Adenoviral Vectors for Gene Therapy
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Table of contents
- Contentsv
- Contributorsxxiii
- Prefacexxvii
- Chapter 1. Adenovirus Structure1
- I. Introduction1
- II. Molecular Composition2
- III. Structure of the Intact Virion3
- IV. Structure of the Capsid Components4
- V. Core Structure12
- VI. Adenovirus Protease12
- VII. Summary13
- References14
- Chapter 2. Biology of Adenovirus Cell Entry19
- I. Pathway of Adenovirus Cell Entry19
- II. Cell Receptors Involved in Attachment21
- III. Adenovirus Internalization Receptors24
- IV. Virus-Mediated Endosome Disruption and Uncoating29
- V. Beyond the Endosome: Trafficking of Viral Capsids and Import of Viral DNA into the Nucleus30
- VI. Conclusions31
- References32
- Chapter 3. Adenovirus Replication39
- I. Introduction39
- II. Classification40
- III. Genome Organization40
- IV. Virus Infection42
- V. Early Gene Expression42
- VI. Early Region 1A (El A)43
- VII. Early Region 1B (E1B)46
- VIII. Early Region 2 (E2)47
- IX. Early Region 3 (E3)49
- X. Early Region 4 (E4)52
- XI. Viral DNA Replication55
- XII. VA RNA Genes59
- XIII. Late Gene Expression and Virus Assembly59
- XIV. Vector Design62
- XV. Conclusion63
- References64
- Chapter 4. Adenoviral Vector Construction I: Mammalian Systems71
- I. Introduction71
- II. The Two-Plosmid Rescue System75
- III. Protocols for the Two-Plasmid Rescue System85
- References101
- Chapter 5. Adenoviral Vector Construction II: Bacterial Systems105
- I. Introduction105
- II. Generation of Ad: Traditional Approaches106
- III. Generation of Ad: Bacterial Systems107
- IV. Homologous Recombination in E. coli108
- V. Homologous Recombination with Linear Ad Vector Genome Plasmids109
- VI. Homologous Recombination with Circular Ad Vector Genome Plasmids116
- VII. Ad Vector Construction by Transposon-Mediated Recombination118
- VIII. Ad Vector Construction by in Vitro Ligation119
- IX. Conclusion121
- References123
- Chapter 6. Propagation of Adenoviral Vectors: Use of PER.C6 Cells129
- I. Introduction129
- II. Cells Expressing E1 of Adenovirus134
- III. PER.C6 Prevents RCA during Vector Production136
- IV. Production of Adenoviral Vectors141
- V. Safety Considerations of PER.C6146
- VI. Conclusions159
- References160
- Chapter 7. Purification of Adenovirus167
- I. Introduction167
- II. Recovery and Purification of Adenoviral Particles173
- III. Analytical Methods for Process Development and Process Tracking190
- IV. Formulation and Stability196
- V. Conclusions200
- References200
- Chapter 8. Targeted Adenoviral Vectors I: Transductional Targeting205
- I. Introduction205
- II. The Pathway of Adenoviral Infection206
- III. Strategies and Considerations207
- IV. Conjugate-Based Targeting209
- V. Genetic Targeting216
- VI. Transductionally Targeted Ad Vectors for Clinical Gene Therapy Applications232
- VII. Conclusion235
- References236
- Chapter 9. Targeted Adenoviral Vectors II: Transcriptional Targeting247
- I. Introduction: Rationale of Transcriptional Targeting247
- II. Regulation of Transcription in Eukaryotes248
- III. Approaches of Transcriptional Regulation256
- IV. Enhanced Control of Transgene Expression271
- V. Future Directions272
- VI. Summary274
- References275
- Chapter 10. Development of Attenuated Replication Competent Adenoviruses (ARCAs) for the Treatment o287
- I. Introduction287
- II. ARCAs for Prostate Cancer: CV706 and CV787290
- III. Synergy of ARCA and Conventional Therapy298
- IV. Toxicity of Intravenously Administered ARCAs in the Absence or Presence of Docetaxel305
- V. Effects of Preexisting Adenovirus Antibody on Antitumor Activity and Immunoapheresis for Human Th308
- VI. Clinical Development of CV706 and CV787314
- VII. Summary318
- References319
- Chapter 11. Replication-Selective Oncolytic Adenovirus E1-Region Mutants: Virotherapy for Cancer329
- I. Introduction329
- II. Attributes of Replication-Selective Adenoviruses for Cancer Treatment332
- III. Biology of Human Adenovirus332
- IV. Mechanisms of Adenovirus-Mediated Cell Killing333
- V. Approaches to Optimizing Tumor-Selective Adenovirus Replication333
- VI. E1A–CR2 Region Deletion Mutants334
- VII. E1 B 55-kDa Gene Deletion Mutant: d/l 520335
- VIII. Clinical Trial Results with Replication-Competent Adenoviruses in Cancer Patients337
- IX. Results from Clinical Trials with d/1520 (Onyx-015 or CI-1042)340
- X. Clinical Trial Results with d/1520 (Onyx-015): Summary343
- XI. Future Directions: Why Has d/1520 (Onyx-015) Failed to Date as a Single Agent?344
- XII. Improving the Efficacy of Replication-Selective Oncolytic Adenoviral Agents345
- XIII. Summary345
- References346
- Chapter 12. Innate Immune Responses to in Vivo Adenovirus Infection349
- I. Overview: Components of Innate Immunity349
- II. Distribution and Clearance of Adenovirus from the Respiratory Tract354
- III. Molecular Mediators of Inflammation359
- IV. Inflammatory Cell Recruitment364
- V. Innate Immunity and Programming of Adaptive Responses367
- VI. Innate Immunity and in Vivo Gene Therapy368
- VII. Future Directions369
- References369
- Chapter 13. Humoral Immune Response375
- I. Introduction375
- II. Adenovirus Structure and Serotype376
- III. Host Response to Gene Therapy Vectors381
- IV. Strategies to Overcome the Humoral Immune Response384
- V. Factors Modulating Host Responses to Gene Transfer Vectors390
- VI. Immune Response to Adenoviral–based Vectors in Humans396
- VII. Conclusion398
- References399
- Chapter 14. Novel Methods to Eliminate the Immune Response to Adenovirus Gene Therapy409
- I. Introduction409
- II. Immune Suppression410
- III. Immune Modulation411
- IV. Treatment with Soluble TNFRl to Eliminate Ad Inflammation in Lung and Liver414
- V. Inhibition of Cell Cytolysis Which Combines Treatment with Soluble DR5, Soluble Fas, and Soluble415
- VI. Immune Privilege417
- VII. APC-AdFasL Prolongs Transgene Expression and Specifically Minimizes T-Cell Response419
- VIII. Production of AdsTACI Prolongs Gene Expression and Minimizes B-Cell Response421
- IX. Summary423
- References424
- Chapter 15. High-Capacity ''Gutless'' Adenoviral Vectors: Technical Aspects and Applications429
- I. Introduction429
- II. Technical Aspects430
- III. Applications435
- IV. Conclusion442
- References442
- Chapter 16. Xenogenic Adenoviral Vectors447
- I. Impetus and Rationale447
- II. Classification of Adenoviruses447
- III. Factors Affecting Vector Design and Utility448
- IV. Utility of Xenogenic Vectors460
- V. Biosafety466
- VI. Vector Production and Purification469
- References470
- Chapter 17. Hybrid Adenoviral Vectors481
- I. Introduction481
- II. Hybrid Viral Vectors492
- III. Hybrid Adenoviral Vector Systems494
- IV. Conclusion518
- References524
- Chapter 18. Utility of Adenoviral Vectors in Animal Models of Human Disease I: Cancer533
- I. Introduction533
- II. Animal Models of Lung Cancer535
- III. Animal Models of Human Prostate Cancer547
- IV. Summary and Discussion551
- References553
- Chapter 19. Utility of Adenoviral Vectors in Animal Models of Human Disease II: Genetic Disease565
- I. Introduction565
- II. Pathophysiology of Cystic Fibrosis (CF) Lung Disease566
- III. Trials and Tribulations with Adenoviral Vectors for CF Lung Disease567
- IV. The Airway Epithelium: Cellular Targets for CF Gene Therapy568
- V. Adenoviral Vectors as Gene Transfer Vectors in the Lung570
- VI. Other Vectors585
- VII. Conclusion586
- References586
- Chapter 20. Utility of Adenoviral Vectors in Animal Models of Human Disease III: Acquired Diseases595
- I. Adenoviral Vectors for Infectious Disease595
- II. Chronic Inflammatory Diseases603
- III. Conclusions608
- References608
- Chapter 21. Testing of Adenoviral Vector Gene Transfer Products: FDA Expectations615
- I. Introduction615
- II. Manufacturing Control and Product Characterization616
- III. Developnnent of Recommendations for the Manufacture and Characterization of Adenoviral Vectors618
- IV. Considerations in Manufacturing Adenoviral Vectors620
- V. Process Controls621
- VI. Characterization of Adenoviral Vector Production Intermediates623
- VII. Characterization of Adenoviral Vector Final Products628
- VIII. Preclinical Testing of Adenoviral Vectors630
- IX. Toxicology Testing632
- X. Biodistribution636
- XI. Introduction to Clinical Testing637
- XII. Good Clinical Practices639
- XIII. Clinical Safety of Adenoviral Vector Products642
- XIV. Bioactivity of Adenoviral Vector Products643
- XV. Clinical Efficacy of Adenoviral Vector Products644
- XVI. How the Role of FDA Regulators Has Changed Since September 1999646
- XVI. Summary651
- References652
- Chapter 22. Imaging Adenovirus-Mediated Gene Transfer655
- I. Introduction655
- II. What Information Is Provided by Imaging?656
- III. Scientific Basis for Imaging657
- IV. Imaging and Gene-Therapy Vectors663
- V. Gene-Therapy Vectors May Advance Molecular Imaging669
- VI. Conclusion671
- References671
- Color Plate Section679
Adenoviral Vectors for Gene Therapy provides detailed and comprehensive coverage of these important therapeutic agents. The topics covered in this book range 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, to regulatory issues which must be considered prior to the initiation of human clinical gene therapy trials. The broad scope of this unique volume provides the reader with a complete understanding of the development and use of adenoviral vectors.
Key Features
* Provides complete coverage of basic biology of adenoviruses, as well as the 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
Key Features
* Provides complete coverage of basic biology of adenoviruses, as well as the 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