Figure 1 Adaptive immune system of bacteria and archaea Figure 1 | Adaptive immune system of bacteria and archaea. CRISPR-associated (Cas) genes (cas) (blue arrows) encode proteins required for new spacer sequence acquisition, CRISPR RNA (crRNA) biogenesis and target interference. Step 1. Acquisition. Unique sequences (protospacers) are acquired from invading viruses and inserted into the host genome, separated by partially palindromic repeats (Repeat). Adjacent to protospacers are short sequences called protospacer adjacent motifs (PAMs). Step 2. crRNA biogenesis. In response to viral invasion, long CRISPR transcripts (pre-crRNA) are processed into short crRNAs that guide Cas proteins to invading DNA through complementary base-pairing. Step 3. Target interference. Cas nucleases initiate double-strand breaks in the DNA at the target site. Permission obtained from Annual Reviews © Sorek, R. et al. Annu. Rev. Biochem. 82, 237–266 (2013). Permission obtained from Annual Reviews © Sorek, R. et al. Annu. Rev. Biochem. 82, 237–266 (2013). Gibson, G. J. & Yang, M. (2017) What rheumatologists need to know about CRISPR/Cas9 Nat. Rev. Rheumatol. doi:10.1038/nrrheum.2017.6