Delivery systems for genetic therapies of hematological disorders

Clinical cures for a number of monogenetic disorders of the blood and immune system have been accomplished in recent times. Depending on the tissues and cells affected by the inherited defect, different vector systems with specific gene delivery and expression profiles are needed for the genetic therapy to cure the clinical manifestations of the diseases. For all genetic disorders that can also be cured by the transplantation of allogeneic hematopoietic stem cells from healthy donors, integrating retroviral vectors are currently the gene transfer system of choice. Here, the transduction of the stem cells in vitro with HIV1-derived lentiviral vectors has set new standards for a number of pediatric disorders. Genetic therapies for 'hematological' monogenetic disorders such as hemophilia A or B have completely different target cells/organs and require different gene delivery systems that can be directly applied in vivo in patients. Here, AAV-based transgene delivery systems for specific targeting of liver cells will be compared to nonviral gene delivery platforms that might facilitate cheaper and possibly safer treatment options in the future.