(A) A guide RNA recognizes a genomic sequence, and Cas9 cuts the DNA upstream of the protospacer adjacent motif (PAM) sequence. Genome editing can lead to error-prone repair (small insertions or deletions following nonhomologous end joining that usually lead to lack of expression) or to defined changes (using a template for homology-directed repair). Additional strategies can be incorporated to precisely modify specific nucleotides or to target RNA (not shown). (B) Several clinical applications for CRISPR/Cas exist or are in development. In vivo application generally requires incorporation of the editing reagents in a vector (either nonviral such as a gel or in lipid nanoparticles or recombinant virus such as adeno-associated virus, AAV). In vivo trials are ongoing to treat blindness (specifically herpes simplex virus keratitis or Leber’s congenital amaurosis) as well as HPV-driven cervical neoplasia and transthyretin amyloidosis, a rare congenital disorder that affects multiple organs due to amyloid deposits. Ex vivo applications include diagnostic applications, such as for SARS-CoV-2 infection, as well as clinical therapies based on CRISPR/Cas modification of cells, which are then used to treat patients. Cell-based therapies to date include applications in hematologic disorders and malignancies, renal cell carcinoma, and metastatic gastrointestinal cancers.