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Molecular Farming of Plants and Animals for Human and Veterinary Medicine PDF

381 Pages·2002·12.74 MB·English
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Molecular Farming of Plants and Animals for Human and Veterinary Medicine Molecular Farming of Plants and Animals for Human and Veterinary Medicine Edited by L. Erickson University of Guelph, Department (~f Plant Agriculture, Geulph, Ontario, Canada W.-J. Yu Syngenta Biotechnology Inc., Research Triangle Park, North Carolina, U.S.A. J. Brandle Research Branch, Agriculture and Agri-Food Canada, London, Ontario, Canada and R. Rymerson Research Branch, Agriculture and Agri-Food Canada, London, Ontario, Canada SPRINGER·SCIENCE+BUSINESS MEDIA, B.V. A C.I.P. Catalogue record for this book is available from the Library of Congress. ISBN 978-90-481-6110-2 ISBN 978-94-017-2317-6 (eBook) DOI 10.1007/978-94-017-2317-6 Printed on acid-free paper All Rights Reserved © 2002 Springer Science+Business Media Dordrecht Originally published by Kluwer Academic Publishers in 2002 Softcover reprint of the hardcover 1s t edition 2002 No part of this work may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording or otherwise, without written permission from the Publisher, with the exception of any material supplied specifically for the purpose of being entered and executed on a computer system, for exclusive use by the purchaser of the work. Contents Preface XVll 1. TOBACCO, A PLATFORM FOR THE PRODUCTION OF RECOMBINANT PROTEINS 1 R. T. Rymerson, R. Menassa and J.E. Brandle 1. INTRODUCTION 1 2. AGRICULTURAL PRODUCTION OF BIOMASS 2 3. RECOMBINANT PROTEIN EXPRESSION IN TOBACCO 4 3.1 Production in Seeds 4 3.2 Organelle Targeting 5 3.3 Chloroplast Transformation 6 3.4 Secretion to the Apoplast 7 3.5 Transient Expression 8 4. EXAMPLES 10 4.1 Antibodies 10 4.2 Biopharmaceuticals 12 4.3 Industrial Proteins 19 4.4 Vaccines 21 5. CONCLUSION 24 2. ALFALFA: AN EFFICIENT BIOREACTOR FOR CONTINUOUS RECOMBINANT PROTEIN PRODUCTION 33 M.-A. D'Aoust, U. Busse, M. Martel, L. Faye, D. Levesque and L.P. Vezina 1. INTRODUCTION 33 2. EXPRESSION CASSETTES 34 3. TRANSFORMATION METHODS 36 3.1 In vitro Culture 36 3.2 Transformation with Agrobacterium 37 3.3 Direct DNA Transfer 38 3.4 Other Methods 39 4. POPULATION RAMP-UP 40 5. EXTRACTION AND PURIFICATION 41 v VI Contents 5.1 Extraction and Purification 41 6. N-GLYCOSYLATION OF ALFALFA PROTEINS 43 7. CASE STUDY 43 7.1 Characteristics of an Anti-human IgG Produced in Alfalfa 43 3. THE USE OF VIRAL VECTORS FOR THE PRODUCTION OF RECOMBINANT PROTEINS IN PLANTS 49 G.P. Lomonossoff 1. INTRODUCTION 49 2. CHOICE OF VIRUS FOR VECTOR DEVELOPMENT 50 3. TYPES OF EXPRESSION SYSTEMS 51 4. EXAMPLES OF THE EXPRESSION OF PEPTIDES AND PROTEINS USING VIRAL VECTORS 52 4.1 Tobacco Mosaic Virus 52 4.2 Cowpea Mosaic Virus 57 4.3 Tomato Bushy Stunt Virus 60 4.4 Plum Pox Virus 62 4.5 Other Potyviruses 63 4.6 Potato virus X 63 4.7 Tobacco Rattle Virus 65 4.8 Subviral Systems 65 5. CONCLUSIONS 66 4. CONTROL OF THE N-GL YCOSYLATION OF THERAPEUTIC GLY COPROTEINS PRODUCED IN TRANSGENIC PLANTS: A NEW CHALLENGE FOR GLY COBIOLOGISTS 73 P. Lerouge, M. Bardor, S. Pagny, V. Gomord, A.-C. Fitchette andL. Faye 1. PLANT N-LINKED GL YCANS AND THEIR DIFFERENCES WITH THEIR MAMMALIAN COUNTERPARTS 74 1.1 Structures of Plant N-linked Glycans 74 1.2 Processing of N-linked Glycans in Plants 77 1.3 N-glycosylation and Folding of Proteins 82 1.4 Complex N-glycans Are Ubiquitous among the Plant Kingdom 83 1.5 Structural Analysis of Plant N-glycans 84 2. N-GLYCOSYLATION OF THERAPEUTIC GLY COPROTEINS PRODUCED IN TRANSGENIC Contents Vll PLANTS: CURRENT ASPECTS AND FUTURE TRENDS 89 2.1 N-glycan Patterns of Therapeutic Glycoproteins Produced in Transgenic Plants 90 2.2 Immunogenicity and Allergenicity of Plant N- glycans 91 2.3 Metabolic Engineering of the Glycosylation in Plants to Obtain a Perfect Copy of Mammalian N-glycans 92 3. FUTURE PERSPECTNES 100 5. PRODUCTION AND COMMERCIALIZATION OF BIOPHARMACEUTICALS FROM MILK 111 M.G.A. Peters and M.F. Brink 1. INTRODUCTION 111 2. THE RISING COST OF PHARMACEUTICALS 112 3. ADVANCES IN BIOTECHNOLOGY 113 4. LIVESTOCK VERSUS BACTERIAL FERMENTATION 115 5. TRANS GENESIS 116 6. TRANSGENIC MILK TECHNOLOGY 117 7. GENERATING TRANSGENIC ANIMALS THROUGH MICRO- INJECTION 119 8. NEW DEVELOPMENTS: NUCLEAR TRANSFER TECHNOLOGY 120 9. PHARMING'S TRANSGENIC CATTLE PLATFORM 122 10. EFFECTNENESS OF THE TRANSGENIC PLATFORM 122 10.1 Human Lactoferrin 123 10.2 Human Fibrinogen 123 11. CONCLUSION 124 6. A SEED-DERNED ORAL SUBUNIT VACCINE FOR HUMAN CYTOMEGALOVIRUS 127 E.S. Tackaberry, K.E. Wright, A.K. Dudani, I. Altosaar and P.R. Ganz 1. PLANTS AS EXPRESSION SYSTEMS FOR BIOTHERAPEUTICS 128 2. HUMAN CYTOMEGALOVIRUS 130 3. CONCERNS AND CHALLENGES 131 4. PREVIOUS WORK 132 5. TRANSFER OF THE HCMV Gb GENE TO TOBACCO 132 5.1 Vector Constructs and Transfer to Plants 132 V111 Contents 5.2 Molecular Analysis of Plants Containing the HCMV gBGene 134 6. Immunological Detection of gB and Quantification in Seed Protein Extracts 135 6.1 Extraction of Soluble Seed Proteins 135 6.2 gB-Specific ELISA 136 7. Antigenic Comparability of Seed-Derived gB vs. gB Produced in Infected Human Cells 137 8. Subcellular Localization of gB in Endosperm Tissue of Mature Transformed Seeds 140 9. GENERAL DISCUSSION 142 9.1 Cloning, Transfer and Expression of gB Protein 143 9.2 Sub-cellular Localization of gB in Seed Endosperm 144 9.3 Sorting of gB in Endosperm Cells 145 10. SUMMARY 146 7. USE OF PLANT VIRUS-BASED EXPRESSION SYSTEMS FOR THE PRODUCTION OF HIV VACCINES 155 G.G.Zhang 1. INTRODUCTION 156 2. CANDIDATE PEPTIDES AND PROTEINS FOR HIV VACCINES 157 3. EXPRESSION OF HIV VACCINES USING RNA PLANT VIRUS- BASED EXPRESSION VECTORS 160 3.1 Presentation of the Kennedy Epitope from HIV-l gp41 on the Surface of Cowpea Mosaic Virus 160 3.2 Expression of V3 Loop from Hiv-l Gp120 Using Tobacco Mosaic Virus 164 3.3 Expression of an Epitope from V3 Loop of Hiv-l Gp120 and the Full-length P24 Using Tomato Bushy Stunt Virus 168 4. SUMMARY AND FUTURE PROSPECTS 171 8. SUPPRESSION OF AUTOIMMUNE DIABETES BY THE USE OF TRANSGENIC PLANTS EXPRESSING AUTOANTIGENS TO INDUCE ORAL TOLERANCE 179 S. Ma and A.M. Jevnikar 1. INTRODUCTION 179 2. ORAL TOLERANCE AND THE TREATMENT OF AUTOIMMUNE DISEASES 181 3. UNIQUE ADVANTAGES OF USING TRANSGENIC PLANTS FOR ORAL TOLERANCE INDUCTION 183 Contents ix 4. TRANSGENIC PLANTS EXPRESSING GAD 185 5. ORAL IMMUNOGENICITY OF THE PLANT DERIVED GAD PROTEIN 186 6. EXPRESSION OF CHOLERA TOXIN B SUBUNIT (CTB)-INSULIN FUSION PROTEINS 189 7. EXPRESSION OF HUMAN GAD65 190 8. CONCLUSIONS AND FUTURE PROSPECTS 191 9. THE PRODUCTION AND DELIVERY OF THERAPEUTIC PEPTIDES IN PLANTS 197 L. Erickson, W.-J. Yu, J. Zhang, C.F.M. deLange, B .McBride and S. Du 1. PLANT SCIENCE IN THE CONTEXT OF VETERINARY AND MEDICAL HEALTH 197 2. SIGNIFICANCE OF INTESTINAL DISEASE 198 2.1 Human 198 2.2 Animal 199 3. INTESTINAL DISEASE AND THE ROLE OF THE EPITHELIUM 199 4. GROWTH FACTORS AND THE EPITHELIUM 200 4.1 Epidermal Growth Factor 200 4.2 Glucagon-like Peptide-2 201 5. ANTIMICROBIAL PEPTIDES AND INTESTINAL HEALTH 202 6. PLANTS ENGINEERED TO CONTAIN NOVEL THERAPEUTIC PEPTIDES 203 6.1 Medicinal Plants 203 6.2 Expression of Xenoproteins in Plants: Problems and Strategies 204 6.3 Expression of Mammalian Proteins in Plants 207 7. LEAF-BASED PRODUCTION SYSTEMS: ADVANTAGES AND DISADVANTAGES 212 8. DELIVERY OF THERAPEUTIC PEPTIDES TO THE INTESTINAL TRACT 214 9. REGULATORY CONSIDERATIONS 215 10. AN ORAL VACCINE IN MAIZE PROTECTS AGAINST TRANSMISSmLE GASTROENTERITIS VIRUS IN SWINE 223 J.Jilka 1. INTRODUCTION 223 x Contents 2. GENE CONSTRUCTS AND TRANSFORMATION OF MAIZE VIA AGROBACTERIUM 225 3. PROTOCOLS FOR FEEDING AND CLINICAL TRIALS 226 3.1 Transgenic Grain Production 226 3.2 Swine Feeding Trials 226 3.3 Vaccination of Feed Test Groups 226 3.4 Virus Challenge 227 3.5 Data and Sample Collection 227 3.6 Data Analysis 228 3.7 Swine Feeding Trial #1 (TGEV-1) 229 3.8 Swine Feeding Trial #2 (TGEV -2) 229 4. RESULTS FROM CLINICAL TRIALS 229 4.1 Observations of Clinical Symptoms for TGEV- 1 229 4.2 Observations of Clinical Symptoms for TGEV- 2 230 5. GENERAL DISCUSSION 232 11. PRODUCTION OF ANTIBODIES IN ALFALFA (MEDICAGO SATIVA) 237 U. Busse, V. Levee, S. Trepanier and L. Vezina 1. INTRODUCTION 238 1.1 Antibodies in Human and Veterinary Medicine 238 1.2 Antibody Production: from Fermentors to Molecular Farming 239 2. MOLECULAR FARMING USING ALFALFA 241 3. PRODUCTION STRATEGIES IN ALFALFA 242 3.1 Genetic Programming 242 3.2 Gene Transfer 243 3.3 Production of Biomass 245 3.4 Recovery of Recombinant Molecules 247 3.5 Disposal of Biomass 248 4. CASE STUDY 249 5. FUTURE DEVELOPMENTS 251 6. CONCLUSION 253 12. THE PRODUCTION OF RECOMBINANT ANTIBODIES IN PLANTS AND PLANT CELLS 259 R. Fischer, N. Emans and S. Schillberg 1. INTRODUCTION 259 2. TRANSGENIC PLANTS AS BIOREACTORS FOR RECOMBINANT PROTEIN PRODUCTION 262 2.1 Antibody Engineering 263 Contents xi 2.2 Antibody Production in Transgenic Plants 263 3. PROTEIN EXPRESSION IN PLANTS 267 3.1 Agroinfiltration 268 3.2 Viral Vectors 268 3.3 Expression in Stably Transformed Plants 270 3.4 The Ideal Crop for Production of Recombinant Antibodies 270 4. PROTEIN PRODUCTION IN PLANT SUSPENSION CULTURED CELLS 271 4.1 Suspension Cell Transformation 273 5. DOWNSTREAM PROCESSING OF RECOMBINANT ANTmODIES FROM TRANSGENIC PLANT CELLS 274 6. APPLICATIONS OF RECOMBINANT ANTmODIES EXPRESSED IN PLANTS 275 6.1 The Safety of Plant Produced Recombinant Antibodies 275 6.2 USING RECOMBINANT PLANT-DERIVED ANTmODIES IN HUMAN HEALTH CARE 276 7. PERSPECTIVES 277 13. IMMUNOTHERAPEUTIC POTENTIAL OF ANTmODIES PRODUCED IN CHICKEN EGGS 287 Y. Mine and J. Kovacs-Nolan 1. INTRODUCTION 288 2. PHYSIOLOGY OF CHICKEN EGG FORMATION 289 3. CHICKEN EGGS AS AN ALTERNATIVE SOURCE OF ANTmODIES 291 3.1 STRUCTURAL CHARACTERISTICS OF CHICKENIGY 293 3.2 Production and Isolation of Chicken IgY 295 4. IMMUNOTHERAPEUTIC POTENTIAL OF CHICKEN IGY297 4.1 Application of IgY for the Prevention of Human Rotavirus Infection 297 4.2 Application of Ig Y for the Prevention of Yersinia ruckeri in Rainbow Trout 301 4.3 Application of Ig Y for the Prevention of Enterotoxigenic Escherichia coli Infection 302 4.4 Application of IgY for the Prevention of Salmonellosis 306 4.5 Other Applications of IgY 308 5. CONCLUSION AND FUTURE STUDIES 309

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Molecular farming has been hailed as the "third wave" of genetically-modified organisms produced through biotechnology for the bio-based economy of the future. Unlike products of the first wave, such as herbicide resistant crop plants, which were perceived to benefit only the farmers who used them a
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