title: A phase I/II clinical trial of beta-globin gene therapy for beta-thalassemia.
abstract: Recent success in the long-term correction of mouse models of human beta-thalassemia and sickle cell anemia by lentiviral vectors and evidence of high gene transfer and expression in transduced human hematopoietic cells have led to a first clinical trial of gene therapy for the disease. A LentiGlobin vector containing a beta-globin gene (beta(A-T87Q)) that produces a hemoglobin (Hbbeta(A-T87Q)) that can be distinguished from normal hemoglobin will be used. The LentiGlobin vector is self-inactivating and contains large elements of the beta-globin locus control region as well as chromatin insulators and other features that should prevent untoward events. The study will be done in Paris with Eliane Gluckman as the principal investigator and Philippe Leboulch as scientific director.
authors.affiliation: Genetix Pharmaceuticals, Cambridge, Massachusetts 02139, USA. ab13@columbia.edu
authors.forename: Arthur
authors.initials: A
authors.lastname: Bank
authors.forename: Ronald
authors.initials: R
authors.lastname: Dorazio
authors.forename: Philippe
authors.initials: P
authors.lastname: Leboulch
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D002478:Cells, Cultured / Q000637:transplantation / Q000821:virology; D017321:Clinical Trials, Phase I as Topic / Q000379:methods*; D017322:Clinical Trials, Phase II as Topic / Q000379:methods*; D003062:Codon / Q000235:genetics; D003673:Defective Viruses / Q000235:genetics*; D005813:Genes, Synthetic; D015316:Genetic Therapy / Q000009:adverse effects; D005822:Genetic Vectors / Q000009:adverse effects / Q000235:genetics / Q000627:therapeutic use*; D005914:Globins / Q000737:chemistry / Q000235:genetics*; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000821:virology; D006801:Humans; D038101:Insulator Elements; D016086:Lentivirus / Q000235:genetics*; D007938:Leukemia / Q000209:etiology / Q000235:genetics / Q000517:prevention & control; D007942:Leukemia, Experimental / Q000209:etiology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008822:Mice, Transgenic; D016254:Mutagenesis, Insertional; D020125:Mutation, Missense; D010297:Paris; D018579:Patient Selection; D011323:Primates; D012107:Research Design; D020079:Terminal Repeat Sequences / Q000235:genetics; D014161:Transduction, Genetic; D055544:beta-Globins; D017086:beta-Thalassemia / Q000235:genetics / Q000628:therapy*
chemical_list: D003062:Codon; C443665:beta(A-T87Q) globin; D055544:beta-Globins; D005914:Globins