Long-term cure of the photosensitivity of murine erythropoietic protoporphyria by preselective gene therapy.
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.
Pawliuk
R
R
Massachusetts Institute of Technology, Division of Health Sciences & Technology, Cambridge 02139, USA.
Bachelot
T
T
Wise
R J
RJ
Mathews-Roth
M M
MM
Leboulch
P
P
D000818:Animals; D016026:Bone Marrow Transplantation; D004912:Erythrocytes / Q000378:metabolism; D005294:Ferrochelatase / Q000096:biosynthesis / Q000235:genetics*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D049452:Green Fluorescent Proteins; D006412:Hematopoietic Stem Cells; D006801:Humans; D008164:Luminescent Proteins / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010787:Photosensitivity Disorders / Q000097:blood / Q000473:pathology / Q000628:therapy*; D017121:Porphyria, Hepatoerythropoietic / Q000097:blood / Q000235:genetics / Q000628:therapy*; D046351:Protoporphyria, Erythropoietic; D011524:Protoporphyrins / Q000097:blood; D012867:Skin / Q000473:pathology; D014185:Transplantation, Isogeneic
D008164:Luminescent Proteins; D011524:Protoporphyrins; D049452:Green Fluorescent Proteins; D005294:Ferrochelatase