title: Rice seed ER-derived protein body as an efficient delivery vehicle for oral tolerogenic peptides.
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.
authors.affiliation: Transgenic Crop Research and Development Center, National Institute of Agrobiological Sciences, 2-1-2 Kannondai, Tsukuba, Ibaraki 305-8602, Japan. hitakagi@affrc.go.jp
authors.forename: Hidenori
authors.initials: H
authors.lastname: Takagi
authors.forename: Takachika
authors.initials: T
authors.lastname: Hiroi
authors.forename: Sakiko
authors.initials: S
authors.lastname: Hirose
authors.forename: Lijun
authors.initials: L
authors.lastname: Yang
authors.forename: Fumio
authors.initials: F
authors.lastname: Takaiwa
mesh_terms: D000284:Administration, Oral; D000818:Animals; D052179:Antigens, Plant / Q000235:genetics / Q000276:immunology; D022162:Cytoplasmic Vesicles / Q000378:metabolism* / Q000648:ultrastructure; D004306:Dose-Response Relationship, Immunologic; D016503:Drug Delivery Systems; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D018984:Epitopes, T-Lymphocyte / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D005750:Gastric Juice / Q000378:metabolism; D006967:Hypersensitivity / Q000517:prevention & control*; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007165:Immunosuppression Therapy; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012275:Oryza / Q000235:genetics / Q000378:metabolism*; D010455:Peptides / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010940:Plant Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D030821:Plants, Genetically Modified / Q000378:metabolism; D011058:Pollen / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D012639:Seeds / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D052179:Antigens, Plant; C065290:Cry j I protein, Cryptomeria japonica; C065291:Cry j II protein, Cryptomeria japonica; D018984:Epitopes, T-Lymphocyte; D010455:Peptides; D010940:Plant Proteins; D011993:Recombinant Fusion Proteins; D007073:Immunoglobulin E