title: Combining gene therapy and fetal hemoglobin induction for treatment of β-thalassemia.
abstract: β-thalassemias are caused by nearly 300 mutations of the β-globin gene, leading to a low or absent production of adult hemoglobin (HbA). Two major therapeutic approaches have recently been proposed: gene therapy and induction of fetal hemoglobin (HbF) with the objective of achieving clinically relevant levels of Hbs. The objective of this article is to describe the development of therapeutic strategies based on a combination of gene therapy and induction of HbFs. An increase of β-globin gene expression in β-thalassemia cells can be achieved by gene therapy, although de novo production of clinically relevant levels of adult Hb may be difficult to obtain. On the other hand, an increased production of HbF is beneficial in β-thalassemia. The combination of gene therapy and HbF induction appears to be a pertinent strategy to achieve clinically relevant results.
authors.affiliation: Department of Pediatrics, Division of Hematology-Oncology, Weill Cornell Medical College, New York, NY, USA. lab2002@med.cornell.edu
authors.forename: Laura
authors.initials: L
authors.lastname: Breda
authors.forename: Stefano
authors.initials: S
authors.lastname: Rivella
authors.forename: Cristina
authors.initials: C
authors.lastname: Zuccato
authors.forename: Roberto
authors.initials: R
authors.lastname: Gambari
mesh_terms: D000986:Antisickling Agents / Q000627:therapeutic use; D001374:Azacitidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000077209:Decitabine; D005319:Fetal Hemoglobin / Q000235:genetics / Q000378:metabolism*; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use; D016086:Lentivirus / Q000235:genetics; D012190:Retroviridae / Q000235:genetics; D013792:Thalidomide / Q000627:therapeutic use; D055544:beta-Globins / Q000235:genetics / Q000378:metabolism*; D017086:beta-Thalassemia / Q000628:therapy*
chemical_list: D000986:Antisickling Agents; D055544:beta-Globins; D013792:Thalidomide; D000077209:Decitabine; D005319:Fetal Hemoglobin; D001374:Azacitidine; D006918:Hydroxyurea