Gene therapy for hemoglobin disorders - a mini-review

Abstract

Gene therapy by either gene insertion or editing is an exciting curative therapeutic option for monogenic hemoglobin disorders like sickle cell disease and β-thalassemia. The safety and efficacy of gene transfer techniques has markedly improved with the use of lentivirus vectors. The clinical translation of this technology has met with good success, although key limitations include number of engraftable transduced hematopoietic stem cells and adequate transgene expression that results in complete correction of β0 thalassemia major. This highlights the need to identify and address factors that might be contributing to the in-vivo survival of the transduced hematopoietic stem cells or find means to improve expression from current vectors. In this review, we briefly discuss the gene therapy strategies specific to hemoglobinopathies, the success of the preclinical models and the current status of gene therapy clinical trials.

Lentiviral vector bioprocess economics for cell and gene therapy commercialization

“…ADA-SCID, WAS, MLD, X-ALD, X-SCID etc.) and haemoglobinopathies [30][31][32][33][34][35][36][37][38][39][40][41][42]. As in vivo gene therapy vectors, LVs are being clinically tested as a treatment for cystic fibrosis, macular degeneration and Parkinson's disease (Table 1).…”

Prenatal Gene Therapy for Metabolic Disorders

“…Treatment of other monogenic disorders and cancers has also been pursued. [8][9][10] In vivo gene therapy has been demonstrated extensively in animal models and has more recently been explored in human clinical trials. Although it holds significant promise, the clinical application of in vivo gene editing has been limited.…”

“…Monogenic hemoglobinopathies such as beta-thalassemia and sickle cell anemia are also among the candidates for potential ex vivo gene therapy including both replacement gene therapy and gene editing approaches. 9,34 Both disorders involve mutations in the beta-globin gene, either a quantitative problem in which too few globin subunits are produced (ie, thalassemia) or a qualitative problem in which an abnormal "sickled" form of hemoglobin is produced (ie, sickle cell anemia). In contrast to SCID, genetically corrected HSCs do not have a competitive advantage in sickle cell anemia and thalassemia.…”

“…Clinical application of ex vivo gene therapy and, more recently gene editing, has largely been used to treat hematologic and immunologic disorders by targeting hematopoietic stem cells (HSCs). Treatment of other monogenic disorders and cancers has also been pursued 8–10…”