CRISPR–Cas immune systems and genome engineering

Abstract The famed physicist-turned-biologist, Max Delbruck, once remarked, for physicists, “the field of bacterial viruses is a fine playground for serious children who ask ambitious questions.” Early discoveries in that playground helped establish molecular genetics, and half a century later, biologists delving into the same field have ushered in the era of precision genome engineering. The focus has of course shifted—from bacterial viruses and their mechanisms of infection, to the bacterial hosts and their mechanisms of immunity—but it is the very same evolutionary arms race that continues to awe and inspire researchers worldwide. In this chapter, we explore the remarkable diversity of clustered regularly interspaced short palindromic repeats (CRISPR)–Cas adaptive immune systems, describe the molecular components that mediate nucleic acid targeting, and outline the use of these RNA-guided machines for biotechnology applications and studies of neurological disease. CRISPR–Cas research has yielded far more than just Cas9-based genome-editing tools, and the wide-reaching, innovative impacts of this fascinating biological playground are sure to be felt for years to come. This chapter has been adapted from a review previously published in The CRISPR Journal.