{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T09:14:03Z","timestamp":1793783643642,"version":"4.6.1"},"reference-count":41,"publisher":"National Academy of Sciences","issue":"5","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2001,2,27]]},"abstract":"<jats:p>Fabry disease is a lysosomal storage disorder caused by a\n deficiency of the lysosomal enzyme \u03b1-galactosidase A (\u03b1-gal A).\n This enzyme deficiency leads to impaired catabolism of\n \u03b1-galactosyl-terminal lipids such as globotriaosylceramide (Gb3).\n Patients develop painful neuropathy and vascular occlusions that\n progressively lead to cardiovascular, cerebrovascular, and renal\n dysfunction and early death. Although enzyme replacement therapy and\n bone marrow transplantation have shown promise in the murine analog of\n Fabry disease, gene therapy holds a strong potential for treating this\n disease in humans. Delivery of the normal \u03b1-gal A gene (cDNA) into a\n depot organ such as liver may be sufficient to elicit corrective\n circulating levels of the deficient enzyme. To investigate this\n possibility, a recombinant adeno-associated viral vector encoding human\n \u03b1-gal A (rAAV-AGA) was constructed and injected into the hepatic\n portal vein of Fabry mice. Two weeks postinjection, \u03b1-gal A\n activity in the livers of rAAV-AGA-injected Fabry mice was 20\u201335% of\n that of the normal mice. The transduced animals continued to show\n higher \u03b1-gal A levels in liver and other tissues compared with the\n untouched Fabry controls as long as 6 months after treatment. In\n parallel to the elevated enzyme levels, we see significant reductions\n in Gb3 levels to near normal at 2 and 5 weeks posttreatment. The lower\n Gb3 levels continued in liver, spleen, and heart, up to 25 weeks with\n no significant immune response to the virus or \u03b1-gal A. Also, no\n signs of liver toxicity occurred after the rAAV-AGA administration.\n These findings suggest that an AAV-mediated gene transfer may be useful\n for the treatment of Fabry disease and possibly other metabolic\n disorders.<\/jats:p>","DOI":"10.1073\/pnas.051634498","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:45:09Z","timestamp":1027680309000},"page":"2676-2681","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":115,"title":["Adeno-associated viral vector-mediated gene transfer results in long-term enzymatic and functional correction in multiple organs of Fabry mice"],"prefix":"10.1073","volume":"98","author":[{"given":"Sung-Chul","family":"Jung","sequence":"first","affiliation":[{"name":"Developmental and Metabolic Neurology Branch,\r Electron Microscopy Facility, National Institute of\r Neurological Disorders and Stroke, Laboratory of Cellular\r and Molecular Immunology, National Institute of Allergy and Infectious\r Diseases, National Institutes of Health, Bethesda, MD 20892;\r Department of Molecular Medicine, University of Auckland\r School of Medicine, 85 Park Road, Auckland, New Zealand; and\r Department of Neurosurgery, Thomas Jefferson University,\r Philadelphia, PA 19107"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ina P.","family":"Han","sequence":"additional","affiliation":[{"name":"Developmental and Metabolic Neurology Branch,\r Electron Microscopy Facility, National Institute of\r Neurological Disorders and Stroke, Laboratory of Cellular\r and Molecular Immunology, National Institute of Allergy and Infectious\r Diseases, National Institutes of Health, Bethesda, MD 20892;\r Department of Molecular Medicine, University of Auckland\r School of Medicine, 85 Park Road, Auckland, New Zealand; and\r Department of Neurosurgery, Thomas Jefferson University,\r Philadelphia, PA 19107"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Advait","family":"Limaye","sequence":"additional","affiliation":[{"name":"Developmental and Metabolic Neurology Branch,\r Electron Microscopy Facility, National Institute of\r Neurological Disorders and Stroke, Laboratory of Cellular\r and Molecular Immunology, National Institute of Allergy and Infectious\r Diseases, National Institutes of Health, Bethesda, MD 20892;\r Department of Molecular Medicine, University of Auckland\r School of Medicine, 85 Park Road, Auckland, New Zealand; and\r Department of Neurosurgery, Thomas Jefferson University,\r Philadelphia, PA 19107"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruian","family":"Xu","sequence":"additional","affiliation":[{"name":"Developmental and Metabolic Neurology Branch,\r Electron Microscopy Facility, National Institute of\r Neurological Disorders and Stroke, Laboratory of Cellular\r and Molecular Immunology, National Institute of Allergy and Infectious\r Diseases, National Institutes of Health, Bethesda, MD 20892;\r Department of Molecular Medicine, University of Auckland\r School of Medicine, 85 Park Road, Auckland, New Zealand; and\r Department of Neurosurgery, Thomas Jefferson University,\r Philadelphia, PA 19107"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monique P.","family":"Gelderman","sequence":"additional","affiliation":[{"name":"Developmental and Metabolic Neurology Branch,\r Electron Microscopy Facility, National Institute of\r Neurological Disorders and Stroke, Laboratory of Cellular\r and Molecular Immunology, National Institute of Allergy and Infectious\r Diseases, National Institutes of Health, Bethesda, MD 20892;\r Department of Molecular Medicine, University of Auckland\r School of Medicine, 85 Park Road, Auckland, New Zealand; and\r Department of Neurosurgery, Thomas Jefferson University,\r Philadelphia, PA 19107"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Zerfas","sequence":"additional","affiliation":[{"name":"Developmental and Metabolic Neurology Branch,\r Electron Microscopy Facility, National Institute of\r Neurological Disorders and Stroke, Laboratory of Cellular\r and Molecular Immunology, National Institute of Allergy and Infectious\r Diseases, National Institutes of Health, Bethesda, MD 20892;\r Department of Molecular Medicine, University of Auckland\r School of Medicine, 85 Park Road, Auckland, New Zealand; and\r Department of Neurosurgery, Thomas Jefferson University,\r Philadelphia, PA 19107"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamala","family":"Tirumalai","sequence":"additional","affiliation":[{"name":"Developmental and Metabolic Neurology Branch,\r Electron Microscopy Facility, National Institute of\r Neurological Disorders and Stroke, Laboratory of Cellular\r and Molecular Immunology, National Institute of Allergy and Infectious\r Diseases, National Institutes of Health, Bethesda, MD 20892;\r Department of Molecular Medicine, University of Auckland\r School of Medicine, 85 Park Road, Auckland, New Zealand; and\r Department of Neurosurgery, Thomas Jefferson University,\r Philadelphia, PA 19107"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary J.","family":"Murray","sequence":"additional","affiliation":[{"name":"Developmental and Metabolic Neurology Branch,\r Electron Microscopy Facility, National Institute of\r Neurological Disorders and Stroke, Laboratory of Cellular\r and Molecular Immunology, National Institute of Allergy and Infectious\r Diseases, National Institutes of Health, Bethesda, MD 20892;\r Department of Molecular Medicine, University of Auckland\r School of Medicine, 85 Park Road, Auckland, New Zealand; and\r Department of Neurosurgery, Thomas Jefferson University,\r Philadelphia, PA 19107"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew J.","family":"During","sequence":"additional","affiliation":[{"name":"Developmental and Metabolic Neurology Branch,\r Electron Microscopy Facility, National Institute of\r Neurological Disorders and Stroke, Laboratory of Cellular\r and Molecular Immunology, National Institute of Allergy and Infectious\r Diseases, National Institutes of Health, Bethesda, MD 20892;\r Department of Molecular Medicine, University of Auckland\r School of Medicine, 85 Park Road, Auckland, New Zealand; and\r Department of Neurosurgery, Thomas Jefferson University,\r Philadelphia, PA 19107"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roscoe O.","family":"Brady","sequence":"additional","affiliation":[{"name":"Developmental and Metabolic Neurology Branch,\r Electron Microscopy Facility, National Institute of\r Neurological Disorders and Stroke, Laboratory of Cellular\r and Molecular Immunology, National Institute of Allergy and Infectious\r Diseases, National Institutes of Health, Bethesda, MD 20892;\r Department of Molecular Medicine, University of Auckland\r School of Medicine, 85 Park Road, Auckland, New Zealand; and\r Department of Neurosurgery, Thomas Jefferson University,\r Philadelphia, PA 19107"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pankaj","family":"Qasba","sequence":"additional","affiliation":[{"name":"Developmental and Metabolic Neurology Branch,\r Electron Microscopy Facility, National Institute of\r Neurological Disorders and Stroke, Laboratory of Cellular\r and Molecular Immunology, National Institute of Allergy and Infectious\r Diseases, National Institutes of Health, Bethesda, MD 20892;\r Department of Molecular Medicine, University of Auckland\r School of Medicine, 85 Park Road, Auckland, New Zealand; and\r Department of Neurosurgery, Thomas Jefferson University,\r Philadelphia, PA 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