Medical Biotechnology by Bernard R. Glick

Medical Biotechnology
 
Author:
Bernard R. Glick, Terry L. Delovitch & Cheryl L. Patten
Publisher: American Society for Microbiology.
ISBN No: 978-1-55581-889-0
Release at: 2014
Pages: 758
Edition:
First Edition
File Size: 14 MB
File Type: pdf
Language: English



Description of Medical Biotechnology


From the very beginning of the biotechnology revolution in the early 1970s, many scientists understood that this new technology would radically change the way that we think about health care. They understood early on, well before any products were commercialized, that medical science was about to undergo a major paradigm shift in which all of our previous assumptions and approaches would change dramatically. 40 years later, the early promise has delivered by biotechnology.

Hundreds of new therapeutic agents, diagnostic tests, and vaccines have been developed and are currently available in the marketplace. Moreover, we are presently just at the tip of a very large iceberg it is clear, with many more products in the pipeline.

Content of Medical Biotechnology



SECTION I The Biology behind the Technology 1

1 Fundamental Technologies 3
Molecular Cloning 3
Preparation of DNA for Cloning 3
Insertion of Target DNA into a Plasmid Vector 7
Transformation and Selection of Cloned
DNA in a Bacterial Host 12
Cloning Eukaryotic Genes 15
Recombinational Cloning 19
Genomic Libraries 21
Amplifi cation of DNA Using PCR 24
DNA Sequencing Technologies 28
Dideoxynucleotide Procedure 31
Pyrosequencing 33
Sequencing Using Reversible Chain Terminators 35
Sequencing by Ligation 36
Sequencing Whole Genomes 38
Shotgun Cloning Strategy 39
High-Throughput Next-Generation Sequencing Strategies 41
Genomics 42
Transcriptomics 46
Proteomics 51
Metabolomics 63
SUMMARY 67
REVIEW QUESTIONS 68
REFERENCES 69
2 Fundamental Concepts in Immunology 71
The Immune Response 71
Overview of Infection and Immunity 71
Functions of the Immune System 73
Innate Immunity 75
Adaptive Immunity 81
Cells of the Immune System: Cell-Mediated
Immunity 88
Bone Marrow Precursor Cells 88
Myeloid Cells Mediate Innate Immunity 90
Lymphocytes 92
Antigen-Presenting Cells 96
Eff ector Cells 97
Tissues of the Immune System 97
Peripheral Lymphoid Organs 97
Lymphocyte Recirculation and Migration into Tissues 101
Antigen Recognition by T Cells 103
Humoral Immunity 114
Structure of Immunoglobulins 116
Functions of Immunoglobulins 118
Types of Antibodies: Applications 119
Polyclonal Antibodies 119
Antisera 120
Monoclonal Antibodies 120
Recombinant Antibodies 120
Immunological Techniques 122
Enzyme-Linked Immunosorbent Assay 123
Enzyme-Linked Immunospot Assay 125
Flow Cytometry 126
Mass Cytometry 128
Two-Photon Intravital Cell Imaging 129
SUMMARY 131
REVIEW QUESTIONS 132
REFERENCES 133
3 The Genetic Basis of Disease 135
Chromosomal Disorders and Gene Mapping 135
Chromosomes and Chromosome Abnormalities 135
Human Genome Mapping 146
Genome-Wide Association Studies 159
Single-Gene Disorders 164
Mode of Inheritance 164
Thalassemia 166
Sickle-Cell Anemia 167
Hemophilia 168
Cystic Fibrosis 169
Tay–Sachs Disease 170
Fragile X Syndrome 171
Huntington Disease 173
Polygenic Disorders and Gene Clustering 174
GWAS Strategies To Map Genes for Polygenic Disease 176
Breast Cancer 178
Alzheimer Disease 182
Type 1 Diabetes 185
Cardiovascular Disease 191
Mitochondrial Disorders 193
Disorders 193
Genetics 194
Mitochondrial Homeostasis and Parkinson Disease 195
Prevalence 199
Diagnosis and Prognosis 200
Treatment 201
SUMMARY 201
REVIEW QUESTIONS 202
REFERENCES 203
4 Immune Pathogenesis 207
Models of Immune System Lesions 207
Immunological Tolerance 207
Failure of Immune Tolerance and Development
of Autoimmune Disease 218
Immune Surveillance against Tumors 224
Immune Evasion by Tumors 229
Infl ammation and Immune Hypersensitivity
Disorders 229
Types of Infl ammation and Associated Immune
Hypersensitivity Reactions 230
Immediate Hypersensitivity 230
Therapy for Immediate Hypersensitivity 234
Antibody- and Antigen–Antibody Complex-Induced Disease 236
T-Cell-Mediated Diseases 239
Immunodefi ciency Disorders and Defects
in Development of the Immune System 241
Primary Immunodefi ciencies 242
Secondary Immunodefi ciencies 245
AIDS 245
SUMMARY 252
REVIEW QUESTIONS 253
REFERENCES 254
5 Microbial Pathogenesis 257
Introduction 257
Bacterial Infections 258
Attachment to Host Cells 258
Invasion and Dissemination 261
Evasion of Host Defenses and Proliferation 266
Damage to Host Tissues 272
Identifi cation of Bacterial Virulence Factors 279
Evolution of Bacterial Pathogens 285
Treatment of Bacterial Infections 290
Viral Infections 293
Attachment and Entry 295
Viral Gene Expression and Replication 300
Virus Assembly and Release 311
General Patterns of Viral Infections of Humans 315
Targets for Treatment of Viral Infections 320
SUMMARY 323
REVIEW QUESTIONS 324
REFERENCES 325

SECTION II Production of Therapeutic Agents 327

6 Modulation of Gene Expression 329
Manipulating Gene Expression in Prokaryotes 330
Promoters 331
Translational Regulation 334
Codon Usage 335
Protein Stability 336
Fusion Proteins 338
Metabolic Load 341
Chromosomal Integration 343
Increasing Secretion 346
Overcoming Oxygen Limitation 349
Reducing Acetate 350
Protein Folding 352
Heterologous Protein Production in Eukaryotic
Cells 354
Eukaryotic Expression Systems 354
Saccharomyces cerevisiae Expression Systems 356
Other Yeast Expression Systems 360
Baculovirus–Insect Cell Expression Systems 362
Mammalian Cell Expression Systems 368
Directed Mutagenesis 374
Oligonucleotide-Directed Mutagenesis with M13 DNA 374
Oligonucleotide-Directed Mutagenesis with Plasmid DNA 377
PCR-Amplifi ed Oligonucleotide-Directed Mutagenesis 377
Error-Prone PCR 379
Random Mutagenesis 381
DNA Shuffl ing 383
Examples of Modifi ed Proteins 384
SUMMARY 386
REVIEW QUESTIONS 388
REFERENCES 389
7 Genetic Engineering of Plants 393
Plant Transformation with the Ti Plasmid of
A. tumefaciens 396
Physical Transfer of Genes to Plants 401
Chloroplast Engineering 403
Transient Gene Expression 405
Molecular Pharming 408
Therapeutic Agents 408
Antibodies 411
Edible Vaccines 412
SUMMARY 418
REVIEW QUESTIONS 418
REFERENCES 419

SECTION III Diagnosing and Treating

Human Disease 421
8 Molecular Diagnostics 423
Immunological Approaches To Detect Protein
Biomarkers of Disease 424
Enzyme-Linked Immunosorbent Assays 424
Measuring Disease-Associated Proteins by Sandwich ELISA 428
Diagnosing Autoimmune Diseases by an Indirect ELISA 429
Immunoassays for Infectious Disease 430
Protein Arrays To Detect Polygenic Diseases 432
Immunoassays for Protein Conformation-Specifi c Disorders 435
DNA-Based Approaches to Disease Diagnosis 437
Hybridization Probes 437
Allele-Specifi c Hybridization 439
Oligonucleotide Ligation Assay 439
Padlock Probes 441
Allele-Specifi c PCR 442
TaqMan PCR 445
Real-Time PCR To Detect Infectious Disease 447
Detection of Multiple Disease-Associated
Mutations Using Microarrays 450
Detection of Epigenetic Markers 451
Detection of SNPs by Mass Spectrometry 454
Detecting RNA Signatures of Disease 457
Detection of Disease-Associated Changes in Gene
Expression Using Microarrays 457
Detection of RNA Signatures of Antibiotic
Resistance in Human Pathogens 457
Detection of miRNA Signatures of Cancers 460
SUMMARY 461
REVIEW QUESTIONS 462
REFERENCES 463
9 Protein Therapeutics 465
Pharmaceuticals 466
Interferon 466
Human Growth Hormone 471
Tumor Necrosis Factor 473
Targeting Mitochondria 474
Extending Protein Half-Life 476
Engineered Bacteriophages 477
Recombinant Antibodies 479
Preventing Rejection of Transplanted Organs 479
Hybrid Human–Mouse Monoclonal Antibodies 480
Human Monoclonal Antibodies 482
Antibody Fragments 484
Combinatorial Libraries of Antibody Fragments 488
Anticancer Antibodies 491
Antianthrax Antibodies 493
Antiobesity Antibodies 495
Enhanced Antibody Half-Life 496
Enzymes 497
DNase I 498
Alginate Lyase 499
Phenylalanine Ammonia Lyase 502
α1-Antitrypsin 504
Glycosidases 505
Lactic Acid Bacteria 507
Interleukin-10 507
Leptin 510
An HIV Inhibitor 511
Insulin 512
SUMMARY 514
REVIEW QUESTIONS 515
REFERENCES 515
10 Nucleic Acid Therapeutic Agents and Human
Gene Therapy 519
Treating Genetic and Nongenetic Disorders 519
Targeting Specifi c mRNAs and DNAs 522
Antisense RNA 522
Aptamers 525
Ribozymes 528
DNAzymes 530
Interfering RNA 530
Zinc Finger Nucleases 534
Viral Delivery Systems 535
Gammaretrovirus 535
Lentivirus 542
Adeno-Associated Virus 545
Adenovirus 549
Herpes Simplex Virus 1 555
Nonviral Nucleic Acid Delivery Systems 561
Direct Injection 561
Lipids 561
Bacteria 563
Dendrimers 565
Antibodies 566
Aptamers 566
Transposons 567
Prodrug Activation Therapy 569
Gene Therapy 571
Severe Combined Immunodefi ciency 571
Cancer 572
Eye Disorders 576
Muscle Disorders 578
Neurological Disorders 580
SUMMARY 587
REVIEW QUESTIONS 587
REFERENCES 588
11 Vaccines 593
Vaccination: Overview 593
Advantages 593
Limitations 595
Current Vaccine Design 598
Subunit Vaccines 601
Herpes Simplex Virus 602
Cholera 604
Severe Acute Respiratory Syndrome 605
Staphylococcus aureus 607
Human Papillomavirus 609
Peptide Vaccines 612
Malaria 612
Cancer 616
Autoimmune Disease 618
Allergy 620
Dendritic Cell Vaccines 622
Human Immunodefi ciency Virus 622
Cancer 623
DNA Vaccines 625
Delivery and Immune Mechanisms of Action 625
Advantages and Disadvantages 626
Improved Effi cacy and Immunogenicity 627
Attenuated Vaccines 634
Cholera 634
Salmonella Species 637
Leishmania Species 639
Poliovirus 639
Infl uenza Virus 640
Dengue Virus 643
Vector Vaccines 645
Vaccines Directed against Viruses 645
Vaccines Directed against Bacteria 651
Bacteria as Antigen Delivery Systems 655
Adjuvants 660
Systems Biology and Evaluation of Vaccines 663
SUMMARY 666
REVIEW QUESTIONS 667
REFERENCES 668
12 Societal Issues 671
Safety and Ethical Issues 672
Regulation of New Drugs 672
Regulation of Genetic and Genomic Testing 676
Patenting Biotechnology 678
Patenting 678
Patenting in Diff erent Countries 680
Patenting DNA Sequences 681
Patenting Living Organisms 683
Patenting and Fundamental Research 684
Economic Issues 684
SUMMARY 687
REVIEW QUESTIONS 688
REFERENCES 689
Glossary 691
Index 715

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