Concepts in gene therapy:
Gespeichert in:
| Format: | Buch |
|---|---|
| Sprache: | German |
| Veröffentlicht: |
Berlin [u.a.]
<<de>> Gruyter
1997
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| Schlagworte: | |
| Online-Zugang: | Inhaltsverzeichnis |
| Beschreibung: | XX, 553 S. Ill., graph. Darst. |
| ISBN: | 3110149842 |
Internformat
MARC
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| 245 | 1 | 0 | |a Concepts in gene therapy |c ed. Michael Strauss ... |
| 264 | 1 | |a Berlin [u.a.] |b <<de>> Gruyter |c 1997 | |
| 300 | |a XX, 553 S. |b Ill., graph. Darst. | ||
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| 650 | 4 | |a Gene Therapy | |
| 650 | 4 | |a Gene Transfer Techniques | |
| 650 | 4 | |a Gene therapy | |
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Datensatz im Suchindex
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| adam_text | Contents
I Methods of Gene Delivery
1. Retroviral Vectors 3
Brian Salmons and Walter H. Giinzburg
1.1 Introduction 3
1.2 General Retroviral Structure and Replication 4
( 1.3 Retroviral Vector Development 8
1.4 Use of Retroviral Vectors for Gene Therapy 17
1.5 Retroviral Vectors in Perspective 19
1.6 Conclusions 20
References 20
2. Adenoviral Vectors 25
r Patrice Yeh, Jean Francois Dedieu, Emmanuelle Vigne, Cecile Orsini and Michel
Perricaudet
2.1 Adenoviruses 25
2.2 Biology of the Virus 26
2.3 El deleted Vectors 28
2.4 Intrinsic Properties of El deleted Vectors 30
2.4.1 Residual (Leaky) Expression of the Viral Genome in vitro 30
2.4.2 In vivo Behaviour 32
2.5 Doubly defective Vectors 34
2.5.1 Rationale 34
2.5.2 The E2 Approach 34
2.5.3 The E4 Approach 35
2.6 From Gene Transfer to Therapy 36
References 38
3. Herpes Simplex Virus Mediated Gene Transfer to Neurons 43
W. F. Goins, T. Oligino, D. Krisky, P. Marconi, P. L. Poliani, R. Ramakrishnan,
D. J. Fink, and J. C. Glorioso
3.1 Introduction 43
3.2 HSV Genome and the Virus Life Cycle 44
X Contents
3.3 HSV Vector Cytotoxicity 45
3.4 Latent Infection and the Latency Promoter System 49
3.5 Quantitative Studies of the Establishment of HSV Latency in PNS
and CNS 51
3.6 Development of Transactivation Systems to Regulate Gene
Expression 53
3.6.1 Constitutive Activation of Transgene Expression Using the
GAL4:VP16 Transactivation System 53
3.6.2 Drug Inducible Transgene Activation from the Viral Genome 54
3.7 Summary 54
References 56
4. Adeno Associated Viral Vectors 61
D. M. McCarty and R. J. Samulski
4.1 Introduction 61
4.2 Recombinant AAV Vectors 61
4.3 Barriers to rAAV Transduction 63
4.4 Transduction of Non Dividing Cells 66
4.5 Episomal Expression 67
4.6 Adeno Associated Virus Integration 68
4.7 Recombinant AAV Vector Integration 69
4.8 Mechanism of AAV Integration 70
4.9 Transduction in vivo 71
4.10 Enhancement of rAAV Transduction in vivo 73
4.11 Conclusions 75
References 75
5. Virus Functions for Artificial Vectors 79
Volker Sandig and Michael Strauss
5.1 Introduction 79
5.2 Currently Used Viral Vectors 80
5.2.1 Retroviruses 80
5.2.2 Adenoviruses 80
5.2.3 Adeno Associated Virus 81
5.2.4 Herpes Viruses 81
5.3 Viral Mechanisms for Cellular Attachment 82
5.4 Viral Entry into the Cell 83
5.5 Transport to the Nucleus 85
5.6 Stability of Transferred Genes 88
5.6.1 Integration into the Host Genome 88
5.6.2 Extrachromosomal Persistence without Replication 89
5.6.3 Extrachromosomal Replication 90
Contents XI
5.7 Conclusion 92
References 92
6. Targeted Gene Delivery and Expression in Hepatocytes 99
George Y. Wu and Catherine H. Wu
6.1 A DNA Carrier System Targetable to Hepatocytes 99
6.2 Targeted Gene Delivery in Vitro 99
6.3 Targeted Gene Delivery in Vivo 100
6.4 Transient Gene Expression in an Animal Model of an Inherited
Metabolic Disorders 100
6.5 Prolongation of Targeted Gene Expression 101
6.6 The Mechanism of Persistence of Targeted Gene Expression
Achieved by Partial Hepatectomy 102
6.7 Incorporation of Endosomolytic Agents 103
6.8 Targeted Delivery of Antisense DNA 105
6.9 Conclusions 105
References 106
7. Particle Mediated Gene Delivery System for Cancer Research .... 109
Alexander L. Rakhmilevich and Ning Sun Yang
7.1 Introduction 109
7.2 Cancer Immunotherapy: Complex Problems and New Strategies .. 109
7.3 Current Techniques for in vivo Gene Transfer Ill
7.3.1 Virus mediated Gene Transfer Ill
7.3.2 Direct Gene Transfer 112
7.4 Particle Mediated Gene Transfer: Techniques and Potential
Application to Gene Therapy 112
7.4.1 Simultaneous Delivery of Multiple Therapeutic Genes 113
7.4.2 High Level Expression of Candidate Therapeutic Genes by Local
Delivery 114
7.4.3 In vivo Promoter Usage, Long Term Transgene Expression 115
7.5 Antitumor Effects of Gene Gun Mediated Cytokine Gene Transfer
in vivo: Transgenic Cytokine Secreted from Normal Skin Cells
Results in Tumor Regression 115
7.6 Gene Gun Mediated ex vivo Gene Transfer to Clinically Relevant
Tissue Samples 116
References H7
XII Contents
II Methods for Inactivation or Restoration of Gene Function
8. Gene Inactivation by Homologous Recombination Animal
Models of Plasma Lipoprotein Disorders 123
Thomas E. Willnow and Joachim Herz
8.1 Introduction 123
8.2 Methods for Gene Targeting in the Mouse 124
8.2.1 Gene Disruption by Homologous Recombination 124
8.2.2 Generation of Mice from Genetically Modified Embryonic Stem
Cells 125
8.2.3 Conditional Gene Disruption by Site Specific Recombination 127
8.3 Animal Models of Plasma Lipoprotein Disorders 130
8.3.1 Physiology and Pathophysiology of Lipoprotein Metabolism 130
8.3.2 The LDL Receptor Deficient Mouse 131
8.3.3 The apoE deficient Mouse 134
8.4 Conclusions 136
References 136
9. Potential Antisense Oligonucleotide Therapies for
Neurodegenerative Diseases 141
Mirta Grifman, Efrat Lev Lehman, Dalia Ginzberg, Fritz Eckstein, Haim Zakut and
Hermona Soreq
9.1 Introduction 141
9.2 The Concept of Phosphorothioate Modifications 143
9.3 False Positive and False Negative Outcome of AS ODNs 145
9.4 Drug Delivery 146
9.5 Antisense Modulation of Behavioral Phenotypes in Mammals .... 147
9.6 AS ODNs and Human Neuropathology 149
9.7 The Challenges of Alzheimer s disease 151
9.8 Human Cholinesterase Genes as Potential Targets for Antisense
Therapy 153
9.9 Effects of Antisense Oligonucleotides Targeted to Primary Neuron
mRNAs 154
9.10 In vitro and in vivo Tests for Potential Side Effects 158
9.11 Comparative Studies with AS ODNs for Genes with Closely
Related Functions 160
9.12 Discussion 162
References 164
10. Synthetic Ribozymes: The Hammerhead Ribozyme 169
Olaf Heidenreich and Fritz Eckstein
10.1 Introduction 169
Contents XIII
10.2 Structure and Function of the Hammerhead Ribozyme 169
10.3 The Synthesis of Ribozymes 172
10.4 What is the Optimal Length of a Ribozyme? 173
10.5 The Influence of RNA Secondary Structure on Ribozyme Catalysis 176
10.6 The Influence of RNA binding Proteins on Ribozyme Catalysis... 179
10.7 Colocalisation of Ribozymes and Target RNAs in the Cell 180
10.8 Chemically Modified Hammerhead Ribozymes 181
10.9 The Exogenous Delivery of Ribozymes 184
10.10 Potential Artefacts of Ribozyme Applications 185
10.11 Applications of Ribozymes in Cell Culture and Animal Models... 186
10.12 Perspectives 190
References 191
11. Ribozymes as Tools for the Gene Therapist 197
Lynn Milich and Bruce A. Sullenger
11.1 Introduction 197
11.2 Biochemistry of Catalytic RNAs 198
11.2.1 The Group I Intron from Tetrahymena 198
11.2.1.1 The Self Splicing Tetrahymena Intron 199
11.2.1.2 The Trans Cleaving Tetrahymena Ribozyme 199
11.2.1.3 The Trans Splicing Tetrahymena Ribozyme 203
11.2.2 The Hammerhead Ribozyme 204
11.2.3 The Hairpin Ribozyme 205
11.2.4 The Hepatitis Delta Virus (HDV) Ribozyme 206
11.2.5 The RNase P Ribozyme 206
11.2.6 Kinetic Analysis: A Pathway to Improve Ribozyme Catalysis 207
11.3 Therapeutic Applications: Trans Cleaving and Trans Splicing
Ribozymes 210
11.3.1 Trans Cleaving Ribozymes 210
11.3.1.1 Ribozyme Mediated Cleavage of HIV 1 RNA 210
11.3.1.2 Ribozymes and Cancer 213
11.3.1.3 Engineering Ribozymes 214
11.3.2 The Trans splicing Ribozyme from Tetrahymena thermophilia 218
11.4 Conclusions 220
References 221
III Cellular Target Systems
12. Gene Transfer and Transgene Expression in Hematopoietic Cells . 233
Christopher Baum, Carol Stocking, Thomas Wagener, Hans Georg Eckert and
Wolfram Ostertag
12.1 Introduction 233
XIV Contents
12.2 The Hematopoietic System 235
12.3 Sources and Enrichment of Target Cells 238
12.4 Transduction Systems 239
12.5 Selection and Expansion of Transduced Cells 242
12.6 Transgene Expression 247
12.7 Transgene Silencing 252
12.8 Conclusions 255
References 256
13. The Liver as a Target for Gene Therapy 267
Gunter Cichon and Michael Strauss
13.1 Introduction 267
13.2 Target Diseases 267
13.3 The Ideal Liver Vector 268
13.4 Gene Transfer Systems 269
13.4.1 Retroviruses 269
13.4.2 Adenoviral Vectors 270
13.4.3 Adeno Associated and Herpes Virus Based Vectors 272
13.4.4 Receptor Targeting by Polylysin DNA Complexes and Liposomes 273
13.4.5 Other Hybrid Systems 274
13.4.6 Liver Specific Gene Expression and Extrachromosomal
Stabilization of Therapeutic Genes 274
13.5 Immunological Aspects of Gene Transfer 275
13.6 Single Cell Transplantation and Recolonisation Strategies 276
13.7 Summary and Outlook 277
References 278
14. Gene Therapy for Gaucher Disease via Genetically Engineered
Primary Myoblasts 283
Chunming Liu, Simon Watkins, Alfred Bahnson and John A. Barranger
References 293
15. In vivo Secretion of Therapeutic Proteins from Neo Organs 297
Delphine Bohl and Jean Michel Heard
15.1 Conception and Realisation of Neo Organs 298
15.1.1 From Skin Equivalents to Neo Organs 298
15.1.2 Realisation and Characteristics of Neo Organs 300
15.1.3 Gene Transfer Procedures and Vehicles 302
15.2 Secretion of Therapeutic Proteins from Neo Organs 303
15.2.1 Secretion of Lysosomal Enzymes for the Treatment of
Mucopolysaccharidosis (MPS) 303
Contents XV
15.2.2 Secretion of Erythropoietin (Epo) for the Treatment of
Epo Responsive Anemias 305
15.2.3 Perspectives for the Treatment of HIV Infection 306
15.2.4 Perspectives for the Treatment of Hemophilias 306
15.3 Immunological Response against Neo Organ Components and
Secreted Proteins 307
15.4 Conclusions 308
References 308
IV Genetic Diseases
16. Gene Therapy for Cystic Fibrosis Strategies, Problems and
Perspectives 315
Charles Coutelle
16.1 Reasons for Gene Therapy of Cystic Fibrosis 315
16.2 The CFTR Gene, its Protein Product and Function 316
16.3 Preclinical Approaches to CF Gene Therapy 317
16.3.1 Nonintegrative Vector Systems 317
16.3.2 Integrative Vectors Systems 319
16.4 The First Clinical Trials for CF 320
16.4.1 Safety, Ethical and Legal Considerations 321
16.4.2 Testing for Efficacy 322
16.4.3 Adenovirus Trials 323
16.4.4 Cationic Lipid/DNA Trials 326
16.5 Assessment of Present Gene Therapy Vector Systems for CF 327
16.5.1 Adenoviral Vectors 327
16.5.2 Cationic Lipid Mediated Gene Transfer 330
16.6 Other Aspects of Gene Therapy for CF 332
16.6.1 Pulmonary Delivery 333
16.6.2 Other Organ Systems 334
16.6.3 Fetal Gene Therapy for CF 334
16.7 Outlook 335
References 336
17. Gene Therapy for Dystrophin Deficiency 347
George Dickson
17.1 Background and Concepts 347
17.2 Transgenic Animal Studies 349
17.3 DNA Mediated Gene Transfer 350
17.4 Adenoviral Vector Systems 351
17.5 Retroviral Vector Systems 353
17.6 Future Perspectives 354
XVI Contents
References 355
18. Gene Therapy For Familial Hypercholesterolemia 359
Michael Gotthardt and Herbert Schuster
18.1 Introduction 359
18.2 Familial Hypercholesterolemia (FH) 360
18.2.1 Definition 360
18.2.2 Phenotype 360
18.2.2.1 Biochemistry 360
18.2.2.2 Genomic and Protein Structure 361
18.2.2.3 Regulation of Gene Expression 361
18.2.3 Genotype 361
18.2.4 Population Genetics 362
18.2.5 Diagnosis 362
18.2.5.1 Differential Diagnosis 362
18.2.5.2 Laboratory Diagnosis 363
18.2.6 Therapy 363
18.2.6.1 Pharmacology 364
18.2.6.2 Surgery and Direct Interventions 364
18.2.6.3 Gene Therapy 365
18.3 Animal Models 366
18.4 Clinical Protocol 367
18.4.1 Prospects 368
18.5 Gene Therapy 369
18.5.1 Ex Vivo Gene Therapy 369
18.5.2 In Vivo Gene Therapy 370
18.5.2.1 Gene Transfer 370
18.5.3 Supportive Measures 373
18.5.3.1 Induction of Cell Division 373
18.5.3.2 Induction of Tolerance 374
18.5.3.3 Prenatal Gene Transfer 376
18.5.3.4 Homologous Recombination 376
18.6 Clinical Protocol 377
18.7 Summary 379
References 380
19. Therapeutic Strategies for the Lysosomal Storage Disorders 387
John A. Barranger, Michael J. Vallor, Randall Learish, Alfred Bahnson, Maya
Nimgaonkar, Edward Ball, Jane Mannion Henderson, Trina Mohney, James
Dunigan, Margeret Beeler, Joseph Mierski, Jason Lancia, Amy Kemp, and Erin Rice
19.1 Introduction 387
19.2 Animal Models of Lysosomal Storage Disorders 388
Contents XVII
19.2.1 The Gaucher Mouse Interpretation of Pathology 389
19.3 Therapeutic Strategies 393
19.3.1 Enzyme Therapy for Gaucher Disease 393
19.3.2 Transgenic Production of Large Amounts of Glucocerebrosidase.. 394
19.4 Gene Transfer Studies 395
19.4.1 Gaucher Disease 395
19.4.1.1 Synopsis of Data from Mouse Bone Marrow Transplants 398
19.4.1.2 Transfer and Expression of the GC Gene to Human Peripheral
Blood Stem Cells (PBSC) 400
19.4.1.3 Transduction of Gaucher and Non Gaucher Bone Marrow CD34+
Cells 400
19.4.1.4 Clinical Protocol of Gene Transfer in Patients with Gaucher
Disease 402
19.5 Metachromatic Leukodystrophy 403
References 407
V Non Genetic and Infectious Diseases
20. Gene Therapy for Arthritis 417
Steven C. Ghivizzani, Richard Kang, Christopher H. Evans and Paul D. Robbins
20.1 Introduction 417
20.2 Strategies for Treatment of RA with Gene Therapy 418
20.2.1 Local vs. Systemic Gene Delivery 418
20.2.2 Proteins with Anti arthritic Potential 419
20.3 Gene Transfer to the Synovium 420
20.4 Gene Delivery Systems 421
20.5 Gene Therapy for Arthritis in the Rabbit Knee Joint 422
20.6 Clinical Protocol for Gene Therapy of Arthritis 424
20.7 Gene Transfer to Articular Chondrocytes 425
20.8 Animal Models of Arthritis Induced by Gene Transfer 426
References 427
21. Gene Therapy for HIV 1 Disease 431
Ernst Bohnlein
21.1 HIV 1: A New Challenge for Medical Research 431
21.2 Gene Therapy: An Alternative Approach 432
21.2.1 HIV 1 Gene Therapy: Clinical Issues 433
21.2.2 Genetic Immune Restoration 434
21.2.3 Intracellular Gene Therapy Approaches 435
21.2.3.1 Intracellular Immunization 435
21.2.3.2 Therapeutic Genes 437
21.2.3.3 Target Cells 444
XVIII Contents
21.2.3.4 Gene Delivery 447
21.2.3.5 Clinical Trials 449
21.3 Future Directions 449
References 453
VI Cancer
22. Suicide Genes for the Treatment of Cancer 469
Kenneth W. Culver
22.1 Introduction 469
22.2 Mechanisms of Suicide Gene Action 469
22.2.1 General Concepts 469
22.2.2 The Herpes Simplex Thymidine Kinase (HS tk) Gene 470
22.2.3 Cytosine Deaminase (CD) 471
22.2.4 Other Suicide Genes 472
22.3 Preclinical Studies with HS tk and CD 472
22.4 The Bystander Tumor Killing Effect 475
22.5 Clinical Applications 476
22.5.1 In Vivo Gene Transfer 476
22.5.1.1 Brain Tumors 476
22.5.1.2 Leptomeningeal Carcinomatosis 479
22.5.1.3 Mesothelioma 479
22.5.1.4 Ovarian Cancer 479
22.5.1.5 Liver Cancer 480
22.5.1.6 Head/Neck Cancer 480
22.5.1.7 Prostate Cancer 480
22.5.2 Ex Vivo Gene Transfer 480
22.5.2.1 Ovarian Cancer 480
22.5.2.2 T Lymphocyte Gene Therapy Protocols 481
22.6 Combination Therapy of HS tk and Cytokine Genes 481
22.7 Conclusions 482
References 482
23. Tumor Cell Vaccines Using Genetically Modified Cells
Coexpressing Cytokines and the T Cell Costimulatory Molecule B7 487
Sophie Cayeux, Bernd Dorken and Thomas Blankenstein
23.1 Introduction 487
23.2 Tumor Cell Vaccines Coexpressing Cytokine and B7.1 Genes .... 490
23.2.1 Construction of B7.1 Gene Expression Vectors and Retroviral
Gene Transfer Experiments 490
23.2.2 Cooperative Effect of B7.1 Expression and IL 7 or IL 4 Secretion
on Tumor Rejection 491
Contents XIX
23.2.3 Vaccination Efficiency of IL 7/B7.1 or IL 4/B7.1 Coexpressing
Cells is Superior to Single Gene Transfectants and to Adjuvant
C. parvum 491
23.2.4 Irradiation of Tumor Cells Prior to Immunization Abrogates the
Vaccine Effect 493
23.3 Mechanisms of Tumor Rejection Induced by Cytokine and/or B7.1
Modified Tumor Cell Vaccines 497
23.3.1 Cytokine but Not B7.1 Transfected Cells Suppress Tumor Growth
of Coinjected Parental Cells 498
23.3.2 Analysis of Cells Infiltrating Tumor Tissue 498
23.3.3 Growth of Tumor Cell Lines in Nude and SCID Mice 500
23.4 Conclusion 501
References 502
24. Dosage Impact on Immunotherapy with Cytokine Gene Modified
Cancer Vaccines 505
Walter Schmidt
24.1 Introduction 506
24.1.1 Adjuvants 506
24.1.2 Xenogenization upon Viral Infection 507
24.1.3 Transfection with Cytokine Genes 507
24.2 Reduced Tumorigenicity upon Cytokine Transgene Expression ... 508
24.3 Cancer Vaccines in Experimental Animal Models 509
24.3.1 Pioneering Studies 509
24.4 Vaccination with Viable Tumor Cells 509
24.4.1 IL 2 in Murine Mammary Carcinomas 510
24.4.2 Comparison with Adjuvants 511
24.5 Inactivated Cancer Vaccines 512
24.6 Cytokine Dosage as the Critical Parameter for Cancer Vaccination 513
24.7 Conclusion 516
References 516
25. Tumor Suppressor Gene Therapy Growth Arrest and
Programmed Cell Death 521
Michael Strauss, Karsten Brand and Volker Sandig
25.1 Introduction 521
25.2 Mechanisms of Cell Cycle Regulation 522
25.2.1 Oncogenes and Tumor Suppressors 522
25.2.2 Cell Cycle Regulation by Cyclins and Cyclin Dependent Kinases . 523
25.2.3 Inhibitors of Cyclin Dependent Kinases 523
25.2.4 Gl Phase Control and the Restriction Point 524
25.2.5 Deregulation of the Restriction Point in Most Tumors 524
XX Contents
25.3 Regulation of Apoptosis 526
25.4 Tumor Suppressor Gene Therapy 527
25.4.1 Rb Gene Transfer 527
25.4.2 p53 Gene Transfer 527
25.4.3 Kinase Inhibitor Gene Transfer 529
25.4.4 Combined Tumor Suppressor Gene Transfer 530
25.5 Future Developments 531
25.6 Outlook 532
References 533
Contributors 539
Index 547
|
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| discipline | Biologie Medizin |
| format | Book |
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| genre | (DE-588)4143413-4 Aufsatzsammlung gnd-content |
| genre_facet | Aufsatzsammlung |
| id | DE-604.BV011508100 |
| illustrated | Illustrated |
| indexdate | 2024-07-09T18:10:57Z |
| institution | BVB |
| isbn | 3110149842 |
| language | German |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-007744680 |
| oclc_num | 37481338 |
| open_access_boolean | |
| owner | DE-29 DE-29T DE-12 DE-20 DE-19 DE-BY-UBM DE-634 DE-578 |
| owner_facet | DE-29 DE-29T DE-12 DE-20 DE-19 DE-BY-UBM DE-634 DE-578 |
| physical | XX, 553 S. Ill., graph. Darst. |
| publishDate | 1997 |
| publishDateSearch | 1997 |
| publishDateSort | 1997 |
| publisher | <<de>> Gruyter |
| record_format | marc |
| spelling | Concepts in gene therapy ed. Michael Strauss ... Berlin [u.a.] <<de>> Gruyter 1997 XX, 553 S. Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier Gentherapie gtt Gene Therapy Gene Transfer Techniques Gene therapy Gentherapie (DE-588)4296957-8 gnd rswk-swf (DE-588)4143413-4 Aufsatzsammlung gnd-content Gentherapie (DE-588)4296957-8 s DE-604 Strauss, Michael Sonstige oth HBZ Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=007744680&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Concepts in gene therapy Gentherapie gtt Gene Therapy Gene Transfer Techniques Gene therapy Gentherapie (DE-588)4296957-8 gnd |
| subject_GND | (DE-588)4296957-8 (DE-588)4143413-4 |
| title | Concepts in gene therapy |
| title_auth | Concepts in gene therapy |
| title_exact_search | Concepts in gene therapy |
| title_full | Concepts in gene therapy ed. Michael Strauss ... |
| title_fullStr | Concepts in gene therapy ed. Michael Strauss ... |
| title_full_unstemmed | Concepts in gene therapy ed. Michael Strauss ... |
| title_short | Concepts in gene therapy |
| title_sort | concepts in gene therapy |
| topic | Gentherapie gtt Gene Therapy Gene Transfer Techniques Gene therapy Gentherapie (DE-588)4296957-8 gnd |
| topic_facet | Gentherapie Gene Therapy Gene Transfer Techniques Gene therapy Aufsatzsammlung |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=007744680&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
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