Effective gene therapy of mice with congenital erythropoietic porphyria is facilitated by a survival advantage of corrected erythroid cells

Am J Hum Genet. 2008 Jan;82(1):113-24. doi: 10.1016/j.ajhg.2007.09.007.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Survival
  • Disease Models, Animal
  • Erythrocytes
  • Female
  • Genetic Therapy
  • Genetic Vectors
  • Hematopoietic Stem Cells
  • Lentivirus
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Porphyria, Erythropoietic / genetics*
  • Porphyria, Erythropoietic / therapy
  • Uroporphyrinogen III Synthetase / genetics*


  • Uroporphyrinogen III Synthetase