Molecular Medicine

Jens Kurreck, PhD, is a full Professor for Applied Biochemistry at the Technische Universität Berlin (TUB), Germany. He studied biochemistry and philosophy at the Free University of Berlin (FUB) and completed his PhD at the TUB in 1998. His research focuses on 3D bioprinting, RNA technologies, and virology. He has received several awards for his research achievements and teaching activities. Cy Aaron Stein, PhD, is Emeritus Professor of Oncology and Experimental Therapeutics and Chair of Medical Oncology at the City of Hope Medical Center in Duarte, CA, USA. He received a PhD in chemistry from Stanford University and an MD degree at the Albert Einstein College of Medicine, NY, in 1982. He has received numerous awards, among them the 2023 Life Achievement Award of the Oligonucleotide Therapeutics Society and a Clinical Career Development Award of the American Cancer Society.

Ein sehr gut strukturiertes, übersichtliches und sehr aktuelles Lehrbuch mit sehr gut erklärenden Abbildungen. (Dr. Ursula Hoja, Paracelsus Medizinische Universität, Nürnberg)

• Preface xiAcknowledgments xiiiAbout the Companion Website xv1 Introduction 11.1 The Basics of Molecular Medicine 21.1.1 Topics of Molecular Medicine 21.1.2 Stages of Drug Development 31.2 The Human Cell 41.2.1 Organelles 51.2.1.1 The Nucleus 51.2.1.2 Mitochondria 61.2.1.3 Endoplasmic Reticulum and Golgi Apparatus 71.2.1.4 Peroxisome and Lysosome 81.2.2 Cell Cycle 81.2.3 Apoptosis 91.3 DNA Replication and Gene Expression 101.3.1 DNA Replication 111.3.2 Mutations 131.3.3 Transcription 141.3.4 Epigenetic Regulation of Gene Expression 191.3.5 Translation 221.3.6 Protein Degradation 251.4 Biological Communication 261.4.1 Neurotransmitters 261.4.2 Hormones 281.4.3 Signal Transduction 281.5 The Immune System 311.5.1 The Innate Immune System 321.5.1.1 The Complement System 331.5.2 The Adaptive Immune System 341.5.2.1 Cellular Immunity 341.5.2.2 Humoral Immunity 35References 372 Methods in Molecular Medicine 412.1 DNA Microarrays 422.2 Quantitative Polymerase Chain Reaction 452.2.1 Basic Principles of Conventional PCR and Reverse-transcription PCR 462.2.2 Basic Principle of Real-time PCR 472.2.3 Reporter Dyes and Fluorescent Reporter Probes 482.3 Next-generation Sequencing 512.3.1 Second-generation Sequencing 522.3.2 Third-generation Sequencing 552.3.3 Exome Sequencing 562.3.4 RNA-Seq and Single-cell Sequencing 572.4 Proteomics 582.4.1 Two-dimensional Gel Electrophoresis and Mass Spectrometry 592.4.2 Quantitative and Shotgun Proteomics 622.4.3 Elucidation of Protein Structures 642.5 Animal Models in Biomedical Research 652.6 Alternatives to Animal Testing 682.6.1 3D Cell Culture, Spheroids, and Organoids 692.6.2 Bioprinting 702.6.3 Organ-on-a-Chip 722.6.4 Replacement of Animal Components in Biomedical Research 732.7 Additional Methods 742.7.1 Fluorescence Microscopy 742.7.2 Flow Cytometry and Fluorescence-activated Cell Sorting 762.7.3 Surface Plasmon Resonance 76References 773 Genetic Disorders 813.1 Single-gene Disorders 823.1.1 Autosomal Dominant Disorders 853.1.1.1 Familial Hypercholesterolemia 853.1.1.2 Polycystic Kidney Disease 873.1.1.3 Marfan’s Syndrome 883.1.1.4 Huntington’s Disease 883.1.2 Autosomal Recessive Disorders 903.1.2.1 Cystic Fibrosis 903.1.2.2 Tay–Sachs Disease 923.1.2.3 Phenylketonuria 933.1.2.4 Xeroderma Pigmentosum 953.1.3 X-linked Recessive Disorders 963.1.3.1 Red–Green Color Blindness 963.1.3.2 Duchenne and Becker Muscular Dystrophy 973.1.4 Mitochondriopathies 983.2 Polygenic Disorders 1013.2.1 Asthma 1023.2.2 Diabetes Mellitus 103References 1054 Molecular Oncology 1094.1 Basics of Oncology 1104.1.1 Oncogenes and Tumor Suppressor Genes 1104.1.2 Hallmarks of Cancer 1114.1.3 Treatment Options for Cancer 1114.2 Selected Cancer Diseases 1124.2.1 Breast Cancer 1124.2.2 Lung Cancer 1144.2.3 Hepatocellular Carcinoma 1164.2.4 Colorectal Cancer 1174.2.5 Prostate Cancer 1204.2.6 Hematological Malignancies 1234.2.6.1 Leukemia 1244.2.6.2 Further Hematological Malignancies 1264.3 Oncolytic Virus Therapy 1274.4 Cancer Stem Cells 1284.5 Cancer Immunotherapy 1304.5.1 CAR-T Cell Therapy 1304.5.2 Immune Checkpoint Inhibitors 1324.5.3 mRNA Cancer Vaccines 134References 1355 Molecular Virology 1395.1 The Basics of Virology 1405.1.1 Human Immunodeficiency Virus 1435.1.2 Severe Acute Respiratory Syndrome Coronavirus 2 1465.1.3 Hepatitis B Virus 1475.1.4 Influenza Virus 1485.2 Vaccination 1495.2.1 Live Vaccines 1515.2.1.1 Attenuated Virus Vaccines 1515.2.1.2 Recombinant Virus Vaccines 1545.2.2 Nonliving Vaccines 1545.2.2.1 Inactivated Virus Vaccines 1545.2.2.2 Subunit Vaccines 1555.2.2.3 DNA Vaccines 1565.2.2.4 mRNA Vaccines 1565.2.3 HIV Vaccines 1595.3 Detection of Viruses 1595.3.1 Cytopathic Effects 1595.3.2 Electron Microscopy 1595.3.3 Hemagglutination Assay 1605.3.4 Enzyme-linked Immunosorbent Assay 1605.3.5 Indirect ELISA 1605.3.6 Rapid Antigen Test 1605.3.7 Polymerase Chain Reaction 1615.3.8 Next-generation Sequencing 1625.3.9 Antiviral Susceptibility Testing 1635.4 Antiviral Therapy 1635.4.1 Human Immunodeficiency Virus 1675.4.2 Hepatitis C Virus 1705.4.3 Influenza Virus 1715.4.4 Other Viruses 1725.5 Prions 172References 1736 Bacteria and Eukaryotic Pathogens 1776.1 Bacteria 1786.1.1 Virulence Factors 1806.1.2 Serotypes 1826.1.3 Examples of Bacterial Diseases 1826.1.3.1 Tuberculosis 1826.1.3.2 Pneumonia 1836.1.3.3 Cholera 1846.1.4 Biofilms 1846.1.5 Bacterial Vaccines, Diagnostic Methods, and Antibiotics 1846.1.5.1 Vaccines 1846.1.5.2 Diagnostic Methods 1856.1.5.3 Antibiotics 1866.2 Eukaryotic Pathogens 1926.2.1 Fungi 1926.2.2 Protozoan Parasites 1936.2.2.1 Plasmodium falciparum (Malaria) 1936.2.3 Metazoan Parasites 195References 1967 Genomics 1997.1 Whole Genome Sequencing 2007.1.1 Cloning of DNA 2007.1.2 Sequencing of Genomes 2007.2 The Human Genome 2027.2.1 Sequencing of the Human Genome 2027.2.2 Interpretation of the Human Genome 2047.2.3 Sequencing of Individual Human Genomes 2087.3 Sequencing of Ancient DNA 2097.3.1 The Neanderthal Genome Project 2097.4 Follow-up Initiatives of the Human Genome Project 2117.4.1 The International HapMap Project 2117.4.2 The 1000 Genomes Project and the Personal Genome Project 2127.4.3 Encyclopedia of DNA Elements (encode) 2127.4.4 Further Genomic Projects 214References 2168 Genetic Testing 2198.1 Types of Genetic Tests 2208.1.1 Postnatal Genetic Tests 2208.1.2 Prenatal Genetic Tests 2228.2 Chromosome Abnormalities 2248.2.1 Conventional Karyotyping 2258.2.2 Fluorescence In Situ Hybridization 2258.2.3 Comparative Genomic Hybridization 2288.2.4 Optical Genome Mapping 2298.3 Molecular Diagnosis 2298.3.1 PCR-based Methods 2298.3.2 DNA Microarray-based Methods 2328.3.3 DNA Sequencing 234References 2369 Pharmacogenetics/Pharmacogenomics 2399.1 Uptake and Transport of Drugs 2429.2 Drug Metabolism 2429.2.1 Cytochrome P450 Enzymes 2439.2.2 Other Drug-metabolizing Enzymes 2469.3 Drug Targeting 2479.4 Drug Toxicity and Hypersensitivity 2509.5 Drug Development and Individual Pharmacotherapy 250References 25210 Recombinant Protein Drugs 25510.1 Production of Recombinant Proteins 25810.1.1 Bacteria 25910.1.2 Yeast and Other Fungi 26010.1.3 Insect Cells 26110.1.4 Mammalian Cells 26110.1.5 Transgenic Animals and Plants 26210.2 Classes of Recombinant Drugs 26410.2.1 Monoclonal Antibodies 26510.2.2 Hormones 27210.2.3 Growth Factors 27510.2.4 Fusion Proteins 27710.2.5 Cytokines 27810.2.6 Blood Coagulation Factors: Anticoagulants and Thrombolytics 27910.2.7 Therapeutic Enzymes 28110.2.8 Recombinant Vaccines 282References 28311 Gene Therapy 28711.1 Types of Gene Therapy 28811.2 Methods of Gene Transfer 28911.2.1 Retroviral Vectors 29011.2.2 Adenoviral Vectors 29211.2.3 Adeno-associated Virus Vectors 29311.2.4 Nonviral Gene Transfer 29511.3 Tissue Specificity of Gene Transfer and Gene Expression 29711.4 Applications of Gene Therapy 30011.4.1 Gene Therapy of Monogenic Diseases 30011.4.2 Gene Therapy of Cancer 30311.4.3 Other Diseases 30511.5 Genome Editing with CRISPR/Cas 30511.6 Future Prospects 309References 30912 Stem Cells 31312.1 Embryonic Stem Cells 31512.1.1 Generation and Properties of Embryonic Stem Cells 31512.1.2 Therapeutic Cloning 31712.2 Adult Stem Cells 31812.3 Induced Pluripotent Stem Cells 32012.3.1 Generation of Induced Pluripotent Stem Cells 32012.3.2 Properties of Induced Pluripotent Stem Cells 32312.4 Transdifferentiation and Direct Reprogramming 32312.5 Differentiation of Stem Cells 32512.6 Medical Applications of Stem Cells 32812.6.1 Adult Stem Cell Therapies 32812.6.2 Pluripotent Stem Cells for Biomedical Research 33012.6.3 Therapeutic Applications of Pluripotent Stem Cells 33312.6.3.1 Applications in the Central Nervous System 33412.6.3.2 Applications in the Eye 33512.6.3.3 Diabetes 33512.6.3.4 Heart Disease 33612.6.3.5 Combinations of Stem Cell and Gene Therapy 337References 33813 Oligonucleotide-based Strategies 34113.1 Antisense Oligonucleotides (ASOs) and Ribozymes 34313.1.1 Mechanism of Action of ASOs 34413.1.2 Development and Stabilization of ASO 34513.1.3 Clinical Applications of ASO 34713.1.4 Ribozymes 35013.2 RNA Interference 35113.2.1 Mechanism of RNAi 35213.2.2 Nonspecific Side Effects 35513.2.3 Stabilization and Delivery 35613.2.4 Research and Preclinical Applications of RNAi 35713.2.5 Clinical Applications of RNAi 35813.3 MicroRNAs 36113.3.1 The Biology of MicroRNAs 36113.3.2 MicroRNAs and Disease 36313.3.3 MicroRNA-Based Drugs in Clinical Development 36613.4 Aptamers, Decoy Oligonucleotides, and Immunostimulatory Oligonucleotides 36713.4.1 Aptamers 36813.4.1.1 Selection of Aptamers 36813.4.1.2 Modifications of Aptamers 37113.4.1.3 Clinical Development of Aptamers 37313.4.2 Decoy Oligonucleotides 37513.4.3 Immunostimulatory Oligonucleotides 376References 37714 Ethics in Molecular Medicine 38314.1 The Basis of Bioethics 38414.2 Fields of Application 38614.2.1 Genetic Testing and the “Right Not to Know” 38614.2.2 Stem Cell Research 38814.2.3 Preimplantation Genetic Diagnosis 39014.2.4 Animal Experimentation 393Abbreviations 399Glossary 405Index 409