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Adenoviral Vectors for Gene Therapy
 
 

Adenoviral Vectors for Gene Therapy, 2nd Edition

 
Adenoviral Vectors for Gene Therapy, 2nd Edition,David Curiel,ISBN9780128002766
 
 
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D Curiel   

Academic Press

9780128002766

9780128005101

868

229 X 152

This detailed, comprehensive, fully updated edition provides the latest coverage of the gene delivery vehicles that are based on the adenovirus that is emerging as an important tool in gene therapy, highlighting their potential uses for the treatment of disease that includes information on their construction, propagation, and purification of adenoviral vectors.

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Key Features

  • Provides complete coverage of the basic biology of adenoviruses, as well as their construction, propagation, and purification of adenoviral vectors
  • Introduces common strategies for the development of adenoviral vectors, along with cutting-edge methods for their improvement
  • Demonstrates noninvasive imaging of adenovirus-mediated gene transfer
  • Discusses utility of adenoviral vectors in animal disease models
  • Considers Federal Drug Administration regulations for human clinical trials

Description

Adenoviral Vectors for Gene Therapy, Second Edition provides detailed, comprehensive coverage of the gene delivery vehicles that are based on the adenovirus that is emerging as an important tool in gene therapy. These exciting new therapeutic agents have great potential for the treatment of disease, making gene therapy a fast-growing field for research.

This book presents topics ranging from the basic biology of adenoviruses, through the construction and purification of adenoviral vectors, cutting-edge vectorology, and the use of adenoviral vectors in preclinical animal models, with final consideration of the regulatory issues surrounding human clinical gene therapy trials. This broad scope of information provides a solid overview of the field, allowing the reader to gain a complete understanding of the development and use of adenoviral vectors.

Readership

This book is intended for the full range of potential users as it embodies a comprehensive overview of basic biology and practical applications. In addition, the increasing number of "translational" physician-scientists will find this a unique resource for understanding the clinical issues of applying adenoviral vectors.

David Curiel

David T. Curiel, M.D., Ph.D. is the Director of the Cancer Biology Division of the Department of Radiation Oncology at Washington University School of Medicine. Dr. Curiel graduated medical school at Emory University in 1982, where he also completed his internship and residency in Internal Medicine. Dr. Curiel’s scientific training includes tenureship at the National Institutes of Health in Bethesda, Maryland at the Pulmonary Branch of the Heart and Lung, and Blood Institute (NHLBI) from 1985-1989, and a fellowship in Biotechnology at the National Cancer Institute, Navy Medical Oncology Branch from 1989-1990. He received his Ph.D. from University of Groningen in The Netherlands in 2002. Dr. Curiel has been at Washington University School of Medicine since 2011. In addition to his role as Director of the Cancer Biology Division, he is Director of the Biologic Therapeutics Center.

Affiliations and Expertise

Washington University School of Medicine, St. Louis, MO, USA

View additional works by David T. Curiel

Adenoviral Vectors for Gene Therapy, 2nd Edition

  • 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
  • 2. Biology of Adenovirus Cell Entry: Receptors, Pathways, Mechanisms
    • 1. Introduction
    • 2. Entry Pathways: Impact of Capsid Proteins
    • 3. Attachment Factors and Signaling Receptors
    • 4. Endocytosis
    • 5. Endosomal Escape
    • 6. Targeting the Nucleus
    • 7. Conclusions and Perspectives
  • 3. Adenovirus Replication
    • 1. Introduction
    • 2. Classification
    • 3. Adenovirus Genome Organization
    • 4. Virus Infection
    • 5. Early Gene Expression
    • 6. Viral DNA Replication
    • 7. Virus-Associated RNA Genes
    • 8. Late Gene Expression
    • 9. Viral DNA Packaging
    • 10. Conclusion
  • 4. Adenoviral Vector Construction I: Mammalian Systems
    • 1. Introduction
    • 2. Cell Lines for Propagating Adenovirus Vectors
    • 3. Construction of First-Generation Adenoviral Vectors
    • 4. Steps Involved in Adenovirus Vector Construction
    • 5. High-Efficiency Construction of Adenovirus Vectors for Generating Adenovirus-Based cDNA Expression Libraries
    • 6. Conclusion
  • 5. Adenoviral Vector Construction II: Bacterial Systems
    • 1. Introduction
    • 2. Construction of First Generation Adenovirus Vectors
    • 3. Construction of the E1/E3-Substituted Adenovirus Vectors
    • 4. Construction of Capsid-Mutant Adenovirus Vectors
    • 5. Construction of Small-Interfering RNA-Expressing Adenovirus Vectors
    • 6. Conclusion
  • 6. Upstream Bioprocess for Adenovirus Vectors
    • 1. Adenovirus Biology
    • 2. Manufacturing of Adenovirus Vectors for Gene Therapy
    • 3. Concerns in the Manufacturing of Adenovirus Vectors for Clinical Product Release
    • 4. Conclusion and Future Directions in Adenovirus
  • 7. Propagation of Adenoviral Vectors: Use of PER.C6™ Cells
    • 1. Introduction
    • 2. Cells Expressing E1 of Adenovirus
    • 3. PER.C6™ Prevents RCA during Vector Production
    • 4. Production of Adenoviral Vectors
    • 5. Safety Considerations of PER.C6™
    • 6. Conclusions
  • 8. Purification of Adenovirus
    • 1. Introduction
    • 2. Recovery and Purification of Adenoviral Particles
    • 3. Analytical Methods for Process Development and Process Tracking
    • 4. Formulation and Stability
    • 5. Conclusions
  • 9. Targeted Adenoviral Vectors I: Transductional Targeting
    • 1. Introduction
    • 2. Adapter-Mediated Ad Vector Targeting Approach
    • 3. Recombinant Ad Targeting Adapters
    • 4. Adenovirus Targeting Using Genetic Modification of Capsid Proteins
    • 5. Employment of Chimeric and Mosaic Fibers
    • 6. Employment of Targeting Peptides in Fiber Modification
    • 7. Employment of Alternative Capsid Sites for Ligand Incorporation
    • 8. Conclusion
  • 10. Targeted Adenoviral Vectors III: Transcriptional Targeting
    • 1. Introduction—Rationale of Transcriptional Targeting
    • 2. Regulation of Transcription in Eukaryotes
    • 3. Approaches of Transcriptional Regulation
    • 4. Enhanced Control of Transgene Expression
    • 5. Future Directions
    • 6. Summary
  • 11. Adenoviral Vector Targeting via Mitigation of Liver Sequestration
    • 1. Introduction
  • 12. Molecular Design of Oncolytic Adenoviruses
    • 1. Introduction
    • 2. Genetic Modifications to Achieve Tumor-Selective Replication
    • 3. Genetic Modifications to Enhance Oncolytic Potency
    • 4. Modification of Capsid Proteins to Achieve Tumor Targeting, Enhance Infectivity, and Display Antigens
  • 13. Conditionally Replicative Adenoviruses—Clinical Trials
    • 1. Origins of Cancer Virotherapy
    • 2. Oncolytic Adenoviruses: The dl1520 and H1011 Concept
    • 3. Delta-24
    • 4. Delta-24-RGD
    • 5. Clinical Experience with Delta-24-RGD
    • 6. Delta-24-RGD and Antitumor Immune Response
    • 7. ICOVIR Platform
    • 8. Clinical Experience with ICOVIR Viruses
    • 9. Conclusions and Future Directions
    • Conflict of Interest
  • 14. Innate Immune Response to Adenovirus Vector Administration In Vivo
    • 1. Adenovirus Interactions with Blood Cells and Components of Plasma
    • 2. Adenovirus Interactions in the Liver
    • 3. Adenovirus Interactions in the Spleen
    • 4. Adenovirus Interactions in the Lungs
  • 15. Antibodies against Adenoviruses
    • 1. Introduction
    • 2. Mechanisms of Antibody Action
    • 3. Consequences of Anti-Adenoviral Antibodies In Vivo
    • 4. Evading Antibodies
    • 5. Future Directions
  • 16. Methods to Mitigate Immune Responses to Adenoviral Vectors
    • 1. Introduction
    • 2. Activation of Innate and Adaptive Immunity by Adenovirus Vectors
    • 3. Therapeutic Strategies for Overcoming Immune Barriers to Adenovirus Vectors
    • 4. Concluding Remarks
  • 17. Helper-Dependent Adenoviral Vectors
    • 1. Introduction
    • 2. Production of Helper-Dependent Adenoviral Vectors
    • 3. Intracellular Status of Helper-Dependent Adenoviral Vectors
    • 4. Helper-Dependent Adenoviral Vectors as a Platform for Hybrid Vectors
    • 5. Liver Gene Therapy
    • 6. Brain and Eye Gene Therapy
    • 7. Lung Gene Therapy
    • 8. Muscle Gene Therapy
    • 9. Helper-Dependent Adenoviral Vectors as Genetic Vaccines
    • 10. Helper-Dependent Adenoviral Vectors and Stem Cells
    • 11. Human Gene Therapy with Helper-Dependent Adenoviral Vectors
    • 12. Concluding Remarks
  • 18. Hybrid Adenoviral Vectors
    • 1. Introduction
    • 2. Hybrid Viral Vectors
    • 3. Hybrid Adenoviral Vector Systems
    • 4. Conclusion
  • 19. Xenogenic Adenoviral Vectors
    • 1. Introduction
    • 2. Advantages of Adenovirus Vectors
    • 3. Preexisting Adenovirus Immunity
    • 4. Nonhuman Adenovirus Vectors
    • 5. Concluding Remarks
  • 20. Engineering Chimeric Adenoviruses: Exploiting Virus Diversity for Improved Vectors, Vaccines, and Oncolytics
    • 1. Bedside to Bench: Viral Chimerism as a Tool for Addressing Challenges of Adenovirus-Based Therapeutics and Vaccines
    • 2. General Strategies for Engineering of Chimeric Ad Capsids
    • 3. Chimeric Ad Capsids for Evasion of Neutralizing Antibodies
    • 4. Chimeric Ad Capsids for Improved Viral Biodistribution: Evasion of Blood Coagulation and Innate Immune Factors
    • 5. Chimeric Ad Capsids for Improved Viral Cell Binding and Entry
    • 6. Beyond the Capsid: Chimerism of Regulatory Proteins and Genomic Elements by Rational Engineering or Directed Evolution
    • 7. Chimeras of Ads and Viruses of Other Families for Delivery of Viral Genomes
    • 8. Combining Ad Chimerism with Other Virus Engineering Strategies
    • 9. Future Perspectives
  • 21. Adenoviral Vector Vaccines Antigen Transgene
    • 1. Introduction
    • 2. Characteristics of Adenoviruses
    • 3. Characteristics and Construction of Adenovirus Vectors
    • 4. Preexisting Immunity to Antigen of Adenoviruses
    • 5. Innate Immune Responses to Adenovirus Vectors
    • 6. Humoral Immune Responses to Adenoviral Vectors
    • 7. Cellular Immune Responses to Adenoviral Vectors
    • 8. Clinical Experience with Vaccines Based on Adenoviral Vector
  • 22. Adenoviral Vectors Vaccine: Capsid Incorporation of Antigen
    • 1. Introduction
    • 2. Fiber
    • 3. Penton Base
    • 4. Protein IX
    • 5. Hexon
    • 6. Conclusion
  • 23. Utility of Adenoviral Vectors in Animal Models of Human Disease I: Cancer
    • 1. Introduction
    • 2. Animal Models of Lung Cancer
    • 3. Animal Models of Human Prostate Cancer
    • 4. Summary and Discussion
  • 24. In Situ Vaccination with Adenoviral Vectors to Treat Cancer
    • 1. Vaccination Strategies and the Advantages of In Situ Vaccination with Adenovirus
    • 2. Adenovirus as an Immune Stimulant
    • 3. Adenoviral (HSV.tk)
    • 4. Ad.IFN
    • 5. Use of Combination Therapies to Augment In Situ Vaccination with Ad
    • 6. Conclusions and Future Directions
  • 25. Utility of Adenoviral Vectors in Animal Models of Human Disease II: Genetic Disease
    • 1. Introduction
    • 2. Pathophysiology of CF Lung Disease
    • 3. Trials and Tribulations with Ad Vectors for CF Lung Disease
    • 4. The Airway Epithelium: Cellular Targets for CF Gene Therapy
    • 5. Ad Vectors as Gene Transfer Vectors in the Lung
    • 6. Other Vectors
    • 7. Conclusion
  • 26. Adenoviral Vectors for Pulmonary Disease (Pulmonary Vascular Disease)
  • 27. Utility of Adenoviral Vectors in Animal Models of Human Disease III: Acquired Diseases
    • 1. Adenoviral Vectors for Infectious Disease
    • 2. Chronic Inflammatory Diseases
    • 3. Conclusions
  • 28. Animal Models of Gene Therapy for Cardiovascular Disease
    • 1. Introduction
    • 2. Adenoviral Vectors for Cardiovascular Gene Therapy
    • 3. Animal Models for Cardiovascular Gene Transfer
    • 4. Conclusions
  • 29. Polymer-Anchored Adenovirus as a Therapeutic Agent for Cancer Gene Therapy
    • 1. Introduction
    • 2. Polymer Coating on Adenovirus Surface
    • 3. Active Targeting-Mediated Smart Ad Nanohybrid Systems
    • 4. Biocompatible Hydrogels for Ad Depot System
    • 5. Conclusion
  • 30. Adenoviral Vectors for RNAi Delivery
    • 1. Introduction
    • 2. MicroRNAs and Human Diseases
    • 3. MicroRNA Biogenesis and Gene Silencing
    • 4. Posttranscriptional Gene Silencing by ncRNAs
    • 5. Adenovirus Vectors for ncRNA Gene Delivery
    • 6. In Vivo Delivery of ncRNAs Using Adenoviral Vectors
    • 7. MicroRNA-Mediated Regulation of Adenovirus Vector Tropism
    • 8. Adenoviral Virus-Associated RNAs and Their Biogenesis
    • 9. Inactivation of Protein Kinase R by VAI RNA
    • 10. Virus-Associated I RNA as an RNAi Inhibitor
    • 11. Virus-Associated II RNA
    • 12. Virus-Associated–Deleted HAdV Vectors for RNAi Analysis
    • 13. Adenovirus Full-Length VA RNAs and VA RNA-Derived miRNAs Suppress Cellular Gene Expression
    • 14. The PKR Pathway Rather than the RNAi Pathway Is Critical for Productive Infection
    • 15. Conclusions and Future Directions
  • 31. Imaging and Adenoviral Gene Therapy
    • 1. Introduction
    • 2. Review of Imaging Modalities
    • 3. What Information Is Provided by Imaging?
    • 4. Imaging to Monitor Gene Therapy
    • 5. Imaging and Gene Therapy Vectors
    • 6. Conclusions
  • 32. Regulation of Adenoviral Vector-Based Therapies: An FDA Perspective
    • 1. Introduction
    • 2. Regulatory Considerations in the Design of Adenoviral Vector-Based Therapies
    • 3. Chemistry, Manufacturing, and Control Requirements
    • 4. Manufacturing Control
    • 5. Preclinical Evaluation of Adenoviral Vector-Based Therapies
    • 6. Introduction to Clinical Testing
    • 7. Sponsor Outreach and Education
  • Index
 
 
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