We first targeted a 2.5-kb CAG-EGFP transgene into three identified safe harbor loci including CCR5, AAVS1, and TRAC, and three inherited disease-related genes including WAS (associated with Wiskott-Aldrich Syndrome and Thrombocytopenia 1)24, HBB (associated with Beta-Thalassemia and Sickle Cell Anemia)25,26 and IL2RG (associated with X-linked severe combined immunodeficiency)27 in K562 cells, a myeloid tumor cell line. Here, TRAC is linked to T-B+ severe combined immunodeficiency due to gamma chain deficiency.