Advanced Textbook on Gene Transfer, Gene Therapy and Genetic Pharmacology

The following sections are included:

• Dedication
• Preface
• Contents

Gene therapy offers unprecedented opportunities to treat or cure disease and alleviate human suffering. It has been more than ten years now since the first clinical successes in gene therapy were first reported for the treatment of severe combined immunodeficiency (SCID-X1). The recurrent opportunistic and life-threatening infections in patients suffering from these types of hereditary diseases are like a sword of Damocles that constantly reminds them of their tragic fate. The majority of the infants that were afflicted by this devastating disease and that were subsequently treated by gene therapy can now essentially lead normal lives. These remarkable and historic achievements formally prove that gene therapy, moving forward, can be a realistic and successful medical intervention. Most importantly, these successes offer new therapeutic options for patients who are currently untreatable…

The following sections are included:

• Definitions
• Critical Advantageous Properties of Gene Therapy
• Temporal Control of Gene Expression
• Strategies and Protocols for Gene Therapy and Genetic Pharmacology
• For Further Reading

The following sections are included:

• Historical Evolution
• Obstacles to the Development of Gene Therapy
• Significant Recent Progress in Gene Therapy
• The Example of Exon Skipping
• Concluding Remarks
• References

The following sections are included:

• Introduction
• Antigene Strategy
• Antisense Strategy
• Delivery Issues — Limitations and Perspectives
• Conclusion
• For Further Reading

The following sections are included:

• Introduction
• RNAi Trigger Types
• Toxicity
• RNA Polymerase III (Pol III) Promoter Types
• Specific Pol III Promoters
• RNA Polymerase II (Pol II) Promoters
• Conditional RNA Interference
• Multiplexing Strategies
• Conclusion
• References

The following sections are included:

• Introduction
• Coding Frame Restoration of a Mutated Gene by Exon Skipping
• mRNA Repair by Trans-Splicing Approaches
• Conclusion
• Acknowledgments
• References

The following sections are included:

• Introduction
• Cell and Gene Therapy
• Oligo/Polynucleotide-Mediated Sequence-Specific Modification
• Enhancement of Gene Targeting Efficacy
• Targeted Cleavage of Genomic DNA
• Recombinant-Virus-Mediated Gene Targeting
• Conclusion
• Acknowledgements
• References

The following sections are included:

• Introduction
• The Concept: Designing Retrovirus-Based Vectors
• Technology Developments to Overcome Bottlenecks and Improve Safety
• Applications
• Prospects
• References

The following sections are included:

• Introduction
• General Aspects of Adenovirus Biology
• First-Generation Adenovirus Vectors
• High-Capacity Adenovirus Vectors
• Conditionally Replicating Adenoviral Vectors
• Application of Adenoviral Vectors
• Recent Developments in Adenoviral Vector Technology
• For Further Reading

The following sections are included:

• Introduction
• Wild-Type AAV Biology
• Recombinant AAV Vectors
• References

The following sections are included:

• Introduction
• Short Introduction to HSV-1 Biology
• The Virus Particle
• The HSV-1 Genome
• Virus Gene Expression
• HSV-1-Based Vectors
• Concluding Remarks
• References

The following sections are included:

• Plasmids — Tools in Molecular Biology
• DNA Gene Transfer and Application
• Next Generation Plasmids and Transposons
• Minicircle DNA — “Plasmids” Without “Bits and Pieces”
• Acknowledgment
• References

The following sections are included:

• Multi-Functional Nucleic Acid Delivery Systems
• Role of the Carrier in the Delivery System
• Transport of Polyplexes Across the Plasma Membrane
• Design of Polyplexes for In Vivo Delivery
• Assembly, Disassembly and Testing of Macromolecular Conjugates
• Acknowledgements
• For Further Reading

The following sections are included:

• Lipid Self-Association and Self-Assembly
• Cationic Lipids to Cationic Liposomes/Micelles
• Characterization of the Interactions between Lipids and DNA
• DNA Delivery to Cells
• Delivery of pDNA in vivo
• Fundamentals of siRNA Delivery
• The Delivery of siRNA in vivo
• Conclusion: Next Steps in Therapeutic Nucleic Acid Delivery
• References

The following sections are included:

• Definition of Hydrodynamic-Pressure-Based Gene Delivery
• Fundamentals of Hydrodynamic Gene Delivery
• Image-Guided, Computer-Assisted Hydrodynamic Delivery for Site-Specific Gene Transfer in Large Animals
• Future Perspectives
• References

The following sections are included:

• History and Principles of Electrotransfer
• Animal Studies
• Clinical Applications
• References
• For Further Reading

The following sections are included:

• General Introduction
• Molecular Imaging of Gene Expression in the Live Subject: Basic Principles
• Imaging Modalities
• Preclinical Applications
• Clinical Studies
• Conclusions
• References

The following sections are included:

• Cancer and Oncolytic Adenoviruses
• Development of Oncolytic Adenoviruses
• Enhancing the Potency of Oncolytic Adenoviral Mutants
• Development of a New Generation of Oncolytic Mutants to Enhance Antitumor Efficacy
• Conclusions
• For Further Reading

The following sections are included:

• Introduction
• Prostate Cancer
• Melanoma
• Non-Hodgkin B-Cell Lymphoma
• Breast Cancer
• Concluding Remarks
• References

The following sections are included:

• The Beta-Hemoglobinopathies
• Erythroid-Specific and High-Level Expression of Globin Genes
• The Usefulness of Lentiviral Vectors
• Goals for the Gene Therapy of Beta-Thalassemia and Sickle Cell Disease
• Correction of Mouse Models of Beta-Thalassemia and Sickle Cell Disease
• Limited Expression Level Per Cell and Position Effect Variegation
• Genotoxic Potential of Lentiviral Vectors Expressing Globin Genes
• Transfusion Independence in a Beta-Thalassemic Patient Treated by Gene Therapy
• Lessons for Hematopoietic Gene Therapy
• References

The following sections are included:

• Hemophilia A and B
• Hemophilia as a Target for Gene Therapy
• Target Cells
• Gene Delivery Systems
• Perspectives
• Acknowledgements
• References

The following sections are included:

• Introduction
• The Eye, an Ideal Target for In Vivo Gene Transfer
• Vectors for Retinal Gene Transfer
• Inherited Retinal Degeneration: From Animal Models to Clinical Trials
• Future Directions: Generic Gene Therapy of the Retina
• Conclusion
• Acknowledgements
• References
• For Further Reading

The following sections are included:

• Considerations for Treating Diseases of the Central Nervous System
• CNS Delivery
• Therapeutic Strategies and Examples of Gene Therapy of Neurological Diseases
• Critical Issues
• Conclusions
• References
• For Further Reading

The following sections are included:

• Introduction
• Attractiveness of Muscle Tissue for Gene Therapy Approaches
• Genetic Pharmacology of the Mutated Dystrophin Pre-mRNA by Exon Skipping for Duchenne Muscular Dystrophy Treatment
• Microdystrophin and Myostatin Gene Therapy for Duchenne Muscular Dystrophy Using Adeno-Associated Virus Vectors, Gene Therapy: Administration of the Dystrophin Gene and/or of a Protein Inhibiting Myostatin
• References

The following sections are included:

• Pluripotent Stem Cells
• Reprogramming
• Genetic Modification of iPSCs
• Application of iPS Cells in Regenerative Medicine
• For Further Reading

The following sections are included:

• General Overview
• Adenoviral Vector Production and Purification
• Adeno-Associated Virus Vector Production and Purification
• Lentiviral Vector Production and Purification
• Biosafety of Viral Vector
• Perspectives
• References

The following sections are included:

• The Plasmid DNA Production Strain Escherichia coli
• Manufacturing Processes (“Kit or Service?”)
• Large-Scale Manufacturing of Plasmid DNA
• “Difficult sequences” in Plasmid DNA
• Quality and Regulatory Requirements
• Acknowledgement
• References

The following section is included:

• Index