Verfügbarkeit: A guide to human gene therapy

A guide to human gene therapy:

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Format:	Buch
Sprache:	German
Veröffentlicht:	New Jersey [u.a.] World Scientific 2010
Schlagworte:	Gene therapy Gentherapie
Online-Zugang:	Inhaltsverzeichnis Klappentext
Beschreibung:	XXVI, 388 S. Ill., graph. Darst.
ISBN:	9789814280907 9814280909

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Datensatz im Suchindex

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adam_text	Contents Preface v Contributors xxiii 1. Non-Viral Gene Therapy 1 Sean M. Sullivan 1. Introduction ........................ 1 2. PlasmidDNA ....................... 3 2.1 Plasmid DNA Manufacture ............. 5 3. Plasmid DNA Gene Transfer Methods.......... 6 3 .1 Plasmid DNA or Naked DNA as a Gene Delivery System ....................... 6 3.1.1 Electroporation of Naked DNA....... 8 3.1.2 Sonoporation of Naked DNA........ 9 3.2 Plasmid DNA Formulations ............ 9 3.2.1 Cationic Lipids ............... 9 3.2.1.1 In vitro transfection ........ 10 3.2.1.2 Systemic in vivo gene transfer ... 11 3.2.1.3 Local administration of cationic lipid/pDNA transfection complexes ............. 12 3.3 Polymer ....................... 14 3.3.1 Cationic Polymers .............. 14 3.3.2 Neutral Polymer ............... 15 Conclusions ........................ 17 References ........................... 17 A Guide to Human Gene Therapy 2. Adenoviral Vectors 21 Stuart A. Nicklin and Andrew H. Baker 1. Introduction ........................ 21 2. Adenoviral Capsid Structure ............... 22 3. Adenoviral Cell Entry ................... 23 4. Production of Adenoviral Vectors ............. 24 5. Production of Targeted Adenoviral Vectors ........ 26 6. Gene Therapy Applications ................ 28 7. Immune Responses to Ad Vectors ............ 30 8. Safety and Regulatory Issues ............... 32 9. Conclusions ........................ 33 References ........................... 33 3. Retroviral Vectors and Integration Analysis 37 Cynthia C. Bartholomae, Romy Kirsten, Hanno Glimm, Manfred Schmidt and Christof von Kalle 1. Introduction ........................ 37 2. Design, Production and Mechanism of Transduction . . . 38 3. In vivo Application .................... 41 4. Side Effects in Retroviral Gene Therapy ......... 42 4.1 Distribution of Retroviral Integration Sites in the Cellular Genome ............... 42 4.2 Side Effects in Clinical and Preclinical Gene Therapy Studies ................... 45 5. New Strategies for Vector Biosafety in Gene Therapy . . 47 References ........................... 49 4. Lentiviral Vectors 53 Janka Mátrai, Marinee K. L. Chuah and Thierry VandenDriessche 1. Basic Viral Biology .................... 53 2. Vector Design and Production .............. 56 2.1 Vector Development ................ 56 2.2 Vector Production .................. 58 Contents 3. Gene Transfer Concepts and Potential Applications ... 59 3.1 Target Cells and Diseases .............. 59 3.2 Pseudotyping .................... 59 3.3 Cell Type Specific Targeting ............ 60 3.4 Integration-Defective Lentiviral Vectors ...... 60 4. Immune Consequences .................. 62 5. Safety Issues ....................... 63 6. Conclusions and Perspectives ............... 64 References ........................... 64 5. Herpes Simplex Virus Vectors 69 William F. Goins, David M. Krisky, James B. Wechuck, Darren Wolfe, Justus B. Cohen and Joseph C. Glorioso 1. Introduction ........................ 69 2. HSV Biology in the Design of Replication Defective Vectors 74 3. HSV Vector Design Technology ............. 77 4. Gene Transfer/Therapy Applications ........... 79 5. Immunology ....................... 80 6. Safety and Regulatory Issues ............... 81 7. Summary ......................... 81 References ........................... 82 6. Adeno-Associated Viral (AAV) Vectors 87 Nicholas Muzyczka 1. Introduction ........................ 87 2. Biology of AAV ...................... 88 3. Vector Technology .................... 93 4. Vector Characteristics In Vivo ............... 96 5. Next Generation Vectors ................. 98 6. Conclusions and Outlook ................. 99 References ........................... 99 A Guide to Human Gene Therapy 7. Regulatory RNA in Gene Therapy 103 Alfred. S. Lewin 1. Introduction ........................ 103 2. Delivery of Therapeutic RNAs .............. 106 3. Ribozymes ........................ 109 4. RNAi for Gene Therapy ................. Ш 5. Gene Therapy Using miRNA ............... 114 6. Aptamers, Decoys and Bi-Functional RNAs ....... 115 7. Modification of Cis-Acting Regulatory RNA Sequences ......................116 8. Conclusions ........................119 References ...........................120 8. DNA Integrating Vectors (Transposon, Integrase) 123 Lauren E. Woodard and Michele P. Calos 1. Basic Vector Biology ...................123 1.1 Transposon Systems ................124 1.2 Integrase Systems ..................126 2. Vector Design and Production ..............128 2.1 Design of Transposon Systems ........... 128 2.2 Design of Integrase Systems ............ 128 2.3 Production of Plasmid DNA............ 129 3. Gene Transfer Protocols and Potential Applications . . . 130 3.1 Hepatocy te Transfection via Hydrodynamic Injection .......................130 3.2 Lipophilic Complexes to Transfect Endothelial Cells and Glioblastoma ...............131 3.3 Direct DNA Injection and Electroporation to Target Muscle, Retina, and Joints ........131 3.4 Integration into Cultured Cells for Ex vivo Gene Therapy ...............131 4. Immunology .......................132 Contents 5. Safety and Regulatory Issues ............... 133 5.1 Integration Profiles and Associated Hazards .... 133 5.2 Efforts to Enhance Integration Specificity ..... 133 5.3 Effects on Tumor Latency in Mouse Models ofCancer ...................... 134 References ...........................135 9. Homologous Recombination and Targeted Gene Modification for Gene Therapy 139 Matthew Portem 1. Introduction ........................139 2. Problems with Using Gene Targeting by Homologous Recombination ......................140 3. Homologous Recombination in Embryonic Stem Cells .........................141 4. Homologous Recombination using Adeno-Associated Virus .................144 5. Site-Specific Modification of the Genome using Double-Strand Breaks ..................144 6. Double-Strand Break Repair ...............144 7. Double-Strand Break Induced Homologous Recombination ......................146 8. Re-design of Homing Endonucleases to Recognize New Target Sites .....................146 9. Development of Zinc Finger Nucleases .........147 10. Using Zinc Finger Nucleases to Stimulate Gene Targeting ......................147 11. Using Zinc Finger Nucleases to Site-Specifically Modify Genes by Mutagenic Non-Homologous End-Joining ........................149 12. Strategies of Zinc Finger Nuclease Design ........151 13. Aspects of Zinc Finger Binding Sites and Structure of Zinc Finger Nucleases .................153 14. Zinc Finger Nuclease Toxicity: Measuring and Minimizing ......................154 XIII A Guide to Human Gene Therapy 15. The Challenge of Delivery ................ 156 16. Future Directions and Promise of Homologous Recombination as a Gene Correction Approach to Gene Therapy ..................... 157 References ........................... 157 10. Gene Switches for Pre-Clinical Studies in Gene Therapy 163 Caroline Le Guiner, Knut Stieger, Alice Toromanoff, Fabienne Rolling, Philippe Moullier and Oumeya Adjali 1. Introduction ........................ 163 2. Rapamycin-Dependent Regulatable System....... 165 2.1 Molecular Mechanisms Involved in Transgene Regulation ..................... 165 2.2 Pharmacology of Rapamycin ............ 166 2.3 Translation Development of the Rapamycin Dependent Regulation System ........... 166 3. Tetracycline-Dependent Regulatable Systems ...... 168 3.1 Molecular Mechanisms Involved in Transgene Regulation ..................... 168 3.2 Pharmacology of Doxycycline (Dox) ........ 171 3.3 Translational Development of Tet-dependant Regulation Systems ................. 171 4. Other Regulatable Systems ................ 175 5. General Conclusions ................... 177 References ........................... 177 11. Gene Therapy for Central Nervous System Disorders 181 Deborah Young and Patricia A. Lawlor 1. Introduction ........................ 181 2. Gene Therapy for Parkinson s Disease .......... 182 3. Gene Therapy for Temporal Lobe Epilepsy ....... 186 4. Huntington s Disease Gene Therapy ........... 187 5. Amyotrophic Lateral Sclerosis (ALS).......... 189 6. Gene Therapy for Canavan Disease ............ 190 XIV Contents 7. Gene Therapy for Alzheimer s Disease .......... 191 8. Conclusions and Outlook ................. 193 References ........................... 194 12. Gene Therapy of Hemoglobinopathies 197 Angela E. Rivers andArun Srivastava 1. Introduction ........................ 198 2. ß-Thalassemia ...................... 198 3. Sickle Cell Disease .................... 199 4. Gene Therapy ....................... 200 4.1 Oncoretroviral Vector-Mediated Globin Gene Transfer .................... 202 4.2 Lentiviral Vector-Mediated Globin Gene Transfer .................... 203 4.3 Adeno-Associated Viral Vector-Mediated Globin Gene Transfer .................... 204 References ........................... 208 13. Gene Therapy for Primary Immunodeficiencies 213 Aisha Sauer, Barbara Cassami and Alessandro Aiuti 1. Introduction ........................ 214 2. Adenosine Deaminase (ADA)-deficient SCID ...... 215 3. X-Iinked Severe Combined Immunodeficiency (SCID-X1) ........................ 218 4. Gene Therapy for Other SCIDs .............. 220 4.1 V(D)J Recombination Defects ........... 220 4.2 Purine Nucleoside Phosphorylase (PNP) Deficiency ...................... 222 4.3 Janus Kinase 3 (ЈакЗ) Deficiency .......... 222 4.4 IL-7R Deficiency .................. 223 4.5 Zeta Associated 70 kDa Phosphoprotein (ZAP-70) Deficiency ................ 223 5. Wiskott-Aldrich-Syndrome (WAS) ............ 224 6. Chronic Granulomatous Disease ............. 225 7. Conclusions and Outlook ................. 227 References ........................... 228 XV A Guide to Human Gene Therapy 14. Gene Therapy for Hemophilia 233 David Markusic, Babak Moghimi and Roland Herzog 1. Introduction ........................ 233 2. Limitations of Hemophilia Treatment With Coagulation Factor Concentrates or Recombinant Coagulation Factors .................... 235 3. Gene Transfer for Correction of Hemophilia ....... 236 3.1 Ex Vivo Gene Transfer of F. VIII and F.IX ..... 236 3.2 In Vivo Gene Transfer of F.VIII and F.IX ...... 237 4. AAV is a Preferred Gene Therapy Vector for In Vivo Gene Transfer to Correct of Hemophilia ......... 238 5. Immunological Considerations for Efficient F.IX Gene Transfer ....................... 239 6. Advancements from Small and Large Animal Models of Hemophilia ....................... 242 6.1 Murine Hemophilia Models ............ 242 6.2 Canine Hemophilia Models ............. 242 7. Gene Therapy Trials for Hemophilia Past, Present, and Future ........................... 244 8. Conclusions ........................ 245 References ........................... 246 15. Gene Therapy for Obesity and Diabetes 251 Sergei Zolotukhin and Clive H. Wasserfall 1. Introduction ........................ 251 2. Understanding Obesity: Why We Get Fat ........ 252 2.1 Genetic Factors: Human Obesity Gene Map .... 252 2.2 Environmental Factors: The Big Two and Other Causal Contributors ................. 253 3. General Strategies in Gene Therapy for Obesity ..... 253 4. Gene Delivery Vehicles .................. 255 5. Gene Targets for Obesity ................. 255 5.1 Leptin ........................ 255 5.2 Neurocytokines ................... 256 xvi Contents 5.3 AMP-Activated Protein Kinase (AMPK)...... 256 5.4 Adiponectin..................... 257 5.5 Wnt-lOb....................... 257 5.6 Obesity Gene Menu à la Carte ........... 258 5.7 Obesity and Diabetes ................ 259 References ........................... 260 16. Gene Therapy for Duchenne Muscular Dystrophy 261 Takashi Okada and Shin ichi Takeda 1. Introduction ........................ 261 1.1 Background of Duchenne Muscular Dystrophy . . 261 2. Gene-replacement Strategies using Virus Vectors .... 262 2.1 Choice of Vector .................. 262 2.2 Modification of the Dystrophin Gene and Promoter .................... 264 2.3 Use of Surrogate Genes ............... 266 3. AAV-Mediated Transduction of Animal Models ..... 266 3.1 Vector Production .................. 266 3.2 Animal Models for the Gene Transduction Study ................. 267 3.3 Immunological Issues of rAAV ........... 268 3.4 Intravascular Vector Administration by Limb Perfusion ................. 269 3.5 Global Muscle Therapies .............. 269 4. Safety and Potential Impact of Clinical Trials ...... 270 5. Development of Alternative Strategies .......... 271 5.1 Design of Read-through Drugs ........... 271 5.2 Modification of rnRNA Splicing .......... 272 5.3 Ex Vivo Gene Therapy ............... 272 6. Future Perspectives .................... 273 6.1 Pharmacological Intervention ............ 273 6.2 Capsid Modification ................ 273 7. Conclusions and Outlook ................. 273 References ........................... 274 A Guide to Human Gene Therapy 17. Cancer Gene Therapy 279 Kirsten A.K. Weigel-Van Aken 1. Introduction ........................ 280 2. Targeting the Tumor Cell ................. 280 2.1 DNA Electroporation ................ 280 2.2 Non-Oncolytic Viral Vectors ............ 281 2.2.1 Retrovirus .................. 281 2.2.2 Lentiviras .................. 282 2.3 Oncolytic Viruses .................. 282 2.3.1 Herpesvirus ................. 283 2.3.2 Adenoviras .................. 283 2.3.3 Poxvirus ................... 284 2.3.4 Measles virus ................ 285 2.3.5 Vesicular stomatitis virus .......... 285 3. Targeting the Immune System .............. 286 3.1 Cancer Vaccines ................... 287 3.1.1 Vaccinia virus ................ 287 3.1.2 Lentivirus .................. 287 3.1.3 Adenoviras .................. 288 3.1.4 Parvovirases ................. 288 3.2 Mesenchymal Stem Cells (MSC) as Delivery Vehicles ................ 288 3.3 Adoptive Τ Cell Transfer .............. 288 4. Targeting the Tumor Microenvironment......... 289 5. Challenges and Risks of Cancer Gene Therapy ..... 289 6. Novel Strategies ...................... 290 6.1 Prime/Boost Regimens ............... 290 6.2 Immune Cells as Carriers for Virases ........ 290 7. Conclusions ........................ 291 References ........................... 291 18. Gene Therapy for Autoimmune Disorders 295 Daniel F. Gaddy, Melanie A. Rujjher and Paul D. Robbins 1. Introduction ........................ 295 2. Rheumatoid Arthritis ................... 296 Contents 2.1 Background ..................... 296 2.2 Existing Therapies ................. 296 2.3 Target Tissues and Routes of Delivery ....... 297 2.3.1 Local RA Gene Therapy ........... 297 2.3.2 Systemic RA Gene Therapy ......... 297 2.4 Immunomodulation................. 298 2.5 Overview of Preclinical Gene Therapy Studies . . 299 2.6 Overview of Clinical Gene Therapy Studies .... 301 3. Type I Diabetes Mellitus ................. 301 3.1 Background ..................... 301 3.2 Existing Therapies ................. 302 3.3 Target Tissues and Routes of Delivery ....... 303 3.4 Immunomodulation................. 303 3.5 Overview of Preclinical Gene Therapy Studies . . 305 3.6 Overview of Clinical Gene Therapy Studies .... 306 4. Conclusions and Outlook ................. 307 References ........................... 308 19. Gene Therapy for Inherited Metabolic Storage Diseases 311 Cathryn Mah 1. Introduction ........................ 311 2. Lysosomal Storage Diseases ............... 312 3. Glycogen Storage Diseases ................ 314 4. Animal Models ...................... 315 5. Cross-Correction Strategies ................ 319 6. Direct Correction of Target Tissues ............ 321 7. Conclusions and Outlook ................. 324 References ........................... 324 20. Retinal Diseases 327 Shannon E. Boye, Sanford L. Boye and William W. Hauswirth 1. Introduction ........................ 327 2. Rod and Cone Photoreceptors .............. 330 3. Cone Photoreceptors ................... 333 4. Retinal Ganglion Cells .................. 335 A Guide to Human Gene Therapy 5. Retinal Pigment Epithelium ............... 337 6. LCA2 Gene Therapy, a Perspective on Translational Research ......................... 339 References ........................... 342 21. A Brief Guide to Gene Therapy Treatments for Pulmonary Diseases 345 Ashley T. Martino, Christian Mueller and Terence R. Flotte 1. Introduction ........................ 345 2. Common Disorders .................... 346 2.1 Cystic Fibrosis ................... 346 2.2 Alpha- 1 Antitrypsin (Al AT) ............ 348 3. Development of Viral Vectors for Lung Disease ..... 348 3.1 Adenoviral Vectors ................. 349 3.2 Adeno-Associated Viral Vectors .......... 349 3.3 Early Conclusions ................. 349 4. Enhancing Efficiency ................... 350 4.1 Alternative AAV Viral Vector Serotypes ...... 350 4.1.1 Addition of Expression Enhancing Elements ................... 351 4.2 Adenoviral Vectors ................. 351 4.3 Physiological Hurdles in the Lung Environment .................... 352 5. Non-Viral Vectors ..................... 352 5.1 Cationic Liposomes ................. 352 5.2 Compacted DNA Nanoparticles .......... 353 6. Gene Therapy Development for Alpha- 1 Anti-trypsin ........................ 353 7. Lung Cancer Gene Therapy Development ........ 354 8. Cystic Fibrosis Animal Models .............. 355 9. Cell-Based Therapy for Cystic Fibrosis ......... 356 10. Conclusion and Outlooks ................. 357 References ........................... 358 Contents 22. Cardiovascular Disease 361 Darin J. Falk, Cathryn S. Mah and Barry J. Byrne 1. Introduction ........................ 361 2. Therapeutic Targets.................... 362 2.1 Congenital Heart Disease .............. 362 2.2 Coronary Artery Disease and Ischemia/ Reperfusion Injury ................. 365 2.3 Oxidative Stress ................... 365 2.4 Antioxidants .................... 366 2.5 Cardiac Contractility ................ 367 3. Animal Models ...................... 367 4. Vector Delivery ...................... 368 5. Conclusions and Outlook ................. 374 Acknowledgments ....................... 374 References ........................... 374 Index 379 XXI Ever since the birth of molecular biology, the tantalizing possibility of treating disease at its genetic roots has become increasingly feasible. Gene therapy— though still in its infancy — remains one of the hottest areas of research in medicine. Its approach utilizes a gene transfer vehicle ( vector ) to deliver therapeutic DNA or RNA to cells of the body in order to rectify the defect that is causing the disease. Successful therapies have been reported in humans in recent years such as cures in boys with severe immune deficiencies. Moreover, gene therapy strategies are being adapted in numerous biomedical laboratories to obtain novel treatments for a variety of diseases and to study basic biological aspects of disease. Correction of disease in animal studies, is steadily gaining ground, highlighting the immense potential of gene therapy in the medical profession. This book will cover topics that are at the forefront of biomedical research such as RNA interference, viral and non-virat gene transfer systems, treatment of hematologica! diseases and disorders of the central nervous system:. Leading experts on the respective vector or disease will contribute the individuai chapters and explain cutting-edge technologies, It also gives a broad overview of the most important gene transfer vectors and most extensively/ studied target diseases. This comprehensive guide is therefore a must-read for anyone in the biotechnology, biomedicai or medica! industries seeking to further their knowledge in the area of human gene therapy.
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spellingShingle	A guide to human gene therapy Gene therapy Gentherapie (DE-588)4296957-8 gnd
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title	A guide to human gene therapy
title_alt	Human gene therapy
title_auth	A guide to human gene therapy
title_exact_search	A guide to human gene therapy
title_full	A guide to human gene therapy ed.: Roland W. Herzog ...
title_fullStr	A guide to human gene therapy ed.: Roland W. Herzog ...
title_full_unstemmed	A guide to human gene therapy ed.: Roland W. Herzog ...
title_short	A guide to human gene therapy
title_sort	a guide to human gene therapy
topic	Gene therapy Gentherapie (DE-588)4296957-8 gnd
topic_facet	Gene therapy Gentherapie
url	http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=018985564&sequence=000003&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=018985564&sequence=000004&line_number=0002&func_code=DB_RECORDS&service_type=MEDIA
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