Kooperativer Bibliotheksverbund

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Umfang: 1 online resource (870 pages) : , illustrations

Ausgabe: Second edition.

ISBN: 0-12-800276-X , 0-12-800510-6

Anmerkung: Front Cover -- Adenoviral Vectors for Gene Therapy -- Adenoviral Vectors for Gene Therapy -- Copyright -- Contents -- List of Contributors -- 1 - Adenovirus Structure -- 1. Historical Perspective on Adenovirus Structure -- 2. Hexon Structure and Capsid Packing -- 3. Penton Base Structure and Integrin-Binding RGD Loop -- 4. Fiber Structure and Receptor Interactions -- 5. Atomic Resolution Cryo-Electron Microscopy and X-ray Crystallographic Adenovirus Structures -- 6. Hexons in the Atomic Resolution Adenovirus Structures -- 7. Conformational Differences of the Penton Base in the Atomic Resolution Adenovirus Structures -- 8. Alternate Assignments for the Four-Helix Coiled Coil -- 9. Protein IIIa Structure -- 10. Protein IX Structure -- 11. Core Protein V Structure -- 12. Protein VI Structure -- 13. Protein VIII Structure -- 14. Adenovirus Protease -- 15. Concluding Remarks -- References -- 2 - Biology of Adenovirus Cell Entry: Receptors, Pathways, Mechanisms -- 1. Introduction -- 2. Entry Pathways: Impact of Capsid Proteins -- 3. Attachment Factors and Signaling Receptors -- 3.1 Accessing the CAR -- 3.2 Using CD46 in High- and Low-Affinity Modes -- 3.3 Desmoglein-2 -- 3.4 Sialic Acid -- 3.5 Heparan Sulfate -- 3.6 Scavenger Receptors and Other Attachment Factors -- 3.7 Internalization Co-receptors: Integrins -- 3.8 Extracellular Factors Influencing Viral Tropism -- 3.8.1 Coagulation Factors -- 3.8.2 Immunoglobulins and Complement -- 3.8.3 Lactoferrin -- 3.8.4 Dipalmitoylphosphatidylcholine -- 4. Endocytosis -- 4.1 Clathrin-Mediated Endocytosis -- 4.2 Macropinocytosis -- 4.3 Phagocytosis -- 4.4 Caveolar Endocytosis -- 5. Endosomal Escape -- 5.1 Protein VI for Membrane Lysis -- 5.2 A New Concept: Hijacking Membrane Repair for Endosome Lysis -- 6. Targeting the Nucleus -- 6.1 Transport through the Cytoplasm. , 6.2 Deoxyribonucleic Acid Uncoating and Nuclear Import -- 7. Conclusions and Perspectives -- Acknowledgments -- References -- 3 - Adenovirus Replication -- 1. Introduction -- 2. Classification -- 3. Adenovirus Genome Organization -- 4. Virus Infection -- 5. Early Gene Expression -- 5.1 Early Region 1A -- 5.2 Early Region 1B -- 5.3 Early Region 2 -- 5.4 Early Region 3 -- 5.5 Early Region 4 -- 6. Viral DNA Replication -- 7. Virus-Associated RNA Genes -- 8. Late Gene Expression -- 9. Viral DNA Packaging -- 10. Conclusion -- References -- 4 - Adenoviral Vector Construction I: Mammalian Systems -- 1. Introduction -- 1.1 Adenovirus Biology -- 1.2 Adenovirus Vectors -- 2. Cell Lines for Propagating Adenovirus Vectors -- 2.1 Propagation of Adenovirus Vectors Encoding Toxic Transgenes for Cancer Gene Therapy -- 3. Construction of First-Generation Adenoviral Vectors -- 3.1 Early Methods -- 3.2 The Two-Plasmid Rescue System -- 3.2.1 Development of the Two-Plasmid Rescue System -- 3.2.2 Fine-Tuning of the Two-Plasmid Rescue System -- 4. Steps Involved in Adenovirus Vector Construction -- 4.1 Preparation of Adenovirus Genomic and Shuttle Plasmid DNA for Cotransfection -- 4.2 Cotransfection of HEK-293 Cells with Genomic and Shuttle Plasmid -- 4.3 Analysis of the Rescued Recombinant Adenovirus Vectors -- 4.4 Plaque Purification of Recombinant Adenovirus Vector -- 4.5 Preparation of High-Titer Virus Stock (Crude Lysate) -- 4.5.1 Preparation of High-Titer Crude Virus Stocks from Monolayer Culture -- 4.5.2 Preparation of High-Titer Crude Virus Stocks from Suspension Culture -- 4.6 Purification of High-Titer Adenovirus Vector by CsCl Banding -- 4.7 Characterization of Adenovirus Vectors -- 4.7.1 Determination of Particles to Plaque-Forming Units Ratio -- 4.7.2 Replication-Competent Adenovirus Assay. , 5. High-Efficiency Construction of Adenovirus Vectors for Generating Adenovirus-Based cDNA Expression Libraries -- 6. Conclusion -- Acknowledgments -- References -- 5 - Adenoviral Vector Construction II: Bacterial Systems -- 1. Introduction -- 2. Construction of First Generation Adenovirus Vectors -- 2.1 Early Methods for Adenovirus Vector Construction -- 2.2 Homologous Recombination Method in Escherichia coli -- 2.3 Improved in vitro Ligation Method -- 2.4 Homologous Recombination Method in Yeast -- 2.5 Transposon-Mediated Recombination Method -- 2.6 Other Methods -- 3. Construction of the E1/E3-Substituted Adenovirus Vectors -- 4. Construction of Capsid-Mutant Adenovirus Vectors -- 4.1 Construction of Fiber-Mutant Adenovirus Vectors -- 4.2 Construction of Other Capsid Protein-Mutant Adenovirus Vectors -- 5. Construction of Small-Interfering RNA-Expressing Adenovirus Vectors -- 6. Conclusion -- References -- 6 - Upstream Bioprocess for Adenovirus Vectors -- 1. Adenovirus Biology -- 1.1 Structure and Genome -- 1.2 Infection and Replication Cycle -- 2. Manufacturing of Adenovirus Vectors for Gene Therapy -- 2.1. Adenovirus Vectors and Producer Cells -- 2.1.1 First-Generation Vectors -- 2.1.2 Conditionally Replicating Vectors -- 2.1.3 Second-Generation Vectors -- 2.1.4 Third-Generation Vectors -- 2.1.5 Novel Adenovirus Vectors -- 2.2 Upstream Process for Adenovirus Vectors -- 2.2.1 Cell Culture and Adenovirus Production Process -- 2.2.2 Adenovirus Seed Stocks -- 2.2.3 The Infection Process and Harvest Strategy -- 2.2.4 Productivity of Adenovirus Vector Manufacturing -- 2.2.5 Adenovirus Production at High Cell Density -- 2.2.6 Physical Parameters and Process Monitoring -- 2.3 Production Process for Helper-Dependent Vectors -- 2.4 Downstream Process for Adenovirus Vectors. , 3. Concerns in the Manufacturing of Adenovirus Vectors for Clinical Product Release -- 3.1 Extraneous Agents -- 3.2 Replication-Competent Adenovirus -- 3.3 Vector Genetic Stability -- 3.4 Quantity and Potency -- 4. Conclusion and Future Directions in Adenovirus -- Acknowledgments -- References -- 7 - Propagation of Adenoviral Vectors: Use of PER.C6™ Cells -- 1. Introduction -- 1.1 Scope of the Paper -- 1.2 Adenoviruses -- 1.3 Adenovirus Replication -- 2. Cells Expressing E1 of Adenovirus -- 2.1 Transformation of Cells by E1 of Adenovirus -- 2.2 E1 Expressing Cell Lines for Adenoviral Vector Production -- 3. PER.C6™ Prevents RCA during Vector Production -- 3.1 RCA -- 3.2 PER.C6™: Absence of Sequence Overlap Eliminates RCA Generation -- 3.2.1 E1 Construct Used for Making PER.C6™ -- 3.2.2 Generation of PER.C6™ -- 3.3 Frequency of RCA Occurrence -- 4. Production of Adenoviral Vectors -- 4.1 Vector Stability -- 4.2 The Production Process -- 4.3 Yields of Adenoviral Vectors -- 4.4 Scale of Adenoviral Vector Production -- 5. Safety Considerations of PER.C6™ -- 5.1 QC Testing of PER.C6™ Cells for Use in the Manufacture of Biologicals and Vaccines -- 5.1.1 QC Testing for the Release of PER.C6™ Master Cell Bank -- 5.1.2 QC Testing for the Release of a PER.C6™ Working Cell Bank -- 5.1.3 Development of a Master Cell Bank at the Merck Research Laboratories -- 5.2 Tumorigenicity -- 5.2.1 Tumorigenicity Studies of PER.C6™ Cells -- 5.2.2 Tumorigenicity Studies of Residual DNA from PER.C6™ Cells -- 5.2.3 Concerns About Using a Tumorigenic Cell Substrate -- 5.3 Prion-Related Issues -- 5.4 Genetic Characterization of PER.C6™ Cells -- 5.4.1 Sequence Analysis of E1 -- 5.4.2 Site of Integration of E1 -- 5.4.3 Copy Number of the E1 Construct -- 5.4.4 Chromosome Analysis -- 5.4.5 DNA Fingerprinting -- 6. Conclusions -- References -- 8 - Purification of Adenovirus. , 1. Introduction -- 1.1 Physical Characteristics of the Adenovirus Particle in Solution -- 1.1.1 Particle Size -- 1.1.2 Diffusion of Adenovirus Particles -- 1.1.3 Capsid Surface -- 1.1.4 Hydration of the Adenovirus Particle -- 1.2 Features of the Milieu -- 1.2.1 Culture Conditions -- 1.2.2 Construct-Induced Contaminants and Considerations -- 1.3 Summary of Characteristics -- 2. Recovery and Purification of Adenoviral Particles -- 2.1 Harvest Methods -- 2.2 Lysis Methods -- 2.2.1 Freeze Thaw -- 2.2.2 Homogenization -- 2.2.3 Sonication -- 2.2.4 Simultaneous Harvest and Lysis -- 2.2.5 Lysis during Filtration -- 2.2.6 Lysis with Detergent -- 2.3 Clarification -- 2.3.1 Centrifugation -- 2.3.2 Filtration -- 2.3.3 Expanded Bed Chromatography -- 2.3.4 Digestion of DNA -- 2.4 Purification -- 2.4.1 Ultracentrifugation -- 2.4.2 Purification by Chromatography -- 2.4.2.1 Ion Exchange Chromatography of Adenovirus -- 2.4.2.1.1 Disposable Ion-Exchange Membrane Absorber Disposable membrane absorbers (such as Mustang Q® from Pall Scientific and S... -- 2.4.2.2 Immobilized Metal Affinity Chromatography of Adenovirus -- 2.4.2.3 Reversed-Phase Chromatography -- 2.4.2.4 Hydrophobic Interaction Chromatography of Adenovirus -- 2.4.2.5 Size Exclusion Chromatography of Adenovirus -- 2.5 Buffer Exchange -- 3. Analytical Methods for Process Development and Process Tracking -- 3.1 Plaque-Forming Titer Assays -- 3.2 Adenovirus 96 Well Titer Plate Assay -- 3.2.1 Spearman-Karber Analysis -- 3.2.2 Diffusion-Normalized Calculation -- 3.3 Flow Cytometry -- 3.4 Particle Concentration Determination by Ultraviolet Absorbance -- 3.5 Analytical Reverse-Phase High-Performance Liquid Chromatography -- 3.6 Analytical Anion Exchange High-Performance Liquid Chromatography -- 4. Formulation and Stability -- 5. Conclusions -- Acknowledgments -- References. , 9 - Targeted Adenoviral Vectors I: Transductional Targeting.

Sprache: Englisch