Rice seed ER-derived protein body as an efficient delivery vehicle for oral tolerogenic peptides
Mucosal delivery of peptide/protein therapeutics via the oral route is a desirable strategy in human immunotherapy. A key step for enhancing the bioavailability of orally administered therapeutics is to protect them from enzymatic digestion in the gastrointestinal tract. Here, we generated transgeni...
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| Veröffentlicht in: | Peptides (New York, N.Y. : 1980) N.Y. : 1980), 2010-08, Vol.31 (8), p.1421-1425 |
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| container_title | Peptides (New York, N.Y. : 1980) |
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| creator | Takagi, Hidenori Hiroi, Takachika Hirose, Sakiko Yang, Lijun Takaiwa, Fumio |
| description | Mucosal delivery of peptide/protein therapeutics via the oral route is a desirable strategy in human immunotherapy. A key step for enhancing the bioavailability of orally administered therapeutics is to protect them from enzymatic digestion in the gastrointestinal tract. Here, we generated transgenic rice seeds accumulating allergen-derived T cell epitopes, a model tolerogen for the control of pollen allergy, in either ER-derived protein body-I (PB-I) or protein storage vacuole protein body-II (PB-II). Compared with PB-II-localized or chemically synthesized forms, PB-I-localized T cell epitopes showed higher resistance to enzymatic digestion in simulated gastric fluid. Moreover, the dose of T cell epitope required for suppression of allergen-specific IgE in mice was about 20-fold lower when fed in PB-I localized form than when unprotected. These findings demonstrate the potential of bioencapsulation in PB-I for broad applications as a viable strategy to achieve efficient mucosal delivery of oral peptide/protein therapeutics. |
| doi_str_mv | 10.1016/j.peptides.2010.04.032 |
| format | Article |
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A key step for enhancing the bioavailability of orally administered therapeutics is to protect them from enzymatic digestion in the gastrointestinal tract. Here, we generated transgenic rice seeds accumulating allergen-derived T cell epitopes, a model tolerogen for the control of pollen allergy, in either ER-derived protein body-I (PB-I) or protein storage vacuole protein body-II (PB-II). Compared with PB-II-localized or chemically synthesized forms, PB-I-localized T cell epitopes showed higher resistance to enzymatic digestion in simulated gastric fluid. Moreover, the dose of T cell epitope required for suppression of allergen-specific IgE in mice was about 20-fold lower when fed in PB-I localized form than when unprotected. 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A key step for enhancing the bioavailability of orally administered therapeutics is to protect them from enzymatic digestion in the gastrointestinal tract. Here, we generated transgenic rice seeds accumulating allergen-derived T cell epitopes, a model tolerogen for the control of pollen allergy, in either ER-derived protein body-I (PB-I) or protein storage vacuole protein body-II (PB-II). Compared with PB-II-localized or chemically synthesized forms, PB-I-localized T cell epitopes showed higher resistance to enzymatic digestion in simulated gastric fluid. Moreover, the dose of T cell epitope required for suppression of allergen-specific IgE in mice was about 20-fold lower when fed in PB-I localized form than when unprotected. These findings demonstrate the potential of bioencapsulation in PB-I for broad applications as a viable strategy to achieve efficient mucosal delivery of oral peptide/protein therapeutics.</description><subject>Administration, Oral</subject><subject>Allergy immunotherapy</subject><subject>Animals</subject><subject>Antigens, Plant - genetics</subject><subject>Antigens, Plant - immunology</subject><subject>Computational fluid dynamics</subject><subject>Cytoplasmic Vesicles - metabolism</subject><subject>Cytoplasmic Vesicles - ultrastructure</subject><subject>Digestion</subject><subject>Dose-Response Relationship, Immunologic</subject><subject>Drug Delivery Systems</subject><subject>Endoplasmic Reticulum - metabolism</subject><subject>Epitopes, T-Lymphocyte - biosynthesis</subject><subject>Epitopes, T-Lymphocyte - genetics</subject><subject>Epitopes, T-Lymphocyte - immunology</subject><subject>Gastric Juice - metabolism</subject><subject>Hypersensitivity - prevention & control</subject><subject>Immunoglobulin E - blood</subject><subject>Immunoglobulin E - immunology</subject><subject>Immunosuppression</subject><subject>Lead (metal)</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mucosal delivery vehicle</subject><subject>Oral therapeutics</subject><subject>Oryza - genetics</subject><subject>Oryza - metabolism</subject><subject>Oryza sativa</subject><subject>Peptides</subject><subject>Peptides - administration & dosage</subject><subject>Peptides - genetics</subject><subject>Peptides - immunology</subject><subject>Peptides - metabolism</subject><subject>Plant Proteins - administration & dosage</subject><subject>Plant Proteins - genetics</subject><subject>Plant Proteins - immunology</subject><subject>Plant Proteins - metabolism</subject><subject>Plants, Genetically Modified - metabolism</subject><subject>Pollen - immunology</subject><subject>Proteins</subject><subject>Recombinant Fusion Proteins - administration & dosage</subject><subject>Recombinant Fusion Proteins - genetics</subject><subject>Recombinant Fusion Proteins - immunology</subject><subject>Recombinant Fusion Proteins - metabolism</subject><subject>Rice</subject><subject>Rice protein body</subject><subject>Seeds</subject><subject>Seeds - metabolism</subject><subject>Seeds - ultrastructure</subject><subject>Strategy</subject><issn>0196-9781</issn><issn>1873-5169</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1vGyEQhlHUKHHc_oWIW3tZh6-F5dYqSpNIkSJZyZmwMLRY68WFtSX_-2I57rE5gZhnmFfzIHRNyYISKm9Wiw1spuihLBipj0QsCGdnaEY7xZuWSv0JzQjVstGqo5foqpQVIUQI3V2gS0ZEq6hWM_S2jA5wAfD4btl4yHFXr5ucJogj7pPfY1uwHTGEEF2EccIehgrlPd7B7-gGwCFlnLId8JQGyOkXjNHhU7zP6DzYocCX93OOXn_evdw-NE_P94-3P54aJzibakopLdeMAQhlSe-10K3sguugFc4TAR23PfNK6EBrzXvFJbVdCFarnmk-R1-P_9bsf7ZQJrOOxcEw2BHSthjVilZyKtTHJOdaC8FEJb_9l6RKMkpVq7qKyiPqciolQzCbHNc27w0l5mDMrMxpJeZgzBBhqrHaeP0-Y9uvwf9rOymqwPcjAHV7uwjZlIMHBz5mcJPxKX404y-pdKqh</recordid><startdate>20100801</startdate><enddate>20100801</enddate><creator>Takagi, Hidenori</creator><creator>Hiroi, Takachika</creator><creator>Hirose, Sakiko</creator><creator>Yang, Lijun</creator><creator>Takaiwa, Fumio</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7U5</scope><scope>8FD</scope><scope>L7M</scope><scope>7X8</scope><scope>F1W</scope><scope>H95</scope><scope>L.G</scope></search><sort><creationdate>20100801</creationdate><title>Rice seed ER-derived protein body as an efficient delivery vehicle for oral tolerogenic peptides</title><author>Takagi, Hidenori ; Hiroi, Takachika ; Hirose, Sakiko ; Yang, Lijun ; Takaiwa, Fumio</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c432t-9766a3922ee47a0bd949568fc8e54cd04e83ab2d749f1949dd7361a8ffa97b293</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Administration, Oral</topic><topic>Allergy immunotherapy</topic><topic>Animals</topic><topic>Antigens, Plant - genetics</topic><topic>Antigens, Plant - immunology</topic><topic>Computational fluid dynamics</topic><topic>Cytoplasmic Vesicles - metabolism</topic><topic>Cytoplasmic Vesicles - ultrastructure</topic><topic>Digestion</topic><topic>Dose-Response Relationship, Immunologic</topic><topic>Drug Delivery Systems</topic><topic>Endoplasmic Reticulum - metabolism</topic><topic>Epitopes, T-Lymphocyte - biosynthesis</topic><topic>Epitopes, T-Lymphocyte - genetics</topic><topic>Epitopes, T-Lymphocyte - immunology</topic><topic>Gastric Juice - metabolism</topic><topic>Hypersensitivity - prevention & control</topic><topic>Immunoglobulin E - blood</topic><topic>Immunoglobulin E - immunology</topic><topic>Immunosuppression</topic><topic>Lead (metal)</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mucosal delivery vehicle</topic><topic>Oral therapeutics</topic><topic>Oryza - genetics</topic><topic>Oryza - metabolism</topic><topic>Oryza sativa</topic><topic>Peptides</topic><topic>Peptides - administration & dosage</topic><topic>Peptides - genetics</topic><topic>Peptides - immunology</topic><topic>Peptides - metabolism</topic><topic>Plant Proteins - administration & dosage</topic><topic>Plant Proteins - genetics</topic><topic>Plant Proteins - immunology</topic><topic>Plant Proteins - metabolism</topic><topic>Plants, Genetically Modified - metabolism</topic><topic>Pollen - immunology</topic><topic>Proteins</topic><topic>Recombinant Fusion Proteins - administration & dosage</topic><topic>Recombinant Fusion Proteins - genetics</topic><topic>Recombinant Fusion Proteins - immunology</topic><topic>Recombinant Fusion Proteins - metabolism</topic><topic>Rice</topic><topic>Rice protein body</topic><topic>Seeds</topic><topic>Seeds - metabolism</topic><topic>Seeds - ultrastructure</topic><topic>Strategy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Takagi, Hidenori</creatorcontrib><creatorcontrib>Hiroi, Takachika</creatorcontrib><creatorcontrib>Hirose, Sakiko</creatorcontrib><creatorcontrib>Yang, Lijun</creatorcontrib><creatorcontrib>Takaiwa, Fumio</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>Technology Research Database</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>MEDLINE - Academic</collection><collection>ASFA: Aquatic Sciences and Fisheries Abstracts</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) 1: Biological Sciences & Living Resources</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) Professional</collection><jtitle>Peptides (New York, N.Y. : 1980)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Takagi, Hidenori</au><au>Hiroi, Takachika</au><au>Hirose, Sakiko</au><au>Yang, Lijun</au><au>Takaiwa, Fumio</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Rice seed ER-derived protein body as an efficient delivery vehicle for oral tolerogenic peptides</atitle><jtitle>Peptides (New York, N.Y. : 1980)</jtitle><addtitle>Peptides</addtitle><date>2010-08-01</date><risdate>2010</risdate><volume>31</volume><issue>8</issue><spage>1421</spage><epage>1425</epage><pages>1421-1425</pages><issn>0196-9781</issn><eissn>1873-5169</eissn><abstract>Mucosal delivery of peptide/protein therapeutics via the oral route is a desirable strategy in human immunotherapy. A key step for enhancing the bioavailability of orally administered therapeutics is to protect them from enzymatic digestion in the gastrointestinal tract. Here, we generated transgenic rice seeds accumulating allergen-derived T cell epitopes, a model tolerogen for the control of pollen allergy, in either ER-derived protein body-I (PB-I) or protein storage vacuole protein body-II (PB-II). Compared with PB-II-localized or chemically synthesized forms, PB-I-localized T cell epitopes showed higher resistance to enzymatic digestion in simulated gastric fluid. Moreover, the dose of T cell epitope required for suppression of allergen-specific IgE in mice was about 20-fold lower when fed in PB-I localized form than when unprotected. These findings demonstrate the potential of bioencapsulation in PB-I for broad applications as a viable strategy to achieve efficient mucosal delivery of oral peptide/protein therapeutics.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>20457197</pmid><doi>10.1016/j.peptides.2010.04.032</doi><tpages>5</tpages></addata></record> |
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| identifier | ISSN: 0196-9781 |
| ispartof | Peptides (New York, N.Y. : 1980), 2010-08, Vol.31 (8), p.1421-1425 |
| issn | 0196-9781 1873-5169 |
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| subjects | Administration, Oral Allergy immunotherapy Animals Antigens, Plant - genetics Antigens, Plant - immunology Computational fluid dynamics Cytoplasmic Vesicles - metabolism Cytoplasmic Vesicles - ultrastructure Digestion Dose-Response Relationship, Immunologic Drug Delivery Systems Endoplasmic Reticulum - metabolism Epitopes, T-Lymphocyte - biosynthesis Epitopes, T-Lymphocyte - genetics Epitopes, T-Lymphocyte - immunology Gastric Juice - metabolism Hypersensitivity - prevention & control Immunoglobulin E - blood Immunoglobulin E - immunology Immunosuppression Lead (metal) Male Mice Mice, Inbred BALB C Mucosal delivery vehicle Oral therapeutics Oryza - genetics Oryza - metabolism Oryza sativa Peptides Peptides - administration & dosage Peptides - genetics Peptides - immunology Peptides - metabolism Plant Proteins - administration & dosage Plant Proteins - genetics Plant Proteins - immunology Plant Proteins - metabolism Plants, Genetically Modified - metabolism Pollen - immunology Proteins Recombinant Fusion Proteins - administration & dosage Recombinant Fusion Proteins - genetics Recombinant Fusion Proteins - immunology Recombinant Fusion Proteins - metabolism Rice Rice protein body Seeds Seeds - metabolism Seeds - ultrastructure Strategy |
| title | Rice seed ER-derived protein body as an efficient delivery vehicle for oral tolerogenic peptides |
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