Discovery of genomic safe harbor sites (SHS) is fundamental for multiple transgene 22 integrations, such as reporter genes, chimeric antigen receptors (CAR), and safety switches, 23 which are required for safe cell products for regenerative cell therapies and immunotherapies. 24 Here we identified and characterized potential SHS in human cells. Using the CRISPR25 MAD7 system, we integrated transgenes at these sites in iPSC, primary T and NK cells, and 26 Jurkat cell line, and demonstrated efficient and stable expression at these loci. Subsequently, we validated the differentiation potential of engineered iPSC towards CD34+ 27 hematopoietic 28 stem and progenitor cells (HSPC), lymphoid progenitors (LPC), and natural killer (NK) cells, 29 and showed that transgene expression was perpetuated in these lineages. Finally, we 30 demonstrated that engineered iPSC-derived NK cells retained expression of a non-virally 31 integrated anti-CD19 CAR, suggesting that several of the investigated SHS can be used to 32 engineer cells for adoptive immunotherapies.