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.