{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T05:44:18Z","timestamp":1792734258974,"version":"4.5.0"},"reference-count":25,"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":[[1999,3,2]]},"abstract":"<jats:p>\n                    For many inborn errors of metabolism, early treatment is critical to prevent long-term developmental sequelae. We have used a gene-therapy approach to demonstrate this concept in a murine model of mucopolysaccharidosis type VII (MPS VII). Newborn MPS VII mice received a single intravenous injection with 5.4 \u00d7 10\n                    <jats:sup>6<\/jats:sup>\n                    infectious units of recombinant adeno-associated virus encoding the human \u03b2-glucuronidase (GUSB) cDNA. Therapeutic levels of GUSB expression were achieved by 1 week of age in liver, heart, lung, spleen, kidney, brain, and retina. GUSB expression persisted in most organs for the 16-week duration of the study at levels sufficient to either reduce or prevent completely lysosomal storage. Of particular significance, neurons, microglia, and meninges of the central nervous system were virtually cleared of disease. In addition, neonatal treatment of MPS VII mice provided access to the central nervous system via an intravenous route, avoiding a more invasive procedure later in life. These data suggest that gene transfer mediated by adeno-associated virus can achieve therapeutically relevant levels of enzyme very early in life and that the rapid growth and differentiation of tissues does not limit long-term expression.\n                  <\/jats:p>","DOI":"10.1073\/pnas.96.5.2296","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:39:15Z","timestamp":1027679955000},"page":"2296-2300","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":169,"title":["Neonatal gene transfer leads to widespread correction of pathology in a murine model of lysosomal storage disease"],"prefix":"10.1073","volume":"96","author":[{"given":"Thomas M.","family":"Daly","sequence":"first","affiliation":[{"name":"Departments of Pathology, Internal Medicine, and Genetics, Washington University School of Medicine, St. Louis, MO 63110; Department of Pathology, Saint Louis University School of Medicine, St. Louis, MO 63104; and Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carole","family":"Vogler","sequence":"additional","affiliation":[{"name":"Departments of Pathology, Internal Medicine, and Genetics, Washington University School of Medicine, St. Louis, MO 63110; Department of Pathology, Saint Louis University School of Medicine, St. Louis, MO 63104; and Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beth","family":"Levy","sequence":"additional","affiliation":[{"name":"Departments of Pathology, Internal Medicine, and Genetics, Washington University School of Medicine, St. Louis, MO 63110; Department of Pathology, Saint Louis University School of Medicine, St. Louis, MO 63104; and Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark E.","family":"Haskins","sequence":"additional","affiliation":[{"name":"Departments of Pathology, Internal Medicine, and Genetics, Washington University School of Medicine, St. Louis, MO 63110; Department of Pathology, Saint Louis University School of Medicine, St. Louis, MO 63104; and Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark S.","family":"Sands","sequence":"additional","affiliation":[{"name":"Departments of Pathology, Internal Medicine, and Genetics, Washington University School of Medicine, St. Louis, MO 63110; Department of Pathology, Saint Louis University School of Medicine, St. Louis, MO 63104; and Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1999,3,2]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(73)80162-3"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bi.61.070192.001515"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117237"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V78.11.3081.3081"},{"key":"e_1_3_3_5_2","first-page":"676","volume":"68","author":"Sands M S","year":"1993","unstructured":"M S Sands, J E Barker, C Vogler, B Levy, B Gwynn, N Galvin, W S Sly, E Birkenmeier Lab Invest 68, 676\u2013686 (1993).","journal-title":"Lab Invest"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI1773"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.81.20.6466"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0397-306"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1094-148"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.24.14082"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0797-270"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.13.6916"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.4.1426"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(95)01488-8"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1089\/10430349950019219"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.71.2.1079-1088.1997"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1006\/abio.1993.1197"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.3.685"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00418a070"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/360749a0"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1089\/hum.1998.9.8-1181"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/0165-3806(87)90107-6"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.72.1.180-190.1998"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.72.2.1593-1599.1998"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1119(96)00576-8"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.96.5.2296","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T17:38:20Z","timestamp":1649871500000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.96.5.2296"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,3,2]]},"references-count":25,"journal-issue":{"issue":"5","published-print":{"date-parts":[[1999,3,2]]}},"alternative-id":["10.1073\/pnas.96.5.2296"],"URL":"https:\/\/doi.org\/10.1073\/pnas.96.5.2296","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1999,3,2]]},"assertion":[{"value":"1998-11-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"1998-12-24","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"1999-03-02","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}