Cell and gene therapy for the beta-thalassemias: Advances and prospects Journal Article

Authors: Mansilla-Soto, J.; Riviere, I.; Boulad, F.; Sadelain, M.
Article Title: Cell and gene therapy for the beta-thalassemias: Advances and prospects
Abstract: The beta-thalassemias are inherited anemias caused by mutations that severely reduce or abolish expression of the beta-globin gene. Like sickle cell disease, a related beta-globin gene disorder, they are ideal candidates for performing a genetic correction in patient hematopoietic stem cells (HSCs). The most advanced approach utilizes complex lentiviral vectors encoding the human β-globin gene, as first reported by May et al. in 2000. Considerable progress toward the clinical implementation of this approach has been made in the past five years, based on effective CD34+ cell mobilization and improved lentiviral vector manufacturing. Four trials have been initiated in the United States and Europe. Of 16 evaluable subjects, 6 have achieved transfusion independence. One of them developed a durable clonal expansion, which regressed after several years without transformation. Although globin lentiviral vectors have so far proven to be safe, this occurrence suggests that powerful insulators with robust enhancer-blocking activity will further enhance this approach. The combined discovery of Bcl11a-mediated γ-globin gene silencing and advances in gene editing are the foundations for another gene therapy approach, which aims to reactivate fetal hemoglobin (HbF) production. Its clinical translation will hinge on the safety and efficiency of gene targeting in true HSCs and the induction of sufficient levels of HbF to achieve transfusion independence. Altogether, the progress achieved over the past 15 years bodes well for finding a genetic cure for severe globin disorders in the next decade. © 2016 Mary Ann Liebert, Inc.
Journal Title: Human Gene Therapy
Volume: 27
Issue: 4
ISSN: 1043-0342
Publisher: Mary Ann Liebert, Inc  
Date Published: 2016-04-13
Start Page: 295
End Page: 304
Language: English
DOI: 10.1089/hum.2016.037
PROVIDER: scopus
PUBMED: 27021486
PMCID: PMC4994056
Notes: Article -- Export Date: 2 June 2016 -- Source: Scopus
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MSK Authors
  1. Farid Boulad
    254 Boulad
  2. Michel W J Sadelain
    456 Sadelain
  3. Isabelle C Riviere
    164 Riviere