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Although enzyme replacement therapy (\n                    <jats:styled-content style=\"fixed-case\">ERT<\/jats:styled-content>\n                    ) is effective in treating patients with Pompe disease, formation of antibodies against rh\n                    <jats:styled-content style=\"fixed-case\">GAA<\/jats:styled-content>\n                    complicates treatment. In this report, we investigated induction of tolerance by oral administration of\n                    <jats:styled-content style=\"fixed-case\">GAA<\/jats:styled-content>\n                    expressed in chloroplasts. Because full\u2010length\n                    <jats:styled-content style=\"fixed-case\">GAA<\/jats:styled-content>\n                    could not be expressed, N\u2010terminal 410\u2010amino acids of\n                    <jats:styled-content style=\"fixed-case\">GAA<\/jats:styled-content>\n                    (as determined by T\u2010cell epitope mapping) were fused with the transmucosal carrier\n                    <jats:styled-content style=\"fixed-case\">CTB<\/jats:styled-content>\n                    . Tobacco transplastomic lines expressing\n                    <jats:styled-content style=\"fixed-case\">CTB<\/jats:styled-content>\n                    \u2010\n                    <jats:styled-content style=\"fixed-case\">GAA<\/jats:styled-content>\n                    were generated through site\u2010specific integration of transgenes into the chloroplast genome. Homoplasmic lines were confirmed by Southern blot analysis. Despite low\u2010level expression of\n                    <jats:styled-content style=\"fixed-case\">CTB<\/jats:styled-content>\n                    \u2010\n                    <jats:styled-content style=\"fixed-case\">GAA<\/jats:styled-content>\n                    in chloroplasts, yellow or albino phenotype of transplastomic lines was observed due to binding of\n                    <jats:styled-content style=\"fixed-case\">GAA<\/jats:styled-content>\n                    to a chloroplast protein that has homology to mannose\u20106 phosphate receptor. Oral administration of the plant\u2010made\n                    <jats:styled-content style=\"fixed-case\">CTB<\/jats:styled-content>\n                    \u2010\n                    <jats:styled-content style=\"fixed-case\">GAA<\/jats:styled-content>\n                    fusion protein even at 330\u2010fold lower dose (1.5\u00a0\u03bcg) significantly suppressed immunoglobulin formation against\n                    <jats:styled-content style=\"fixed-case\">GAA<\/jats:styled-content>\n                    in Pompe mice injected with 500\u00a0\u03bcg rh\n                    <jats:styled-content style=\"fixed-case\">GAA<\/jats:styled-content>\n                    per dose, with several\u2010fold lower titre of\n                    <jats:styled-content style=\"fixed-case\">GAA<\/jats:styled-content>\n                    \u2010specific IgG1 and IgG2a. Lyophilization increased\n                    <jats:styled-content style=\"fixed-case\">CTB<\/jats:styled-content>\n                    \u2010\n                    <jats:styled-content style=\"fixed-case\">GAA<\/jats:styled-content>\n                    concentration by 30\u2010fold (up to 190\u00a0\u03bcg per g of freeze\u2010dried leaf material), facilitating long\u2010term storage at room temperature and higher dosage in future investigations. This study provides the first evidence that oral delivery of plant cells is effective in reducing antibody responses in\n                    <jats:styled-content style=\"fixed-case\">ERT<\/jats:styled-content>\n                    for lysosomal storage disorders facilitating further advances in clinical investigations using plant cell culture system or\n                    <jats:italic>in\u00a0vitro<\/jats:italic>\n                    propagation.\n                  <\/jats:p>","DOI":"10.1111\/pbi.12413","type":"journal-article","created":{"date-parts":[[2015,6,5]],"date-time":"2015-06-05T12:52:06Z","timestamp":1433508726000},"page":"1023-1032","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["Oral delivery of Acid Alpha Glucosidase epitopes expressed in plant chloroplasts suppresses antibody formation in treatment of Pompe mice"],"prefix":"10.1111","volume":"13","author":[{"given":"Jin","family":"Su","sequence":"first","affiliation":[{"name":"Department of Biochemistry School of Dental Medicine University of Pennsylvania Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Sherman","sequence":"additional","affiliation":[{"name":"Department of Pediatrics College of Medicine University of Florida Gainesville FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip A.","family":"Doerfler","sequence":"additional","affiliation":[{"name":"Department of Pediatrics College of Medicine University of Florida Gainesville FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry J.","family":"Byrne","sequence":"additional","affiliation":[{"name":"Department of Pediatrics College of Medicine University of Florida Gainesville FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland W.","family":"Herzog","sequence":"additional","affiliation":[{"name":"Department of Pediatrics College of Medicine University of Florida Gainesville FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry","family":"Daniell","sequence":"additional","affiliation":[{"name":"Department of Biochemistry School of Dental Medicine University of Pennsylvania Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,6,5]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1098-934"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.9.4610"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1467-7652.2010.00582.x"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2003.08.004"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddr174"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1104\/pp.105.069468"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt0602-581"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0702219104"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt0498-345"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2001.4921"},{"key":"e_1_2_8_12_1","first-page":"111","article-title":"Chloroplast genetic engineering to improve agronomic traits","volume":"286","author":"Daniell H.","year":"2004","journal-title":"Methods Mol. 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