In the last 17 years, I developed gene editing tools to improve cancer immunotherapy or promote safer applications of human hematopoietic stem cell (HSC) gene therapy. I pioneered this field since when the first gene editing enzymes were shown to be potentially useful for therapeutic purposes. In 2012, I published a break-through work where we demonstrated for the first time the possibility to genetically inactivate the T cell receptor in primary T cells for improving safety/efficacy of cancer adoptive immunotherapies. This innovative approach is now widely used in immunotherapy field for generating allo-compatible T cells or to express CAR genes under the TCR promoter. In 2014, I developed the first protocol that allows targeted transgene integration in human HSC capable of long-term multilineage repopulation. My current efforts are aimed to move these advanced genetic engineering strategies towards an effective therapeutic treatment for inherited and acquired hematologic diseases.