The first attempts at hematopoietic stem cell–based gene therapy (HSC-GT) were reported >25 years ago for primary immune deficiencies, marking the beginning of a vibrant field of translational and therapeutic research. Since then, many HSC-GT studies have been conducted in diverse genetic diseases. The approach has been improved over time, showing biological and therapeutic efficacy with an overall excellent safety record. Within a defined regulatory and ethical landscape, the field of HSC-GT has reached industrialization and commercialization stages, with a landmark recent approval by the European Medicines Agency of the first HSC-GT medicine for human use. At such a pivotal stage, it is important to look back at 25 years of European applied research in this field. This review highlights some of the key contributions of European teams to the field of HSC-GT, focusing in particular on the development of safer gene transfer vectors and international cooperation.
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