title: Plant-derived recombinant human serum transferrin  demonstrates multiple functions.
abstract: Human serum transferrin (hTf) is the major iron-binding protein in human plasma, having a vital role in iron transport. Additionally, hTf has many other uses including antimicrobial functions and growth factor effects on mammalian cell proliferation and differentiation. The multitask nature of hTf makes it highly valuable for different therapeutic and commercial applications. However, the success of hTf in these applications is critically dependent on the availability of high-quality hTf in large amounts. In this study, we have developed plants as a novel platform for the production of recombinant (r)hTf. We show here that transgenic plants are an efficient system for rhTf production, with a maximum accumulation of 0.25% total soluble protein (TSP) (or up to 33.5 microg/g fresh leaf weight). Furthermore, plant-derived rhTf retains many of the biological activities synonymous with native hTf. In particular, rhTf reversibly binds iron in vitro, exhibits bacteriostatic activity, supports cell proliferation in serum-free medium and can be internalized into mammalian cells in vitro. The success of this study validates the future application of plant rhTf in a variety of fields. Of particular interest is the use of plant rhTf as a novel carrier for cell-specific or oral delivery of protein/peptide drugs for the treatment of human diseases such as diabetes.To demonstrate this hypothesis, we have additionally expressed an hTf fusion protein containing glucagon-like peptide 1 (GLP-1) or its derivative in plants. Here, we show that plant-derived hTf-GLP-1 fusion proteins retain the ability to be internalized by mammalian cells when added to culture medium in vitro.
authors.affiliation: Department of Biology, University of Western Ontario, London, Ontario, Canada.
authors.forename: Martin E
authors.initials: ME
authors.lastname: Brandsma
authors.forename: Hong
authors.initials: H
authors.lastname: Diao
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Wang
authors.forename: Susanne E
authors.initials: SE
authors.lastname: Kohalmi
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Jevnikar
authors.forename: Shengwu
authors.initials: S
authors.lastname: Ma
mesh_terms: D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D004269:DNA, Bacterial / Q000235:genetics; D004337:Drug Carriers; D004705:Endocytosis / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D005822:Genetic Vectors / Q000235:genetics; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D006031:Glycosylation / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D007501:Iron / Q000378:metabolism; D051379:Mice; D008826:Microbial Sensitivity Tests; D030821:Plants, Genetically Modified; D011485:Protein Binding / Q000187:drug effects; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000254:growth & development; D011994:Recombinant Proteins / Q000378:metabolism* / Q000494:pharmacology; D014026:Nicotiana / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D014168:Transferrin / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D004269:DNA, Bacterial; D004337:Drug Carriers; D011994:Recombinant Proteins; C036483:T-DNA; D014168:Transferrin; D052216:Glucagon-Like Peptide 1; D007501:Iron