Catalogo Articoli (Spogli Riviste)

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Titolo:
Gene therapy of a mouse model of protoporphyria with a self-inactivating erythroid-specific lentiviral vector without preselection
Autore:
Richard, E; Mendez, M; Mazurier, F; Morel, C; Costet, P; Xia, P; Fontanellas, A; Geronimi, F; Cario-Andre, M; Taine, L; Ged, C; Malik, P; de Verneuil, H; Moreau-Gaudry, F;
Indirizzi:
Univ V Segalen, Lab Pathol Mol & Therapie Gen EA 484, F-33076 Bordeaux, France Univ V Segalen Bordeaux France F-33076 EA 484, F-33076 Bordeaux, France Univ V Segalen, Serv Commun Anim Specialisee, F-33076 Bordeaux, France Univ V Segalen Bordeaux France F-33076 ialisee, F-33076 Bordeaux, France Childrens Hosp Los Angeles, Div Hematol Oncol, Los Angeles, CA 90027 USA Childrens Hosp Los Angeles Los Angeles CA USA 90027 Angeles, CA 90027 USA
Titolo Testata:
MOLECULAR THERAPY
fascicolo: 4, volume: 4, anno: 2001,
pagine: 331 - 338
SICI:
1525-0016(200110)4:4<331:GTOAMM>2.0.ZU;2-C
Fonte:
ISI
Lingua:
ENG
Soggetto:
CONGENITAL ERYTHROPOIETIC PORPHYRIA; BONE-MARROW TRANSPLANTATION; STABLE TRANSDUCTION; HOUSE MOUSE; STEM-CELLS; FERROCHELATASE; EXPRESSION; DISEASE; GLOBIN; PROMOTER;
Keywords:
ankyrin-1 promoter; erythroid specificity; ferrochelatase; gene transfer; gene therapy; hematopoietic stem cell; lentiviral vectors; porphyria; skin photosensitivity;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
37
Recensione:
Indirizzi per estratti:
Indirizzo: Moreau-Gaudry, F Univ V Segalen, Lab Pathol Mol & Therapie Gen EA 484, 146Rue Leo Saignat,F-33076 Bordeaux, France Univ V Segalen 146 Rue Leo Saignat Bordeaux France F-33076
Citazione:
E. Richard et al., "Gene therapy of a mouse model of protoporphyria with a self-inactivating erythroid-specific lentiviral vector without preselection", MOL THER, 4(4), 2001, pp. 331-338

Abstract

Successful treatment of blood disorders by gene therapy has several complications, one of which is the frequent lack of selective advantage of genetically corrected cells. Erythropoietic protoporphyria (EPP), caused by a ferrochelatase deficiency, is a good model of hematological genetic disorders with a lack of spontaneous in vivo selection. This disease is characterizedby accumulation of protoporphyrin in red blood cells, bone marrow, and other organs, resulting in severe skin photosensitivity. Here we develop a self-inactivating lentiviral vector containing human ferrochelatase cDNA driven by the human ankyrin-1/alpha -globin HS-40 chimeric erythroid promoter/enhancer. We collected bone marrow cells from EPP male donor mice for lentiviral transduction and injected them into lethally irradiated female EPP recipient mice. We observed a high transduction efficiency of hematopoietic stem cells resulting in effective gene therapy of primary and secondary recipient EPP mice without any selectable system. Skin photosensitivity was corrected for all secondary engrafted mice and was associated with specific ferrochelatase expression in the erythroid lineage. An erythroid-specific expression was sufficient to reverse most of the clinical and biological manifestations of the disease. This improvement in the efficiency of gene transferwith lentiviruses may contribute to the development of successful clinicalprotocols for erythropoietic diseases.

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Documento generato il 26/02/20 alle ore 06:09:14