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Full Description
Discover the future of medicine in this extensively updated edition of the pioneering textbook, reflecting the rapid progress in the field
Molecular medicine is a rapidly growing field, and the molecular basis of diseases can be used to develop therapeutic approaches in numerous other medical subfields. Research into molecular medicine has been used as the basis for gene therapy, precision medicine, and more. Molecular Medicine provides a fundamental overview of this cutting-edge, interdisciplinary field, incorporating modules from basic immunology to virology to new approaches. Now fully updated to reflect the exponential progress in biomedical research, it promises to put students on the leading edge of a revolution in the life sciences.
Readers of the second edition of Molecular Medicine will also find:
Detailed discussion of cutting-edge topics including cancer stem cells, mRNA vaccines, organs-on-a-chip, and more
Professional artwork throughout
Chapter summaries, exercises, and study questions for each chapter
Molecular Medicine is ideal for graduate students in life sciences and medicine, as well as the lecturers and libraries that support them.
Contents
Preface xi
Acknowledgments xiii
About the Companion Website xv
1 Introduction 1
1.1 The Basics of Molecular Medicine 2
1.1.1 Topics of Molecular Medicine 2
1.1.2 Stages of Drug Development 3
1.2 The Human Cell 4
1.2.1 Organelles 5
1.2.1.1 The Nucleus 5
1.2.1.2 Mitochondria 6
1.2.1.3 Endoplasmic Reticulum and Golgi Apparatus 7
1.2.1.4 Peroxisome and Lysosome 8
1.2.2 Cell Cycle 8
1.2.3 Apoptosis 9
1.3 DNA Replication and Gene Expression 10
1.3.1 DNA Replication 11
1.3.2 Mutations 13
1.3.3 Transcription 14
1.3.4 Epigenetic Regulation of Gene Expression 19
1.3.5 Translation 22
1.3.6 Protein Degradation 25
1.4 Biological Communication 26
1.4.1 Neurotransmitters 26
1.4.2 Hormones 28
1.4.3 Signal Transduction 28
1.5 The Immune System 31
1.5.1 The Innate Immune System 32
1.5.1.1 The Complement System 33
1.5.2 The Adaptive Immune System 34
1.5.2.1 Cellular Immunity 34
1.5.2.2 Humoral Immunity 35
References 37
2 Methods in Molecular Medicine 41
2.1 DNA Microarrays 42
2.2 Quantitative Polymerase Chain Reaction 45
2.2.1 Basic Principles of Conventional PCR and Reverse-transcription PCR 46
2.2.2 Basic Principle of Real-time PCR 47
2.2.3 Reporter Dyes and Fluorescent Reporter Probes 48
2.3 Next-generation Sequencing 51
2.3.1 Second-generation Sequencing 52
2.3.2 Third-generation Sequencing 55
2.3.3 Exome Sequencing 56
2.3.4 RNA-Seq and Single-cell Sequencing 57
2.4 Proteomics 58
2.4.1 Two-dimensional Gel Electrophoresis and Mass Spectrometry 59
2.4.2 Quantitative and Shotgun Proteomics 62
2.4.3 Elucidation of Protein Structures 64
2.5 Animal Models in Biomedical Research 65
2.6 Alternatives to Animal Testing 68
2.6.1 3D Cell Culture, Spheroids, and Organoids 69
2.6.2 Bioprinting 70
2.6.3 Organ-on-a-Chip 72
2.6.4 Replacement of Animal Components in Biomedical Research 73
2.7 Additional Methods 74
2.7.1 Fluorescence Microscopy 74
2.7.2 Flow Cytometry and Fluorescence-activated Cell Sorting 76
2.7.3 Surface Plasmon Resonance 76
References 77
3 Genetic Disorders 81
3.1 Single-gene Disorders 82
3.1.1 Autosomal Dominant Disorders 85
3.1.1.1 Familial Hypercholesterolemia 85
3.1.1.2 Polycystic Kidney Disease 87
3.1.1.3 Marfan's Syndrome 88
3.1.1.4 Huntington's Disease 88
3.1.2 Autosomal Recessive Disorders 90
3.1.2.1 Cystic Fibrosis 90
3.1.2.2 Tay-Sachs Disease 92
3.1.2.3 Phenylketonuria 93
3.1.2.4 Xeroderma Pigmentosum 95
3.1.3 X-linked Recessive Disorders 96
3.1.3.1 Red-Green Color Blindness 96
3.1.3.2 Duchenne and Becker Muscular Dystrophy 97
3.1.4 Mitochondriopathies 98
3.2 Polygenic Disorders 101
3.2.1 Asthma 102
3.2.2 Diabetes Mellitus 103
References 105
4 Molecular Oncology 109
4.1 Basics of Oncology 110
4.1.1 Oncogenes and Tumor Suppressor Genes 110
4.1.2 Hallmarks of Cancer 111
4.1.3 Treatment Options for Cancer 111
4.2 Selected Cancer Diseases 112
4.2.1 Breast Cancer 112
4.2.2 Lung Cancer 114
4.2.3 Hepatocellular Carcinoma 116
4.2.4 Colorectal Cancer 117
4.2.5 Prostate Cancer 120
4.2.6 Hematological Malignancies 123
4.2.6.1 Leukemia 124
4.2.6.2 Further Hematological Malignancies 126
4.3 Oncolytic Virus Therapy 127
4.4 Cancer Stem Cells 128
4.5 Cancer Immunotherapy 130
4.5.1 CAR-T Cell Therapy 130
4.5.2 Immune Checkpoint Inhibitors 132
4.5.3 mRNA Cancer Vaccines 134
References 135
5 Molecular Virology 139
5.1 The Basics of Virology 140
5.1.1 Human Immunodeficiency Virus 143
5.1.2 Severe Acute Respiratory Syndrome Coronavirus 2 146
5.1.3 Hepatitis B Virus 147
5.1.4 Influenza Virus 148
5.2 Vaccination 149
5.2.1 Live Vaccines 151
5.2.1.1 Attenuated Virus Vaccines 151
5.2.1.2 Recombinant Virus Vaccines 154
5.2.2 Nonliving Vaccines 154
5.2.2.1 Inactivated Virus Vaccines 154
5.2.2.2 Subunit Vaccines 155
5.2.2.3 DNA Vaccines 156
5.2.2.4 mRNA Vaccines 156
5.2.3 HIV Vaccines 159
5.3 Detection of Viruses 159
5.3.1 Cytopathic Effects 159
5.3.2 Electron Microscopy 159
5.3.3 Hemagglutination Assay 160
5.3.4 Enzyme-linked Immunosorbent Assay 160
5.3.5 Indirect ELISA 160
5.3.6 Rapid Antigen Test 160
5.3.7 Polymerase Chain Reaction 161
5.3.8 Next-generation Sequencing 162
5.3.9 Antiviral Susceptibility Testing 163
5.4 Antiviral Therapy 163
5.4.1 Human Immunodeficiency Virus 167
5.4.2 Hepatitis C Virus 170
5.4.3 Influenza Virus 171
5.4.4 Other Viruses 172
5.5 Prions 172
References 173
6 Bacteria and Eukaryotic Pathogens 177
6.1 Bacteria 178
6.1.1 Virulence Factors 180
6.1.2 Serotypes 182
6.1.3 Examples of Bacterial Diseases 182
6.1.3.1 Tuberculosis 182
6.1.3.2 Pneumonia 183
6.1.3.3 Cholera 184
6.1.4 Biofilms 184
6.1.5 Bacterial Vaccines, Diagnostic Methods, and Antibiotics 184
6.1.5.1 Vaccines 184
6.1.5.2 Diagnostic Methods 185
6.1.5.3 Antibiotics 186
6.2 Eukaryotic Pathogens 192
6.2.1 Fungi 192
6.2.2 Protozoan Parasites 193
6.2.2.1 Plasmodium falciparum (Malaria) 193
6.2.3 Metazoan Parasites 195
References 196
7 Genomics 199
7.1 Whole Genome Sequencing 200
7.1.1 Cloning of DNA 200
7.1.2 Sequencing of Genomes 200
7.2 The Human Genome 202
7.2.1 Sequencing of the Human Genome 202
7.2.2 Interpretation of the Human Genome 204
7.2.3 Sequencing of Individual Human Genomes 208
7.3 Sequencing of Ancient DNA 209
7.3.1 The Neanderthal Genome Project 209
7.4 Follow-up Initiatives of the Human Genome Project 211
7.4.1 The International HapMap Project 211
7.4.2 The 1000 Genomes Project and the Personal Genome Project 212
7.4.3 Encyclopedia of DNA Elements (encode) 212
7.4.4 Further Genomic Projects 214
References 216
8 Genetic Testing 219
8.1 Types of Genetic Tests 220
8.1.1 Postnatal Genetic Tests 220
8.1.2 Prenatal Genetic Tests 222
8.2 Chromosome Abnormalities 224
8.2.1 Conventional Karyotyping 225
8.2.2 Fluorescence In Situ Hybridization 225
8.2.3 Comparative Genomic Hybridization 228
8.2.4 Optical Genome Mapping 229
8.3 Molecular Diagnosis 229
8.3.1 PCR-based Methods 229
8.3.2 DNA Microarray-based Methods 232
8.3.3 DNA Sequencing 234
References 236
9 Pharmacogenetics/Pharmacogenomics 239
9.1 Uptake and Transport of Drugs 242
9.2 Drug Metabolism 242
9.2.1 Cytochrome P450 Enzymes 243
9.2.2 Other Drug-metabolizing Enzymes 246
9.3 Drug Targeting 247
9.4 Drug Toxicity and Hypersensitivity 250
9.5 Drug Development and Individual Pharmacotherapy 250
References 252
10 Recombinant Protein Drugs 255
10.1 Production of Recombinant Proteins 258
10.1.1 Bacteria 259
10.1.2 Yeast and Other Fungi 260
10.1.3 Insect Cells 261
10.1.4 Mammalian Cells 261
10.1.5 Transgenic Animals and Plants 262
10.2 Classes of Recombinant Drugs 264
10.2.1 Monoclonal Antibodies 265
10.2.2 Hormones 272
10.2.3 Growth Factors 275
10.2.4 Fusion Proteins 277
10.2.5 Cytokines 278
10.2.6 Blood Coagulation Factors: Anticoagulants and Thrombolytics 279
10.2.7 Therapeutic Enzymes 281
10.2.8 Recombinant Vaccines 282
References 283
11 Gene Therapy 287
11.1 Types of Gene Therapy 288
11.2 Methods of Gene Transfer 289
11.2.1 Retroviral Vectors 290
11.2.2 Adenoviral Vectors 292
11.2.3 Adeno-associated Virus Vectors 293
11.2.4 Nonviral Gene Transfer 295
11.3 Tissue Specificity of Gene Transfer and Gene Expression 297
11.4 Applications of Gene Therapy 300
11.4.1 Gene Therapy of Monogenic Diseases 300
11.4.2 Gene Therapy of Cancer 303
11.4.3 Other Diseases 305
11.5 Genome Editing with CRISPR/Cas 305
11.6 Future Prospects 309
References 309
12 Stem Cells 313
12.1 Embryonic Stem Cells 315
12.1.1 Generation and Properties of Embryonic Stem Cells 315
12.1.2 Therapeutic Cloning 317
12.2 Adult Stem Cells 318
12.3 Induced Pluripotent Stem Cells 320
12.3.1 Generation of Induced Pluripotent Stem Cells 320
12.3.2 Properties of Induced Pluripotent Stem Cells 323
12.4 Transdifferentiation and Direct Reprogramming 323
12.5 Differentiation of Stem Cells 325
12.6 Medical Applications of Stem Cells 328
12.6.1 Adult Stem Cell Therapies 328
12.6.2 Pluripotent Stem Cells for Biomedical Research 330
12.6.3 Therapeutic Applications of Pluripotent Stem Cells 333
12.6.3.1 Applications in the Central Nervous System 334
12.6.3.2 Applications in the Eye 335
12.6.3.3 Diabetes 335
12.6.3.4 Heart Disease 336
12.6.3.5 Combinations of Stem Cell and Gene Therapy 337
References 338
13 Oligonucleotide-based Strategies 341
13.1 Antisense Oligonucleotides (ASOs) and Ribozymes 343
13.1.1 Mechanism of Action of ASOs 344
13.1.2 Development and Stabilization of ASO 345
13.1.3 Clinical Applications of ASO 347
13.1.4 Ribozymes 350
13.2 RNA Interference 351
13.2.1 Mechanism of RNAi 352
13.2.2 Nonspecific Side Effects 355
13.2.3 Stabilization and Delivery 356
13.2.4 Research and Preclinical Applications of RNAi 357
13.2.5 Clinical Applications of RNAi 358
13.3 MicroRNAs 361
13.3.1 The Biology of MicroRNAs 361
13.3.2 MicroRNAs and Disease 363
13.3.3 MicroRNA-Based Drugs in Clinical Development 366
13.4 Aptamers, Decoy Oligonucleotides, and Immunostimulatory Oligonucleotides 367
13.4.1 Aptamers 368
13.4.1.1 Selection of Aptamers 368
13.4.1.2 Modifications of Aptamers 371
13.4.1.3 Clinical Development of Aptamers 373
13.4.2 Decoy Oligonucleotides 375
13.4.3 Immunostimulatory Oligonucleotides 376
References 377
14 Ethics in Molecular Medicine 383
14.1 The Basis of Bioethics 384
14.2 Fields of Application 386
14.2.1 Genetic Testing and the "Right Not to Know" 386
14.2.2 Stem Cell Research 388
14.2.3 Preimplantation Genetic Diagnosis 390
14.2.4 Animal Experimentation 393
Abbreviations 399
Glossary 405
Index 409
