title: A preclinical approach for gene therapy of beta-thalassemia.
abstract: Lentiviral-mediated beta-globin gene transfer successfully treated beta-thalassemic mice. Based on this result, clinical trials were initiated. To date, however, no study has investigated the efficacy of gene therapy in relation to the nature of the different beta-globin mutations found in patients. Most mutations can be classified as beta(0) or beta(+), based on the amount of beta-globin protein produced. Therefore, we propose that a screening in vitro is necessary to verify the efficacy of gene transfer prior to treatment of individual patients. We used a two-phase liquid culture system to expand and differentiate erythroid progenitor cells (ErPCs) transduced with lentiviral vectors. We propose the use of this system to test the efficiency of lentiviral vectors carrying the human beta-globin gene, to correct the phenotype of ErPCs from patients preparing for gene therapy. This new approach might have profound implications for designing gene therapy and for understanding the genotype/phenotype variability observed in Cooley's anemia patients.
authors: Department of Pediatrics, Division of Hematology-Oncology, Weill Cornell Medical College, Children's Blood and Cancer Foundation Laboratories, New York, New York, USA.
authors: Laura
authors: L
authors: Breda
authors: Dorothy A
authors: DA
authors: Kleinert
authors: Carla
authors: C
authors: Casu
authors: Laura
authors: L
authors: Casula
authors: Luca
authors: L
authors: Cartegni
authors: Eitan
authors: E
authors: Fibach
authors: Irene
authors: I
authors: Mancini
authors: Patricia J
authors: PJ
authors: Giardina
authors: Roberto
authors: R
authors: Gambari
authors: Stefano
authors: S
authors: Rivella
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics / Q000627:therapeutic use; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D051379:Mice; D009154:Mutation; D055544:beta-Globins / Q000235:genetics / Q000378:metabolism; D017086:beta-Thalassemia / Q000235:genetics* / Q000628:therapy*
chemical_list: D055544:beta-Globins