The Application of Clinical Genetics (Sep 2019)
Gene Therapy For Beta-Thalassemia: Updated Perspectives
Abstract
Garyfalia Karponi,1,* Nikolaos Zogas2,* 1Department of Veterinary Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece; 2Department of Biology, Aristotle University of Thessaloniki, Thessaloniki, Greece*These authors contributed equally to this workCorrespondence: Garyfalia KarponiLaboratory of Microbiology and Infectious Diseases, Faculty of Veterinary Medicine, Aristotle University of Thessaloniki, Thessaloniki 54124, GreeceTel +30 2310-999-956Fax +30 2310-999-934Email [email protected]: Allogeneic hematopoietic stem cell transplantation was until very recently, the only permanent curative option available for patients suffering from transfusion-dependent beta-thalassemia. Gene therapy, by autologous transplantation of genetically modified hematopoietic stem cells, currently represents a novel therapeutic promise, after many years of extensive preclinical research for the optimization of gene transfer protocols. Nowadays, clinical trials being held on a worldwide setting, have demonstrated that, by re-establishing effective hemoglobin production, patients may be rendered transfusion- and chelation-independent and evade the immunological complications that normally accompany allogeneic hematopoietic stem cell transplantation. The present review will offer a retrospective scope of the long way paved towards successful implementation of gene therapy for beta-thalassemia, and will pinpoint the latest strategies employed to increase globin expression that extend beyond the classic transgene addition perspective. A thorough search was performed using Pubmed in order to identify studies that provide a proof of principle on the aforementioned topic at a preclinical and clinical level. Inclusion criteria also regarded gene transfer technologies of the past two decades, as well as publications outlining the pitfalls that precluded earlier successful implementation of gene therapy for beta-thalassemia. Overall, after decades of research, that included both successes and pitfalls, the path towards a permanent, donor-irrespective cure for beta-thalassemia patients is steadily becoming a realistic approach.Keywords: gene therapy, gene editing, thalassemia, mobilization, viral vectors, clinical trials, hematopoietic stem cells
