Molecular Farming of Plants and Animals for Human and Veterinary Medicine

by Erickson, Larry E.; Yu, W. J.; Brandle, J.; Rymerson, R.

• ISBN13: 9781402008351
• ISBN10: 140200835X
• Format: Hardcover
• Copyright: 2003-01-01
• Publisher: Kluwer Academic Pub

Summary

Until recently, agriculture was seen as a minor customer of the pharmaceutical industry. However, as this book amply demonstrates, agriculture may be poised to become a much more important supplier rather than consumer of pharmaceuticals. This book is the most comprehensive and up-to-date compilation of bio-farming strategies to provide health products that are both safer and lower-cost than those produced conventionally. The style and information presented assumes a university undergraduate level of genetics and biology. Technical information regarding the methods used and the results, as well as perspectives on commercialization and regulation, is provided by scientists prominent in this diverse and burgeoning field. This book is an invaluable resource for undergraduate and graduate students, university faculty, and researchers in government and corporate labs, as well as research managers, planners, and consultants in biotechnology.

Table of Contents

Preface	xvii
Tobacco, A Platform for the Production of Recombinant Proteins	1	(32)
R.T. Rymerson
R. Menassa
J.E. Brandle
Introduction	1	(1)
Agricultural Production of Biomass	2	(2)
Recombinant Protein Expression in Tobacco	4	(6)
Production in Seeds	4	(1)
Organelle Targeting	5	(1)
Chloroplast Transformation	6	(1)
Secretion to the Apoplast	7	(1)
Transient Expression	8	(2)
Examples	10	(14)
Antibodies	10	(2)
Biopharmaceuticals	12	(7)
Industrial Proteins	19	(2)
Vaccines	21	(3)
Conclusion	24	(9)
Alfalfa: An Efficient Bioreactor for Continuous Recombinant Protein Production	33	(16)
M.-A. D'Aoust
U. Busse
M. Martel
L. Faye
D. Levesque
L.P. Vezina
Introduction	33	(1)
Expression Cassettes	34	(2)
Transformation Methods	36	(4)
In vitro Culture	36	(1)
Transformation with Agrobacterium	37	(1)
Direct DNA Transfer	38	(1)
Other Methods	39	(1)
Population Ramp-Up	40	(1)
Extraction and Purification	41	(2)
Extraction and Purification	41	(2)
N-Glycosylation of Alfalfa Proteins	43	(1)
Case Study	43	(6)
Characteristics of an Anti-human IgG Produced in Alfalfa	43	(6)
The Use of Viral Vectors for the Production of Recombinant Proteins in Plants	49	(24)
G.P. Lomonossoff
Introduction	49	(1)
Choice of Virus for Vector Development	50	(1)
Types of Expression Systems	51	(1)
Examples of the Expression of Peptides and Proteins Using Viral Vectors	52	(14)
Tobacco Mosaic Virus	52	(5)
Cowpea Mosaic Virus	57	(3)
Tomato Bushy Stunt Virus	60	(2)
Plum Pox Virus	62	(1)
Other Potyviruses	63	(1)
Potato virus X	63	(2)
Tobacco Rattle Virus	65	(1)
Subviral Systems	65	(1)
Conclusions	66	(7)
Control of the N-Glycosylation of Therapeutic Glycoproteins Produced in Transgenic Plants: A New Challenge for Glycobiologists	73	(38)
P. Lerouge
M. Bardor
S. Pagny
V. Gomord
A.-C. Fitchette
L. Faye
Plant N-Linked Glycans and Their Differences with Their Mammalian Counterparts	74	(15)
Structures of Plant N-linked Glycans	74	(3)
Processing of N-linked Glycans in Plants	77	(5)
N-glycosylation and Folding of Proteins	82	(1)
Complex N-glycans Are Ubiquitous among the Plant Kingdom	83	(1)
Structural Analysis of Plant N-glycans	84	(5)
N-Glycosylation of Therapeutic Glycoproteins Produced in Transgenic Plants: Current Aspects and Future Trends	89	(11)
N-glycan Patterns of Therapeutic Glycoproteins Produced in Transgenic Plants	90	(1)
Immunogenicity and Allergenicity of Plant N-glycans	91	(1)
Metabolic Engineering of the Glycosylation in Plants to Obtain a Perfect Copy of Mammalian N-glycans	92	(8)
Future Perspectives	100	(11)
Production and Commercialization of Biopharmaceuticals from Milk	111	(16)
M.G.A. Peters
M.F. Brink
Introduction	111	(1)
The Rising Cost of Pharmaceuticals	112	(1)
Advances in Biotechnology	113	(2)
Livestock Versus Bacterial Fermentation	115	(1)
Transgenesis	116	(1)
Transgenic Milk Technology	117	(2)
Generating Transgenic Animals Through Micro-Injection	119	(1)
New Developments: Nuclear Transfer Technology	120	(2)
Pharming's Transgenic Cattle Platform	122	(1)
Effectiveness of the Transgenic Platform	122	(2)
Human Lactoferrin	123	(1)
Human Fibrinogen	123	(1)
Conclusion	124	(3)
A Seed-Derived Oral Subunit Vaccine for Human Cytomegalovirus	127	(28)
E.S. Tackaberry
K.E. Wright
A.K. Dudani
I. Altosaar
P.R. Ganz
Plants as Expression Systems for Biotherapeutics	128	(2)
Human Cytomegalovirus	130	(1)
Concerns and Challenges	131	(1)
Previous Work	132	(1)
Transfer of the HCMV Gb Gene to Tobacco	132	(3)
Vector Constructs and Transfer to Plants	132	(2)
Molecular Analysis of Plants Containing the HCMV gB Gene	134	(1)
Immunological Detection of gB and Quantification in Seed Protein Extracts	135	(2)
Extraction of Soluble Seed Proteins	135	(1)
gB-Specific ELISA	136	(1)
Antigenic Comparability of Seed-Derived gB vs. gB Produced in Infected Human Cells	137	(3)
Subcellular Localization of gB in Endosperm Tissue of Mature Transformed Seeds	140	(2)
General Discussion	142	(4)
Cloning, Transfer and Expression of gB Protein	143	(1)
Sub-cellular Localization of gB in Seed Endosperm	144	(1)
Sorting of gB in Endosperm Cells	145	(1)
Summary	146	(9)
Use of Plant Virus-Based Expression Systems for the Production of HIV Vaccines	155	(24)
G.G. Zhang
Introduction	156	(1)
Candidate Peptides and Proteins for HIV Vaccines	157	(3)
Expression of HIV Vaccines Using RNA Plant Virus-Based Expression Vectors	160	(11)
Presentation of the Kennedy Epitope from HIV-1 gp41 on the Surface of Cowpea Mosaic Virus	160	(4)
Expression of V3 Loop from Hiv-1 Gp120 Using Tobacco Mosaic Virus	164	(4)
Expression of an Epitope from V3 Loop of Hiv-1 Gp120 and the Full-length P24 Using Tomato Bushy Stunt Virus	168	(3)
Summary and Future Prospects	171	(8)
Suppression of Autoimmune Diabetes by the Use of Transgenic Plants Expressing Autoantigens to Induce Oral Tolerance	179	(18)
S. Ma
A.M. Jevnikar
Introduction	179	(2)
Oral Tolerance and the Treatment of Autoimmune Diseases	181	(2)
Unique Advantages of Using Transgenic Plants for Oral Tolerance Induction	183	(2)
Transgenic Plants Expressing Gad	185	(1)
Oral Immunogenicity of the Plant Derived Gad Protein	186	(3)
Expression of Cholera Toxin B Subunit (CTB)-Insulin Fusion Proteins	189	(1)
Expression of Human Gad65	190	(1)
Conclusions and Future Prospects	191	(6)
The Production and Delivery of Therapeutic Peptides in Plants	197	(26)
L. Erickson
W.-J. Yu
J. Zhang
C.F.M. deLange
B. McBride
S. Du
Plant Science in the Context of Veterinary and Medical Health	197	(1)
Significance of Intestinal Disease	198	(1)
Human	198	(1)
Animal	199	(1)
Intestinal Disease and the Role of the Epithelium	199	(1)
Growth Factors and the Epithelium	200	(2)
Epidermal Growth Factor	200	(1)
Glucagon-like Peptide-2	201	(1)
Antimicrobial Peptides and Intestinal Health	202	(1)
Plants Engineered to Contain Novel Therapeutic Peptides	203	(9)
Medicinal Plants	203	(1)
Expression of Xenoproteins in Plants: Problems and Strategies	204	(3)
Expression of Mammalian Proteins in Plants	207	(5)
Leaf-Based Production Systems: Advantages and Disadvantages	212	(2)
Delivery of Therapeutic Peptides to the Intestinal Tract	214	(1)
Regulatory Considerations	215	(8)
An Oral Vaccine in Maize Protects Against Transmissible Gastroenteritis Virus in Swine	223	(14)
J. Jilka
Introduction	223	(2)
Gene Constructs and Transformation of Maize Via Agrobacterium	225	(1)
Protocols for Feeding and Clinical Trials	226	(3)
Transgenic Grain Production	226	(1)
Swine Feeding Trials	226	(1)
Vaccination of Feed Test Groups	226	(1)
Virus Challenge	227	(1)
Data and Sample Collection	227	(1)
Data Analysis	228	(1)
Swine Feeding Trial #1 (TGEV-1)	229	(1)
Swine Feeding Trial #2 (TGEV-2)	229	(1)
Results from Clinical Trials	229	(3)
Observations of Clinical Symptoms for TGEV-1	229	(1)
Observations of Clinical Symptoms for TGEV-2	230	(2)
General Discussion	232	(5)
Production of Antibodies in Alfalfa (Medicago Sativa)	237	(22)
U. Busse
V. Levee
S. Trepanier
L. Vezina
Introduction	238	(3)
Antibodies in Human and Veterinary Medicine	238	(1)
Antibody Production: from Fermentors to Molecular Farming	239	(2)
Molecular Farming Using Alfalfa	241	(1)
Production Strategies in Alfalfa	242	(7)
Genetic Programming	242	(1)
Gene Transfer	243	(2)
Production of Biomass	245	(2)
Recovery of Recombinant Molecules	247	(1)
Disposal of Biomass	248	(1)
Case Study	249	(2)
Future Developments	251	(2)
Conclusion	253	(6)
The Production of Recombinant Antibodies in Plants and Plant Cells	259	(28)
R. Fischer
N. Emans
S. Schillberg
Introduction	259	(3)
Transgenic Plants as Bioreactors for Recombinant Protein Production	262	(5)
Antibody Engineering	263	(1)
Antibody Production in Transgenic Plants	263	(4)
Protein Expression in Plants	267	(4)
Agroinfiltration	268	(1)
Viral Vectors	268	(2)
Expression in Stably Transformed Plants	270	(1)
The Ideal Crop for Production of Recombinant Antibodies	270	(1)
Protein Production in Plant Suspension Cultured Cells	271	(3)
Suspension Cell Transformation	273	(1)
Downstream Processing of Recombinant Antibodies from Transgenic Plant Cells	274	(1)
Applications of Recombinant Antibodies Expressed in Plants	275	(2)
The Safety of Plant Produced Recombinant Antibodies	275	(1)
Using Recombinant Plant-Derived Antibodies in Human Health Care	276	(1)
Perspectives	277	(10)
Immunotherapeutic Potential of Antibodies Produced in Chicken Eggs	287	(32)
Y. Mine
J. Kovacs-Nolan
Introduction	288	(1)
Physiology of Chicken Egg Formation	289	(2)
Chicken Eggs as an Alternative Source of Antibodies	291	(6)
Structural Characteristics of Chicken Igy	293	(2)
Production and Isolation of Chicken IgY	295	(2)
Immunotherapeutic Potential of Chicken IgY	297	(12)
Application of IgY for the Prevention of Human Rotavirus Infection	297	(4)
Application of IgY for the Prevention of Yersinia ruckeri in Rainbow Trout	301	(1)
Application of IgY for the Prevention of Enterotoxigenic Escherichia coli Infection	302	(4)
Application of IgY for the Prevention of Salmonellosis	306	(2)
Other Applications of IgY	308	(1)
Conclusion and Future Studies	309	(10)
The Production of Recombinant Cytokines in Plants	319	(20)
R. Menassa
A. Jevnikar
J. Brandle
Introduction	319	(2)
Experimental Results from Plants	321	(10)
Human Erythropoietin	322	(1)
Human Interferons	323	(3)
Human Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF)	326	(1)
Human Interleukin-2	327	(1)
Human Interleukin-4	328	(3)
Production Platform Considerations	331	(1)
Quality Control and Standardization Issues	332	(1)
Conclusion	333	(6)
Edible Vaccines in Plants for Livestock Pathogens	339	(30)
L. Erickson
W.-J. Yu
T. Tuboly
E. Nagy
A. Bailey
J. Zhang
D. Yoo
S. Du
Introduction	339	(1)
Advantages of Edible Plant-Based Vaccines to Industry and the Consumer	340	(1)
Obstacles to the Development of Edible Plant-Based Vaccines	341	(5)
Expression Levels of Antigens in Plants	341	(2)
Degradation of Antigens in the Gut	343	(1)
Immunogenicity of Antigens Produced in Plants and Delivered Orally	344	(2)
Strategies for Production and Delivery of Edible Vaccines in Plants	346	(16)
Expression of Antigens Using Native Gene Constructs	346	(5)
Synthetic Genes	351	(4)
Fusion Proteins	355	(2)
Inducible Systems	357	(2)
Reducing Degradation and Enhancing Immunogenicity	359	(3)
Edible DNA Vaccines in Plants	362	(7)
Index	369