A potential cycle of B cell–mediated therapies including an ex vivo genome edition step. B cells are extracted from the patient, gene-edited using CRISPR/Cas9 technology, and infused back to the patient. (A) Two cleavages can lead to deletion of the C_µ gene and class switch recombination from IgM to IgG.⁷⁷  One cleavage between the hinge region and the constant region allows the generation of a Fab′ fragment.⁷⁷  (B) Insertion of a cassette encoding the VH chain and a light chain linked with a tag-linker leads to expression of an sc immunoglobulin with modified specificity.⁷⁹  Hartweger et al⁸⁰  described a similar strategy with an additional stop codon to disrupt expression of the endogenous immunoglobulin. iE, enhancer; I, intervening; S, switch; C, constant.