title: The therapeutic potential of genome editing for β-thalassemia.
abstract: The rapid advances in the field of genome editing using targeted endonucleases have called considerable attention to the potential of this technology for human gene therapy. Targeted correction of disease-causing mutations could ensure lifelong, tissue-specific expression of the relevant gene, thereby alleviating or resolving a specific disease phenotype. In this review, we aim to explore the potential of this technology for the therapy of β-thalassemia. This blood disorder is caused by mutations in the gene encoding the β-globin chain of hemoglobin, leading to severe anemia in affected patients. Curative allogeneic bone marrow transplantation is available only to a small subset of patients, leaving the majority of patients dependent on regular blood transfusions and iron chelation therapy. The transfer of gene-corrected autologous hematopoietic stem cells could provide a therapeutic alternative, as recent results from gene therapy trials using a lentiviral gene addition approach have demonstrated. Genome editing has the potential to further advance this approach as it eliminates the need for semi-randomly integrating viral vectors and their associated risk of insertional mutagenesis. In the following pages we will highlight the advantages and risks of genome editing compared to standard therapy for β-thalassemia and elaborate on lessons learned from recent gene therapy trials.
authors.affiliation: 1Murdoch Childrens Research Institute, Royal Children's Hospital, 50 Flemington Rd, Parkville, VIC, 3052, Australia; Department of Paediatrics, University of Melbourne, Royal Children's Hospital, 50 Flemington Rd, Parkville, VIC, 3052, Australia.
authors.forename: Astrid
authors.initials: A
authors.lastname: Glaser
authors.affiliation: 1Murdoch Childrens Research Institute, Royal Children's Hospital, 50 Flemington Rd, Parkville, VIC, 3052, Australia.
authors.forename: Bradley
authors.initials: B
authors.lastname: McColl
authors.affiliation: 1Murdoch Childrens Research Institute, Royal Children's Hospital, 50 Flemington Rd, Parkville, VIC, 3052, Australia; Department of Paediatrics, University of Melbourne, Royal Children's Hospital, 50 Flemington Rd, Parkville, VIC, 3052, Australia.
authors.forename: Jim
authors.initials: J
authors.lastname: Vadolas
keywords: gene therapy; genome; thalassemia