Regulation of γ globin production in humans. (A) At birth, LRF/ZBTB7A and BCL11A bind at cis regulatory regions at HBG (−200 bp and −115 bp from the promoter) to repress γ globin production. Combined CRISPR-Cas9 editing of the BCL11A enhancer, and LRF/ZBTB7A or BCL11A binding sites, to derepress γ globin production. (B) In vivo transduction of human CD34⁺ cells, from patients with β-thalassemia engrafted in NSGW mice, with a dual sgRNA–containing adenoviral vector.