Gene Therapy (eBook)

Front Cover 1
Gene Therapy 4
Copyright Page 5
Contents 6
Contributors 14
Chapter 1. Advances in Understanding the Pharmacological Properties of Antisense Oligonucleotides 18
I. Introduction 18
II. History 19
III. Proof of Mechanism 20
IV. Molecular Mechanisms of Antisense Drugs 24
V. Characteristics of Phosphorothioate Oligodeoxynucleotides 30
VI. The Medicinal Chemistry of Oligonucleotides 48
VII. Conclusions 55
References 55
Chapter 2. Targeted Tumor Cytotoxicity Mediated by Intracellular Single-Chain Anti-oncogene Antibodies 68
Text 68
References 97
Chapter 3. In Vivo Gene Therapy with Adeno-Associated Virus Vectors for Cystic Fibrosis 102
I. The Problem of Gene Therapy for Cystic Fibrosis Lung Disease 102
II. Adeno-Associated Virus as a Potential Vector System for Cystic Fibrosis Gene Therapy 105
III. Adeno-Associated Virus Vector Transduction of Cystic Fibrosis Bronchial Epithelial Cells and Complementation of the Cystic Fibrosis Defect 108
IV. In Vivo Gene Transfer with AAV–CFTR in the Bronchial Epithelium 111
V. Effects of Cell Proliferation on Expression from Adeno-Associated Virus Vectors 113
VI. Clinical Trials of AAV–CFTR Gene Transfer in Humans 114
References 114
Chapter 4. Engineering Herpes Simplex Virus Vectors for Human Gene Therapy 120
I. Introduction 120
II. Structure of the Herpes Simplex Virus Particle, Its Genome Organization, and Its Lytic Replication Cycle 124
III. Herpes Simplex Virus Cytotoxicity and the Complementation of Deletion Mutants 128
IV. Herpes Simplex Virus Amplicon Vectors 134
V. Herpes Simplex Virus Immunology and Antigenic Stealthing 137
VI. Alteration of the Viral Host Range and Vector Targeting 138
VII. The Herpes Simplex Virus Latency-Associated Transcript Promoter System and Its Utility in the Expression of Foreign Genes 139
VIII. Application of Herpes Simplex Virus Vectors 140
IX. Summary and Future Directions 145
References 146
Chapter 5. Human Adenovirus Vectors for Gene Transfer into Mammalian Cells 156
I. The Structure and Lytic Cycle of Adenovirus 157
II. Recombinant Adenovirus Vector Construction 160
III. Expression of Foreign DNA Sequences in Adenovirus Vectors 175
IV. Gene Therapy with Adenovirus Vectors 179
V. Conclusions 202
References 203
Chapter 6. Anti-oncogene Ribozymes for Cancer Gene Therapy 226
I. Introduction 226
II. Biochemistry of Ribozymes 228
III. Strategies for Designing Ribozymes 236
IV. Applications for Cancer Gene Therapy 240
V. Delivery Systems for Gene Therapy 249
VI. Clinical Applications 258
VII. Conclusion 259
References 260
Chapter 7. Cytokine Gene Transduction in the Immunotherapy of Cancer 278
I. Introduction and Background 278
II. Strategies and Techniques of Cytokine Gene Transfer 285
III. Active Immunogene Therapy 296
IV. Concluding Remarks 313
References 314
Chapter 8. Gene Therapy Approaches to Enhance Antitumor Immunity 328
I. Introduction 328
II. Gene Transfer of Immunostimulatory Cytokines 329
III. Antisense Inhibition of Immunosuppressive and Differentiation Factors 333
IV. Costimulatory Molecules and Antitumor Immunity 334
V. Genetic Modification of Tumor-Infiltrating Lymphocytes 334
VI. DNA Vaccines 336
VII. Clinical Cytokine Gene Therapy Experience 340
VIII. Clinical Trials of Immunogene Therapy Worldwide 351
References 351
Chapter 9. Modified Steroid Receptors and Steroid-Inducible Promoters as Genetic Switches for Gene Therapy 358
I. Overview 358
II. Structure of Eukaryotic Promoters and Regulation of Transcription 359
III. Nuclear Receptors and Signal Transduction 361
IV. Mechanisms of Action of Nuclear Receptors 362
V. Function of Natural and Synthetic Steroid-Responsive Promoters 370
VI. Uses of Modified Steroid-Inducible Expression Systems in Gene Therapy 376
VII. Conclusions 381
References 382
Chapter 10. Strategies for Approaching Retinoblastoma Tumor Suppressor Gene Therapy 388
I. Introduction 388
II. Basis for Considering the RB Tumor Suppressor Gene as a Therapeutic Target 390
III. RB Tumor Suppressor Gene Therapy in Animal Models: In Vivo Efficacy Tests 400
IV. Prospects for Emerging RB Tumor Suppressor Gene Therapy 406
References 409
Chapter 11. Immunoliposomes for Cancer Treatment 418
I. Introduction 418
II. Liposomes as a Drug Delivery System for Cancer Treatment 419
III. Antibodies Useful for Targeting 420
IV. Immunoliposome Design and Construction 423
V. Drug or Small-Molecule Delivery via Immunoliposomes 437
VI. Macromolecule Delivery via Immunoliposomes 440
VII. Nucleic Acid Delivery via Immunoliposomes 441
VIII. Conclusion 447
References 448
Chapter 12. Antisense Inhibition of Virus Infections 456
I. Introduction 456
II. Antisense Oligonucleotides as Potential Antiviral Agents 458
III. Oligonucleotides and Antiviral Activities 464
IV. Antisense RNA, RNA Decoys, and Ribozymes 489
V. Future Directions 492
References 493
Index 504
Contents of Previous Volumes 510