible platform for RNA targeting with wide applicability for studying RNA or therapeutics.
