title: Gene Therapy for β-Hemoglobinopathies.
abstract: β-Thalassemia and sickle cell disease (SCD) are the world's two most widely disseminated hereditary hemoglobinopathies. β-Thalassemia originated in the Mediterranean, Middle Eastern, and Asian regions, and SCD originated in central Africa. However, subsequent population migration means that these two diseases are now global and thus constitute a growing health problem in many countries. Despite remarkable improvements in medical care for patients with β-hemoglobinopathies, there is still only one definitive treatment option: allogeneic hematopoietic stem cell (HSC) transplantation. The development of gene therapy for β-hemoglobinopathies has been justified by (1) the limited availability of human leukocyte antigen (HLA)-identical donors, (2) the narrow window of application of HSC transplantation to the youngest patients, and (3) recent advances in HSC-based gene therapy. The huge ongoing efforts in translational medicine and the high number of related publications show that gene therapy has the potential to become the treatment of choice for patients who lack either an HLA genoidentical sibling or an alternative, medically acceptable donor. In this dynamic scientific context, we first summarize the main steps toward clinical translation of this therapeutic approach and then discuss novel lentiviral- and genome editing-based treatment strategies for β-hemoglobinopathies.
authors.affiliation: Biotherapy Department, Necker Children's Hospital, Assistance Publique-Hôpitaux de Paris, 75015 Paris, France; Biotherapy Clinical Investigation Center, Assistance Publique-Hôpitaux de Paris, INSERM, Groupe Hospitalier Universitaire Ouest, 75015 Paris, France; INSERM UMR 1163, Laboratory of Human Lymphohematopoiesis, 75015 Paris, France; Paris Descartes, Sorbonne Paris Cité University, Imagine Institute, 75015 Paris, France. Electronic address: m.cavazzana@aphp.fr.
authors.forename: Marina
authors.initials: M
authors.lastname: Cavazzana
authors.affiliation: Paris Descartes, Sorbonne Paris Cité University, Imagine Institute, 75015 Paris, France; INSERM UMR 1163, Laboratory of Chromatin and Gene Regulation, 75015 Paris, France.
authors.forename: Chiara
authors.initials: C
authors.lastname: Antoniani
authors.affiliation: Paris Descartes, Sorbonne Paris Cité University, Imagine Institute, 75015 Paris, France; INSERM UMR 1163, Laboratory of Chromatin and Gene Regulation, 75015 Paris, France. Electronic address: annarita.miccio@institutimagine.org.
authors.forename: Annarita
authors.initials: A
authors.lastname: Miccio
mesh_terms: D000755:Anemia, Sickle Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D017988:Gammaretrovirus / Q000235:genetics / Q000276:immunology; D000072669:Gene Editing / Q000379:methods*; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000737:chemistry / Q000276:immunology; D006680:HLA Antigens; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D016086:Lentivirus / Q000235:genetics / Q000276:immunology; D009154:Mutation; D014019:Tissue Donors; D014184:Transplantation, Homologous; D055544:beta-Globins / Q000235:genetics* / Q000378:metabolism; D017086:beta-Thalassemia / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*
chemical_list: D006680:HLA Antigens; D055544:beta-Globins
keywords: gene therapy; hematopoietic stem cell; hemoglobinopathies; sickle cell disease; thalassemias