Translating Gene Therapy to the Clinic - Techniques and Approaches

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Translating Gene Therapy to the Clinic: Techniques and Approaches

Copyright

Contents

Preface

REFERENCES

About the Editors

Contributors

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

ACKNOWLEDGMENTS

REFERENCES

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

REFERENCES

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

ACKNOWLEDGMENTS

REFERENCES

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

ACKNOWLEDGMENT

REFERENCES

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

ACKNOWLEDGMENT

REFERENCES

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

ACKNOWLEDGMENTS

REFERENCES

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

ACKNOWLEDGMENT

REFERENCES

Chapter 8 - Gene Therapy for Diabetes

LIST OF ABBREVIATIONS

8.1 INTRODUCTION

8.2 GENERATION OF . CELLS FROM PANCREATIC MATURE NON-. CELLS

8.3 GENERATION OF . CELLS FROM TISSUE PROGENITOR CELLS

8.4 GENERATION OF . CELLS FROM STEM CELLS

8.5 GENERATION OF NEW . CELLS BY INDUCING THEIR REPLICATION

8.6 CLOSING REMARKS

ACKNOWLEDGMENTS

REFERENCES

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

REFERENCES

Chapter 10 - Genetic and Cell-Mediated Therapies for Duchenne Muscular Dystrophy

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

ACKNOWLEDGMENTS

REFERENCES

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

REFERENCES

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

ACKNOWLEDGMENT

REFERENCES

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

REFERENCES

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

REFERENCES

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

REFERENCES

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

REFERENCES

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

ACKNOWLEDGMENTS

REFERENCES

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

REFERENCES

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

REFERENCES

Index