title: Gene Therapy of the β-Hemoglobinopathies by Lentiviral Transfer of the β(A(T87Q))-Globin Gene.
abstract: β-globin gene disorders are the most prevalent inherited diseases worldwide and result from abnormal β-globin synthesis or structure. Novel therapeutic approaches are being developed in an effort to move beyond palliative management. Gene therapy, by ex vivo lentiviral transfer of a therapeutic β-globin gene derivative (β(AT87Q)-globin) to hematopoietic stem cells, driven by cis-regulatory elements that confer high, erythroid-specific expression, has been evaluated in human clinical trials over the past 8 years. β(AT87Q)-globin is used both as a strong inhibitor of HbS polymerization and as a biomarker. While long-term studies are underway in multiple centers in Europe and in the United States, proof-of-principle of efficacy and safety has already been obtained in multiple patients with β-thalassemia and sickle cell disease.
authors.affiliation: 1 bluebird bio, Cambridge, Massachusetts.|2 CEA, Institute of Emerging Disease and Innovative Therapies (iMETI) , Fontenay aux Roses, France .
authors.forename: Olivier
authors.initials: O
authors.lastname: Negre
authors.affiliation: 1 bluebird bio, Cambridge, Massachusetts.
authors.forename: Anne-Virginie
authors.initials: AV
authors.lastname: Eggimann
authors.affiliation: 2 CEA, Institute of Emerging Disease and Innovative Therapies (iMETI) , Fontenay aux Roses, France .|3 UMR 007, University of Paris 11 and CEA , CEA-iMETI, Fontenay aux Roses, France .
authors.forename: Yves
authors.initials: Y
authors.lastname: Beuzard
authors.affiliation: 4 Necker Hospital , Assistance Publique-Hôpitaux de Paris, Paris, France .
authors.forename: Jean-Antoine
authors.initials: JA
authors.lastname: Ribeil
authors.affiliation: 4 Necker Hospital , Assistance Publique-Hôpitaux de Paris, Paris, France .
authors.forename: Philippe
authors.initials: P
authors.lastname: Bourget
authors.affiliation: 5 Mahidol University , Bangkok, Thailand .
authors.forename: Suparerk
authors.initials: S
authors.lastname: Borwornpinyo
authors.affiliation: 5 Mahidol University , Bangkok, Thailand .
authors.forename: Suradej
authors.initials: S
authors.lastname: Hongeng
authors.affiliation: 6 Immunology Laboratory, Groupe Hospitalier Universitaire Paris-Sud , Assistance Publique-Hôpitaux de Paris, Paris, France .
authors.forename: Salima
authors.initials: S
authors.lastname: Hacein-Bey
authors.affiliation: 4 Necker Hospital , Assistance Publique-Hôpitaux de Paris, Paris, France .
authors.forename: Marina
authors.initials: M
authors.lastname: Cavazzana
authors.affiliation: 2 CEA, Institute of Emerging Disease and Innovative Therapies (iMETI) , Fontenay aux Roses, France .|3 UMR 007, University of Paris 11 and CEA , CEA-iMETI, Fontenay aux Roses, France .|5 Mahidol University , Bangkok, Thailand .|7 Harvard Medical School and Genetics Division, Department of Medicine, Brigham & Women's Hospital , Boston, Massachusetts.
authors.forename: Philippe
authors.initials: P
authors.lastname: Leboulch
authors.affiliation: 2 CEA, Institute of Emerging Disease and Innovative Therapies (iMETI) , Fontenay aux Roses, France .|3 UMR 007, University of Paris 11 and CEA , CEA-iMETI, Fontenay aux Roses, France .|8 INSERM , Paris, France .
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Payen
mesh_terms: D000755:Anemia, Sickle Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D002986:Clinical Trials as Topic; D015870:Gene Expression; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000737:chemistry / Q000378:metabolism; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells; D006801:Humans; D016086:Lentivirus / Q000235:genetics / Q000378:metabolism; D061214:Patient Safety; D019076:Transgenes; D019172:Transplantation Conditioning / Q000379:methods; D055544:beta-Globins / Q000235:genetics* / Q000378:metabolism; D017086:beta-Thalassemia / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*
chemical_list: D055544:beta-Globins