Successful gene therapy of mice with congenital erythropoietic porphyria

被引：6

作者：

de Verneuil, Hubert ^{[1
]}

Robert-Richard, Elodie ^{[1
]}

Ged, Cecile ^{[1
]}

Mazurier, Frederic ^{[1
]}

Richard, Emmanuel ^{[1
]}

Moreau-Gaudry, Francois ^{[1
]}

机构：

[1] Univ Bordeaux 2, INSERM, U876, F-33076 Bordeaux, France

来源：

M S-MEDECINE SCIENCES | 2008年 / 24卷 / 6-7期

关键词：

D O I：

10.1051/medsci/20082467615

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Porphyrias are a group of disorders due to a genetic deficiency in one of the heme biosynthetic pathway enzymes. Congenital erythropoietic porphyria. (CEP) is the most severe type characterized by a deficiency in uroporphyrinogen III synthase (UROS) activity. Bone marrow transplantation represents a curative treatment for patients, as long as human leucocyte antigen-compatible donor is available. 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(mut 248) 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 for the first time that the cure of this mouse model of CEP at moderate transduction level supports the proof of concept of a gene therapy in this disease by transplantation of genetically modified HSCs.

引用

页码：615 / 619

页数：5

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