Haema 2013; 4(3):301-308
by Georgios Vassilopoulos1, Eleni K. Siapati2
Gene Therapy Laboratory, Biomedical Research Foundation of the Academy of Athens, Athens, Greece
Abstract
Gene therapy of genetic hematological disorders entails the genetic modification of hematopoietic stem cells and the lifelong production of differentiated cells with normal phenotype. For delivery of the gene of interest, researchers have utilized retroviral vectors that possess the inherent capacity to insert their genome into the host DNA. At the clinical level, gene therapy has been successfully applied for the treatment of primary immunodeficiencies, b-thalassaemia, haemophilia and for the genetic modification of T lymphocytes. The existing vector technologies successfully achieve long-term gene expression but cannot guarantee targeted integration of the transgene in the host genome. This has led to severe adverse effects in gene therapy clinical trials, with patients developing leukemia due to vector insertional mutagenesis. At present, gene therapy is at the crossroads: it is futile to go on repeating mistakes of the past. Research ought to revisit certain issues and concentrate (i) on achieving gene correction in situ, (ii) on targeted vector integration in genetic safe harbors and (iii) on the development of episomal vectors. Until then, gene therapy can only be considered as a partially safe treatment option. Last but not least, cells are something more than simple medicine as they are permanently there, once transplanted.