{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T12:42:28Z","timestamp":1790772148967,"version":"4.1.0"},"reference-count":25,"publisher":"National Academy of Sciences","issue":"24","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2008,6,17]]},"abstract":"<jats:p>\n                    Glycosaminoglycan storage begins in prenatal life in patients with mucopolysaccharidosis (MPS). In fact, prenatal hydrops is a common manifestation of MPS VII because of \u03b2-glucuronidase (GUS) deficiency. One way to address prenatal storage might be to deliver the missing enzyme across the placenta into the fetal circulation. Maternal IgG is transported across the placenta by the neonatal Fc receptor (FcRn), which recognizes the Fc domain of IgG and mediates transcytosis from maternal to fetal circulation. We hypothesized that we could exploit this process to deliver corrective enzyme to the fetus. To test this hypothesis, the C-terminal fusion protein, GUS-Fc, was compared with native, untagged, recombinant GUS for clearance from the maternal circulation, delivery to the fetus, and reduction of lysosomal storage in offspring of MPS VII mice. We observed that GUS-Fc, infused into pregnant mothers on embryonic days 17 and 18, was transported across the placenta. Similarly infused untagged GUS was not delivered to the fetus. GUS-Fc plasma enzyme activity in newborn MPS VII mice was 1,000 times that seen after administration of untagged GUS and \u2248100 times that of untreated WT newborns. Reduced lysosomal storage in heart valves, liver, and spleen provided evidence that\n                    <jats:italic>in utero<\/jats:italic>\n                    enzyme replacement therapy with GUS-Fc targeted sites of storage in the MPS VII fetus. We hypothesize that this noninvasive approach could deliver the missing lysosomal enzyme to a fetus with any lysosomal storage disease. It might also provide a method for inducing immune tolerance to the missing enzyme or another foreign protein.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0803715105","type":"journal-article","created":{"date-parts":[[2008,6,10]],"date-time":"2008-06-10T20:54:27Z","timestamp":1213131267000},"page":"8375-8380","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":38,"title":["Infused Fc-tagged \u03b2-glucuronidase crosses the placenta and produces clearance of storage\n                    <i>in utero<\/i>\n                    in mucopolysaccharidosis VII mice"],"prefix":"10.1073","volume":"105","author":[{"given":"Jeffrey H.","family":"Grubb","sequence":"first","affiliation":[{"name":"*Edward A. Doisy Department of Biochemistry and Molecular Biology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carole","family":"Vogler","sequence":"additional","affiliation":[{"name":"Department of Pathology, Saint Louis University School of Medicine, 1100 South Grand Boulevard, St. Louis, MO 63104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Tan","sequence":"additional","affiliation":[{"name":"*Edward A. Doisy Department of Biochemistry and Molecular Biology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gul N.","family":"Shah","sequence":"additional","affiliation":[{"name":"*Edward A. Doisy Department of Biochemistry and Molecular Biology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy F.","family":"MacRae","sequence":"additional","affiliation":[{"name":"*Edward A. Doisy Department of Biochemistry and Molecular Biology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William S.","family":"Sly","sequence":"additional","affiliation":[{"name":"*Edward A. Doisy Department of Biochemistry and Molecular Biology and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2008,6,17]]},"reference":[{"key":"e_1_3_3_1_2","first-page":"3421","volume-title":"The Metabolic and Molecular Bases of Inherited Disease","author":"Neufeld EF","year":"2001","unstructured":"EF Neufeld, J Muenzer, The Mucopolysaccharidoses. The Metabolic and Molecular Bases of Inherited Disease, eds CR Scriver, AL Beaudet, WS Sly, D Valle (McGraw\u2013Hill, New York), pp. 3421\u20133451 (2001)."},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.med.57.110104.115650"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M107778200"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0607053103"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1515\/JPM.2003.083"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri2155"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0712147105"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0308728100"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2005.02.031"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1069540"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.170.7.3528"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.22.8932"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0403235101"},{"key":"e_1_3_3_14_2","doi-asserted-by":"crossref","first-page":"6246","DOI":"10.4049\/jimmunol.154.12.6246","article-title":"Requirement for a \u03b22-microglobulin-associated Fc receptor for acquisition of maternal IgG by fetal and neonatal mice","volume":"154","author":"Israel EJ","year":"1995","unstructured":"EJ Israel, VK Patel, SF Taylor, A Marshak-Rothstein, NE Simister, Requirement for a \u03b22-microglobulin-associated Fc receptor for acquisition of maternal IgG by fetal and neonatal mice. J Immunol 154, 6246\u20136251 (1995).","journal-title":"J Immunol"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0264-410X(03)00336-0"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(78)90102-2"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M201875200"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(91)90434-D"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.26.14212"},{"key":"e_1_3_3_20_2","first-page":"969","article-title":"\u03b2-Glucuronidase deficiency mucopolysaccharidosis: Methods for enzymatic diagnosis","volume":"82","author":"Glaser JH","year":"1973","unstructured":"JH Glaser, WS Sly, \u03b2-Glucuronidase deficiency mucopolysaccharidosis: Methods for enzymatic diagnosis. J Lab Clin Med 82, 969\u2013977 (1973).","journal-title":"J Lab Clin Med"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)52451-6"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)41574-8"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/227680a0"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.74.5.2026"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.42.5.485"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0803715105","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T15:39:16Z","timestamp":1684424356000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0803715105"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,6,17]]},"references-count":25,"journal-issue":{"issue":"24","published-print":{"date-parts":[[2008,6,17]]}},"alternative-id":["10.1073\/pnas.0803715105"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0803715105","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,6,17]]},"assertion":[{"value":"2008-03-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2008-06-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}