title: Gene therapy for monogenic disorders of the bone marrow.
abstract: Ex-vivo gene transfer of autologous haematopoietic stem cells in patients with monogenic diseases of the bone marrow has emerged as a new therapeutic approach, mainly in patients lacking a suitable donor for transplant. The encouraging results of initial clinical trials of gene therapy for primary immunodeficiencies were tempered by the occurrence of genotoxicity in a number of patients. Over the last decade, safer viral vectors have been developed to overcome the risk of insertional mutagenesis and have led to impressive clinical outcomes with considerably improved safety. We review the efforts in specific immunodeficiencies including adenosine deaminase deficiency, X-linked severe combined immunodeficiency, chronic granulomatous disease and Wiskott Aldrich syndrome. Major recent progress has also been made in haemoglobinopathies, such as beta-thalassaemia, sickle cell disease and Fanconi anaemia, and also specific lysosomal storage diseases, which, although not strictly bone marrow specific conditions, have been effectively treated by bone marrow-based treatment. The success of these recent studies and the advent of new technologies, such as gene editing, suggest that gene therapy could become a more generally applied treatment modality for a number of haematopoietic disorders.
authors.affiliation: Infection, Immunity, Inflammation and Physiological Medicine, Molecular and Cellular Immunology Section, University College London - Institute of Child Health, London, UK.|Department of Paediatric Oncology, Haematology and Clinical Immunology, Medical Faculty, Centre of Child and Adolescent Health, Heinrich-Heine-University, Düsseldorf, Germany.
authors.forename: Sujal
authors.initials: S
authors.lastname: Ghosh
authors.affiliation: Infection, Immunity, Inflammation and Physiological Medicine, Molecular and Cellular Immunology Section, University College London - Institute of Child Health, London, UK.
authors.forename: Adrian J
authors.initials: AJ
authors.lastname: Thrasher
authors.affiliation: Infection, Immunity, Inflammation and Physiological Medicine, Molecular and Cellular Immunology Section, University College London - Institute of Child Health, London, UK.
authors.forename: H Bobby
authors.initials: HB
authors.lastname: Gaspar
keywords: gene therapy; haemoglobinopathies; metabolic disorders; primary immunodeficiency