Genome editing provides a mechanism to precisely change the DNA sequence of cells with single nucleotide precision. We have developed a highly efficient platform to modify multiple types of human stem cells, including hematopoietic stem cells and pluripotent stem cells, with high efficiency using a combination of CRISPR/Cas9 and AAV6. I will discuss our progress in applying this platform to several different genetic diseases of the blood and immune system including sickle cell disease and severe combined immunodeficiency. In addition, I will discuss our optimized protocols to generate precisely modified human pluritpotent stem cells.