Abstract
Definitive cure of an animal model of a human disease by gene transfer into hematopoietic stem cells has not yet been accomplished in the absence of spontaneous in vivo selection for transduced cells. Erythropoietic protoporphyria is a genetic disease in which ferrochelatase is defective. Protoporphyrin accumulates in erythrocytes, leaks into the plasma and results in severe skin photosensitivity. Using a mouse model of erythropoietic protoporphyria, we demonstrate here that ex vivo preselection of hematopoietic stem cells transduced with a polycistronic retrovirus expressing both human ferrochelatase and green fluorescent protein results in complete and long-term correction of skin photosensitivity in all transplanted mice.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Bone Marrow Transplantation*
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Erythrocytes / metabolism
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Ferrochelatase / biosynthesis
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Ferrochelatase / genetics*
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Gene Transfer Techniques
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Genetic Therapy*
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Green Fluorescent Proteins
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Hematopoietic Stem Cells
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Humans
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Luminescent Proteins / biosynthesis
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Luminescent Proteins / genetics
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Male
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Mice
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Mice, Inbred BALB C
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Photosensitivity Disorders / blood
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Photosensitivity Disorders / pathology
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Photosensitivity Disorders / therapy*
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Porphyria, Hepatoerythropoietic / blood
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Porphyria, Hepatoerythropoietic / genetics
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Porphyria, Hepatoerythropoietic / therapy*
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Protoporphyria, Erythropoietic
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Protoporphyrins / blood
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Skin / pathology
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Transplantation, Isogeneic
Substances
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Luminescent Proteins
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Protoporphyrins
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Green Fluorescent Proteins
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Ferrochelatase