Update on gene therapy for hereditary hematological disorders

摘要: The past 3 years have been characterized by a number of impressive advances as well setbacks in gene therapy for genetic disease. Children with X-linked severe combined immunodeficiency disorder (SCID-X1) shown almost complete reconstitution their immune system after receiving retrovirally transduced autologous CD34+ hematopoietic stem cells (HSCs). However, two 11 treated patients subsequently developed leukemia-like disease probablydue to the undesired activation an oncogene. Gene transfer HSCs resulted substantial correction function and multi-lineage engraftment adenosine deaminase (ADA)-SCID. Several Phase I clinical trials treatment hemophilia A B initiated or completed. Partial A, albeit transient, has reported ex vivo fibroblasts. Intramuscular injection adeno-associated viral (AAV) vector evidence Factor IX skeletal muscle separate trial based on hepatic infusion AAV is ongoing. Sustained therapeutic levels coagulation factor expression achieved preclinical models using retroviral, lentiviral, high capacity adenoviral vectors. Efficient lentiviral HSC murine beta-thalassemia sickle cell demonstrated sustained phenotypic correction.