Translating Gene Therapy to the Clinic

Techniques and Approaches

1st Edition - November 14, 2014
Editors: Jeffrey Laurence, Michael Franklin
Language: English
Hardback ISBN:
9 7 8 - 0 - 1 2 - 8 0 0 5 6 3 - 7
eBook ISBN:
9 7 8 - 0 - 1 2 - 8 0 0 5 6 4 - 4

Translating Gene Therapy to the Clinic, edited by Dr. Jeffrey Laurence and Michael Franklin, follows the recent, much-lauded special issue of Translational Research in emphasi… Read more

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Translating Gene Therapy to the Clinic, edited by Dr. Jeffrey Laurence and Michael Franklin, follows the recent, much-lauded special issue of Translational Research in emphasizing clinical milestones and critical barriers to further progress in the clinic. This comprehensive text provides a background for understanding the techniques involved in human gene therapy trials, and expands upon the disease-specific situations in which these new approaches currently have the greatest therapeutic application or potential, and those areas most in need of future research. It emphasizes methods, tools, and experimental approaches used by leaders in the field of translational gene therapy. The book promotes cross-disciplinary communication between the sub-specialties of medicine, and remains unified in theme.

Preface
About the Editors
Chapter 1. Translating Genome Engineering to Survival
- 1.1. Origins
- 1.2. Synchronicity of Discoveries
- 1.3. Gene Addition
- 1.4. From Gene Addition to Gene Editing
- 1.5. Therapy for Genetic Disorders
- 1.6. Roadmap to the Future
- Conflict of Interest
Chapter 2. Pluripotent Stem Cells and Gene Therapy
- 2.1. Genetic Approaches to Pluripotency
- 2.2. Transcription Factors Important for Reprogramming To Pluripotency
- 2.3. Methods for Genetic Reprogramming
- 2.4. Clinical Translation of IPSCS
- 2.5. Conclusion
Chapter 3. Genome Engineering for Therapeutic Applications
- 3.1. Introduction
- 3.2. Customizable DNA-Targeting Proteins
- 3.3. Genome Editing with Engineered Nucleases
- 3.4. Synthetic Transcription Factors for Therapeutic Applications
- 3.5. Conclusion
- Glossary
Chapter 4. Immune System Obstacles to In vivo Gene Transfer with Adeno-Associated Virus Vectors
- 4.1. Introduction
- 4.2. AAV Vectors
- 4.3. Innate Immunity in AAV Gene Transfer
- 4.4. T-Cell Responses to Vectors
- 4.5. Humoral Immunity
- 4.6. Conclusions
- Glossary
Chapter 5. Risks of Insertional Mutagenesis by DNA Transposons in Cancer Gene Therapy
- 5.1. Insertional Mutagenesis—the Downside of Gene Therapy?
- 5.2. Sleeping Beauty Transposon/Transposase System Adapted for Gene Therapy
- 5.3. Plasticity of Genomes and Gene Expression in Humans
- 5.4. Transposon-Mediated Gene Therapy in the Clinic
- 5.5. Conclusions
Chapter 6. Arthritis Gene Therapy: A Brief History and Perspective
- 6.1. Introduction
- 6.2. Conception and Strategies
- 6.3. Technology Development
- 6.4. Unresolved Issues
- 6.5. Clinical Trials
- 6.6. Veterinary Applications
- 6.7. Other Applications of Intra-Articular Gene Therapy
- 6.8. Commercialization
- 6.9. Perspectives
Chapter 7. Type 1 Diabetes Mellitus: Immune Modulation as a Prerequisite for Successful Gene Therapy Strategies
- 7.1. Introduction
- 7.2. Effective Immune Therapy/Modulation: A Prerequisite for Successful Gene Therapy of Type 1 Diabetes
- 7.3. Targeted Islet Antigen Recognition and Antigen-Based Therapies
- 7.4. Broad Immunosuppressive Therapies
- 7.5. Immunotherapies that Target Events in T Cell Response
- 7.6. Prospects for Immunotherapy in Protecting Neo-Beta Cells
- 7.7. Conclusion
Chapter 8. Gene Therapy for Diabetes
- 8.1. Introduction
- 8.2. Generation of β Cells from Pancreatic Mature Non-β Cells
- 8.3. Generation of β Cells from Tissue Progenitor Cells
- 8.4. Generation of β Cells from Stem Cells
- 8.5. Generation of New β Cells by Inducing Their Replication
- 8.6. Closing Remarks
Chapter 9. Gene Therapy for Neurological Diseases
- 9.1. Introduction
- 9.2. Viral Vectors for Neurological Diseases
- 9.3. Gene Therapy for Chronic Pain
- 9.4. Gene Therapy for Epilepsy
- 9.5. Parkinson’s Disease
- 9.6. Conclusions
Chapter 10. Genetic and Cell-Mediated Therapies for Duchenne Muscular Dystrophy
- 10.1. Introduction
- 10.2. Gene Replacement Therapies
- 10.3. Strategies Aimed at Correcting the Defective Dystrophin Gene
- 10.4. Cell-Based Therapies for DMD
- 10.5. Alternative Strategies to Restoration of Dystrophin Expression into Muscle
- 10.6. Conclusion
- Glossary
Chapter 11. Gene Therapy for Retinal Disease
- 11.1. Introduction to the Retina and Inherited Retinal Diseases
- 11.2. Cell-Specific Targeting within the Retina
- 11.3. Promoter Choice for Expression in Specific Retinal Cell Targets
- 11.4. AAV Treatment of Autosomal Recessive Models of Retinal Disease
- 11.5. AAV Treatment of Autosomal Dominant Models of Retinal Disease
- 11.6. AAV Delivery of Large Genes to the Retina
- 11.7. Neuroprotection of the Retina Using AAV
- 11.8. Human AAV Clinical Trials for the Treatment of IRD
- 11.9. Summary
Chapter 12. Gene Therapy for Hemoglobinopathies: Progress and Challenges
- 12.1. Why Gene Therapy for Hemoglobinopathies?
- 12.2. Challenges to Human gene Therapy for Hemoglobinopathies
- 12.3. Preclinical Studies in Animal Models and Human Cells
- 12.4. Targeted Reactivation of Fetal Hemoglobin
- 12.5. Clinical Trials for the Hemoglobinopathies
- 12.6. Genome Toxicity
- 12.7. Phenotypic Variability and Gene Transfer in Patients Affected by Hemoglobinopathies
- 12.8. Future Perspectives
- 12.9. Conclusion
Chapter 13. Hemophilia Gene Therapy
- 13.1. Introduction
- 13.2. Hemophilia B Gene Transfer
- 13.3. AAV and Hemophilia A
- 13.4. rAAV Dose and the Immune Response
- 13.5. AAV-Mediated Transfer Lasts a Long Time
- 13.6. Summary
Chapter 14. Gene Transfer for Clinical Congestive Heart Failure
- 14.1. Introduction
- 14.2. General Considerations for Cardiac Gene Transfer
- 14.3. Candidates for CHF Gene Transfer
- 14.4. Vectors and Methods for Cardiac Gene Transfer
- 14.5. Gene Transfer Clinical Trials for CHF
- 14.6. Conclusion
- Glossary
Chapter 15. Gene Therapy for the Prevention of Vein Graft Disease
- 15.1. Introduction to Vein Graft Disease
- 15.2. Pathophysiology of Vein Graft Disease
- 15.3. Gene Delivery Strategies
- 15.4. Animal Models of Vein Graft Disease
- 15.5. Gene Targets and Preclinical Studies
- 15.6. The PREVENT Trials
- 15.7. Additional Considerations for Translation
- 15.8. Conclusions
Chapter 16. Gene Therapy in Cystic Fibrosis
- 16.1. A Brief History of Cystic Fibrosis Genetics
- 16.2. CFTR Mutations
- 16.3. CF Gene Therapy Challenges
- 16.4. CF Gene Therapy in Clinical Trials
- 16.5. Mutant Protein Repair
- 16.6. Conclusion
- Glossary
Chapter 17. Genetic Engineering of Oncolytic Viruses for Cancer Therapy
- 17.1. Introduction
- 17.2. Conditionally Replicating Adenoviruses (CRADs)
- 17.3. Herpes Simplex Virus (HSV)
- 17.4. Vaccinia Virus (VV)
- 17.5. Reovirus Type 3 Dearing (RT3D or Reolysin^®)
- 17.6. Vaccine Strains of Measles Virus (vMV)
- 17.7. Vesicular Stomatitis Virus (VSV)
- 17.8. Challenges to Oncolytic Virotherapy
- 17.9. Conclusions and Future Directions
Chapter 18. T Cell-Based Gene Therapy of Cancer
- 18.1. Introduction: T Cell-Based Immunotherapy
- 18.2. Ex vivo T Cell Expansion
- 18.3. Modification Strategies for T Cell Redirection
- 18.4. Approaches to Enhance T Cell Activity
- 18.5. Mitigation of Adverse Events and Safety Considerations
- 18.6. Translation of Engineered T Cell Therapy to the Clinic
- 18.7. Conclusions and Future Directions
- Disclosure of Potential Conflicts of Interest
- Glossary
Chapter 19. Current Status of Gene Therapy for Brain Tumors
- 19.1. Introduction
- 19.2. Gene Delivery Vehicles for Brain Tumors
- 19.3. Gene Therapy Strategies for Brain Tumors
- 19.4. Status of Clinical Trials for GBM
- 19.5. Current Challenges and Future Directions
Index

Life Sciences

Physical Sciences & Engineering

Social Sciences & Humanities

Health