Adenoviral vectors for gene therapy / edited by David T. Curiel. -- 2nd ed. -- Amsterdam : Elsevier, c2016. – (63.499/A232/2nd ed.)

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

4. Endocytosis

5. Endosomal Escape

6. Targeting the Nucleus

7. Conclusions and Perspectives

Acknowledgments

References

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

References

4  Adenoviral Vector Construction h Mammalian Systems

l. 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

Acknowledgments

References

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

References

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

Acknowledgments

References

7  Propagation of Adenoviral Vectors: Use of PER.C6TM Cells

1. Introduction

2. Cells Expressing E1 of Adenovirus

3. PER.C6TM Prevents RCA during Vector Production

4. Production of Adenoviral Vectors

5. Safety Considerations of PER.C6TM

6. Conclusions

References

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

Acknowledgments

References

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

References

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

Acknowledgment

References

11  Adenoviral Vector Targeting via Mitigation of Liver Sequestration

1. Introduction

References

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

Acknowledgments

References

13  Conditionally Replicative Adenoviruses--Clinical Trials

1. Origins of Cancer Virotherapy

2. Oncolytic Adenoviruses: The d11520 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

Acknowledgments

References

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.

References

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

Acknowledgments

References

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

Acknowledgments

References

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

Acknowledgments

References

18  Hybrid Adenoviral Vectors

1. Introduction

2. Hybrid Viral Vectors

3. Hybrid Adenoviral Vector Systems

4. Conclusion

References

19  Xenogenic Adenoviral Vectors

1. Introduction

2. Advantages of Adenovirus Vectors

3. Preexisting Adenovirus Immunity

4. Nonhuman Adenovirus Vectors

5. Concluding Remarks

Acknowledgments

References

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

References

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

References

22  Adenoviral Vectors Vaccine: Capsid Incorporation of Antigen

1. Introduction

2. Fiber

3. Penton Base

4. Protein IX

5. Hexon

6. Conclusion

References

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

Acknowledgments

References

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

References

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

Acknowledgments

References

26  Adenoviral Vectors for Pulmonary Disease (Pulmonary Vascular Disease)

References

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

References

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

Acknowledgments

References

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

References

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

Acknowledgments

References

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

References

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

Acknowledgments

References

Index