CRISPR (clustered regularly interspaced short palindromic repeat) is an adaptive immune system that provides protection against mobile genetic elements (viruses, transposable elements and conjugative plasmids). CRISPR-Cas systems act in three stages: (1) adaptation, (2) CRISPR RNA (crRNA) biogenesis and (3) interference. The adaptation stage involves insertion of a new spacer, derived from the invading genetic material, into the CRISPR array (i.e., sequences complementary to antecedent mobile elements, and target invading nucleic acids). In the second stage, the CRISPR array is transcribed as a precursor CRISPR RNA (pre-crRNA), which is then processed into mature crRNAs containing a part of the repeat and the spacer. In the final stage, interference, a complex formed by the mature crRNA with single or multiple Cas proteins, recognizes spacer-complementary sequences (protospacers) on the invading nucleic acids and mediates their cleavage. This leads subsequently to the destruction of the foreign genetic material (endonuclease activity). In some cases, a short protospacer adjacent motif (PAM) sequence located next to the targeted protospacer is necessary for both adaptation and interference stages. he protospacer adjacent motif (PAM) in the CRISPR repeat sequences to help distinguish self versus non-self, as targets within the bacterial CRISPR locus do not have PAMs. PAM recognition is also required for catalytic activity. In type II CRISPR systems correct processing of pre-crRNA requires a trans-encoded small RNA (tracrRNA), endogenous ribonuclease 3 (rnc) and this protein. The tracrRNA serves as a guide for ribonuclease 3-aided processing of pre-crRNA. Cas9 is inactive in the absence of the 2 guide RNAs (gRNA).