title: Immunomodulation of enzyme function in plants by single-domain antibody fragments.
abstract: Immunomodulation involves the use of antibodies to alter the function of molecules and is an emerging tool for manipulating both plant and animal systems. To realize the full potential of this technology, two major obstacles must be overcome. First, most antibodies do not function well intracellularly because critical disulfide bonds cannot form in the reducing environment of the cytoplasm or because of difficulties in targeting to subcellular organelles. Second, few antibodies bind to the active sites of enzymes and thus they generally do not neutralize enzyme function. Here we show that the unique properties of single-domain antibodies from camelids (camels and llamas) can circumvent both these obstacles. We demonstrate that these antibodies can be correctly targeted to subcellular organelles and inhibit enzyme function in plants more efficiently than antisense approaches. The use of these single-domain antibody fragments may greatly facilitate the successful immunomodulation of metabolic pathways in many organisms.
authors.affiliation: Unilever R&D Colworth, Sharnbrook, Bedford MK44 1LQ, UK. Steve.Jobling@Joblinghome.Freeserve.co.uk
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Jobling
authors.forename: Carl
authors.initials: C
authors.lastname: Jarman
authors.forename: Min-Min
authors.initials: MM
authors.lastname: Teh
authors.forename: Niklas
authors.initials: N
authors.lastname: Holmberg
authors.forename: Caroline
authors.initials: C
authors.lastname: Blake
authors.forename: Martine E
authors.initials: ME
authors.lastname: Verhoeyen
mesh_terms: D015061:1,4-alpha-Glucan Branching Enzyme / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000276:Adjuvants, Immunologic / Q000235:genetics / Q000378:metabolism*; D000688:Amylose / Q000032:analysis / Q000096:biosynthesis; D000818:Animals; D002161:Camelids, New World / Q000276:immunology / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000276:immunology / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000276:immunology; D018506:Gene Expression Regulation, Plant / Q000276:immunology; D007128:Immunoglobulin Fragments / Q000235:genetics / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000276:immunology*; D035281:Plant Tubers / Q000201:enzymology / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D030821:Plants, Genetically Modified / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011198:Solanum tuberosum / Q000201:enzymology / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D013213:Starch / Q000096:biosynthesis* / Q000737:chemistry / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D004791:Enzyme Inhibitors; D007128:Immunoglobulin Fragments; D007143:Immunoglobulin Heavy Chains; D013213:Starch; D000688:Amylose; D015061:1,4-alpha-Glucan Branching Enzyme