Schematic representation of the CRISPR-Cas adaptive immunity. (a) Upon viral infection, parts of invading nucleic acids are internalized into the CRISPR genetic array that subsequently transcribes and matures into a guide RNA complex containing a CRISPR RNA (crRNA) and trans-CRISPR RNA (tracr-RNA). (1) The Cas9 protein binds the guide RNA and uses its sequence to recognize complementary DNA sequences. Site-specific recognition of the viral DNA is preceded by the binding of a short Protospacer Adjacent Motif (PAM), which enables the selection across the genome. (b) Three-dimensional structure of the Streptococcus pyogenes CRISPR-Cas9 (SpCas9) complex with a guide RNA and DNA (PDB code: 4UN3).10 Cas9 is shown in molecular surface, highlighting individual domains in different colors. The RNA (yellow), target DNA (TS, cyan), and nontarget DNA (NTS, violet) are shown as ribbons