title: Customizing the genome as therapy for the β-hemoglobinopathies.
abstract: Despite nearly complete understanding of the genetics of the β-hemoglobinopathies for several decades, definitive treatment options have lagged behind. Recent developments in technologies for facile manipulation of the genome (zinc finger nucleases, transcription activator-like effector nucleases, or clustered regularly interspaced short palindromic repeats-based nucleases) raise prospects for their clinical application. The use of genome-editing technologies in autologous CD34(+) hematopoietic stem and progenitor cells represents a promising therapeutic avenue for the β-globin disorders. Genetic correction strategies relying on the homology-directed repair pathway may repair genetic defects, whereas genetic disruption strategies relying on the nonhomologous end joining pathway may induce compensatory fetal hemoglobin expression. Harnessing the power of genome editing may usher in a second-generation form of gene therapy for the β-globin disorders.
authors.affiliation: Division of Hematology/Oncology, Boston Children's Hospital, Boston, MA;
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Canver
authors.affiliation: Division of Hematology/Oncology, Boston Children's Hospital, Boston, MA; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA; Department of Pediatrics, Harvard Medical School and Harvard Stem Cell Institute, Harvard University, Boston, MA; and Howard Hughes Medical Institute, Boston, MA.
authors.forename: Stuart H
authors.initials: SH
authors.lastname: Orkin
mesh_terms: D000818:Animals; D064592:Autografts; D000072669:Gene Editing / Q000379:methods*; D018380:Hematopoietic Stem Cell Transplantation; D006453:Hemoglobinopathies / Q000235:genetics* / Q000628:therapy*; D006801:Humans; D052416:Targeted Gene Repair / Q000379:methods*