| First Author | Robert-Richard E | Year | 2008 |
| Journal | Am J Hum Genet | Volume | 82 |
| Issue | 1 | Pages | 113-24 |
| PubMed ID | 18179890 | Mgi Jnum | J:259557 |
| Mgi Id | MGI:6142612 | Doi | 10.1016/j.ajhg.2007.09.007 |
| Citation | Robert-Richard E, et al. (2008) Effective gene therapy of mice with congenital erythropoietic porphyria is facilitated by a survival advantage of corrected erythroid cells. Am J Hum Genet 82(1):113-24 |
| abstractText | Achieving long-term expression of a therapeutic gene in a given hematopoietic lineage remains an important goal of gene therapy. Congenital erythropoietic porphyria (CEP) is a severe autosomal-recessive disorder characterized by a deficiency in uroporphyrinogen III synthase (UROS), the fourth enzyme of the heme biosynthetic pathway. We used a recently obtained murine model to check the feasibility of gene therapy in this disease. Lentivirus-mediated transfer of the human UROS cDNA into hematopoietic stem cells (HSCs) from Uros(mut248) mice resulted in a complete and long-term enzymatic, metabolic, and phenotypic correction of the disease, favored by a survival advantage of corrected red blood cells. These results demonstrate that the cure of this mouse model of CEP at a moderate transduction level supports the proof of concept of a gene therapy in this disease by transplantation of genetically modified hematopoietic stem cells. |
