title: Effective gene therapy of mice with congenital erythropoietic porphyria is facilitated by a survival advantage of corrected erythroid cells.
abstract: 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.
authors.affiliation: Inserm U876, Institut Fédératif de Recherche 66, Bordeaux, F-33000 France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Robert-Richard
authors.forename: François
authors.initials: F
authors.lastname: Moreau-Gaudry
authors.forename: Magalie
authors.initials: M
authors.lastname: Lalanne
authors.forename: Isabelle
authors.initials: I
authors.lastname: Lamrissi-Garcia
authors.forename: Muriel
authors.initials: M
authors.lastname: Cario-André
authors.forename: Véronique
authors.initials: V
authors.lastname: Guyonnet-Dupérat
authors.forename: Laurence
authors.initials: L
authors.lastname: Taine
authors.forename: Cécile
authors.initials: C
authors.lastname: Ged
authors.forename: Hubert
authors.initials: H
authors.lastname: de Verneuil
mesh_terms: D000818:Animals; D002470:Cell Survival; D004195:Disease Models, Animal; D004912:Erythrocytes; D005260:Female; D015316:Genetic Therapy; D005822:Genetic Vectors; D006412:Hematopoietic Stem Cells; D016086:Lentivirus; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D017092:Porphyria, Erythropoietic / Q000235:genetics* / Q000628:therapy; D014576:Uroporphyrinogen III Synthetase / Q000235:genetics*
chemical_list: D014576:Uroporphyrinogen III Synthetase