The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 system is the latest RNA-guided, endonuclease tool in genome editing which allows for very specific genomic disruption and replacement. ;;The saCas9 Null Mutant Protein is created by mutating both cleavage domains of the wild type saCas9. Such a saCas9 protein retains its ability to bind to genomic DNA through sgRNA:genomic DNA base pairing, however, the saCas9 Null Mutant does not induce cleavage. Therefore, this protein can provide a useful negative control for CRISPR experiments. In addition, binding of the Null Mutant can act as a roadblock to hinder transcription, thus offering a useful tool to achieve reversible knock-down of gene expression.;;The Cas9 nuclease from the bacteria Staphylococcus aureus, abbreviated saCas9, is gaining popularity as an alternative to spCas9 due to its relatively smaller size. The saCas9 PAM sequence is 5’-NNGRRN (preferably 5’-NNGRRT).