Feasibility of gene therapy in Gaucher disease using an adeno-associated virus vector.
Gaucher disease, one of the common lysosomal storage disorders, is caused by a deficiency of glucocerebrosidase (GC). We investigated gene transfer using recombinant adeno-associated viral (rAAV) vectors containing human GC cDNA driven by the human elongation factor 1-alpha promoter. This rAAV vector mediated efficient expression of human GC in human Gaucher fibroblasts. GC activities were increased from 2.8 to 3.4 times in normal fibroblast and from 1.9 to 4.6 times in Gaucher fibroblasts, and these increases in GC activity were maintained over 20 weeks. Intravenous administration of vectors via the hepatic portal vein and tail vein of wild-type mice resulted in efficient transduction into the tissues. GC activities of the liver, spleen, and lung in transduced mice were increased significantly up to two fold at 6 weeks after transduction. Significantly increased GC activities persisted over 20 weeks. Therefore, rAAV vector-mediated gene transfer may provide a therapeutic approach for the treatment of Gaucher disease.
Hong
Young Bin
YB
Division of Genetic Disease, Department of Biomedical Sciences, National Institute of Health, 5 Nokbun-Dong, Eunpyung-Gu, Seoul 122-701, South Korea.
Kim
Eun Young
EY
Division of Genetic Disease, Department of Biomedical Sciences, National Institute of Health, 5 Nokbun-Dong, Eunpyung-Gu, Seoul 122-701, South Korea.
Yoo
Han-Wook
HW
Department of Pediatrics, Medical Genetics Clinic and Laboratory, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
Jung
Sung-Chul
SC
Division of Genetic Disease, Department of Biomedical Sciences, National Institute of Health, 5 Nokbun-Dong, Eunpyung-Gu, Seoul 122-701, South Korea. jungsc@ewha.ac.kr.|Department of Biochemistry, College of Medicine, Ewha Womans University, Seoul, South Korea. jungsc@ewha.ac.kr.
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D000229:Dependovirus / Q000235:genetics*; D004705:Endocytosis; D005240:Feasibility Studies; D005776:Gaucher Disease / Q000628:therapy*; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL
D017931:DNA Primers