The bacterial and archaeal CRISPR/Cas systems of adaptive immunity show remarkable diversity of protein composition, effector complex structure, genome locus architecture, mechanisms of adaptation, pre-crRNA processing and interference. CRISPR/Cas systems have been divided largely into two classes, 6 types and 48 subtypes 59 (summarized in Figure and Table ). Class 1 systems include Types I, III, and IV, that use multiprotein complexes to destroy foreign nucleic acids, and class 2 systems include Types II, V, and VI, that use single proteins. In this section, we provide a brief overview of natural Cas nucleases and engineered variants that have been adopted for use as therapeutics (Figure and Table ).