Recently, RNA-guided Cas nucleases have been engineered for rapid and precise genetic manipulation in a variety of organisms, including many eukaryotic cells and diverse bacterial species . Through base pairing with a genomic sequence adjacent to a protospacer adjacent motif (PAM), the Cas/gRNA complexes can specifically bind to the target genomic site and generate a double-stranded DNA break (DSB). With the assistance of the cellular homology-directed repair (HDR) pathway or the nonhomologous end joining (NHEJ) pathway, precise and non-precise genetic manipulations can be readily achieved, respectively. Moreover, the CRISPR-Cas systems can be further engineered to be transcription inhibition (CRISPRi) systems for direct gene knockdown without relying on cellular DNA repair mechanisms . In M.