Gene Therapy in Fanconi anemia: a matter of time, safety and gene transfer tool efficiency.

Gene Therapy in Fanconi anemia: a matter of time, safety and gene transfer tool efficiency. Curr Gene Ther. 2017 Jan 09; Authors: Els V, Rodríguez FJ, Cosset FL, Lévy C, Rio P Abstract Fanconi anemia (FA) is a rare genetic syndrome characterized by progressive marrow failure. Gene therapy by infusion of FA-corrected autologous hematopoietic stem cells (HSCs) may offer a potential cure since it is a monogenetic disease with mutations in the FANC genes, coding for DNA repair enzymes (See review[1]). However, the collection of hCD34 +-cells in FA patients implies particular challenges because of the reduced numbers of progenitor cells present in their bone marrow (BM)[2] or mobilized peripheral blood[3-5]. In addition, the FA genetic defect fragilizes the HSCs[6]. These particular features might explain why the first clinical trials using murine leukemia virus derived retroviral vectors conducted for FA failed to show engraftment of corrected cells. The gene therapy field is now moving towards the use of lentiviral vectors (LVs) evidenced by recent succesful clinical trials for treatment of patients suffering from adrenoleukodystrophy (ALD)[7], β-thalassemia[8], metachromatic leukodystrophy[9] and Wiskott-Aldrich syndrome[10]. LV trials for X-linked severe combined immunodificiency and Fanconi anemia (FA) defects were recently initiated[11, 12]. Fifteen years of preclinical studies using different FA mouse models and in vitro researc...
Source: Current Gene Therapy - Category: Genetics & Stem Cells Authors: Tags: Curr Gene Ther Source Type: research