Adenoviral vectors for gene therapy:
Gespeichert in:
| Weitere Verfasser: | |
|---|---|
| Format: | Buch |
| Sprache: | English |
| Veröffentlicht: |
Amsterdam [u.a.]
Acad. Press
2002
|
| Schlagworte: | |
| Online-Zugang: | Inhaltsverzeichnis |
| Beschreibung: | Includes bibliographical references |
| Beschreibung: | XXVIII, 677 S. Ill., graph. Darst. |
| ISBN: | 0121995046 |
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| 245 | 1 | 0 | |a Adenoviral vectors for gene therapy |c ed. by David T. Curiel ... |
| 264 | 1 | |a Amsterdam [u.a.] |b Acad. Press |c 2002 | |
| 300 | |a XXVIII, 677 S. |b Ill., graph. Darst. | ||
| 336 | |b txt |2 rdacontent | ||
| 337 | |b n |2 rdamedia | ||
| 338 | |b nc |2 rdacarrier | ||
| 500 | |a Includes bibliographical references | ||
| 650 | 7 | |a Adenoviridae |2 ram | |
| 650 | 7 | |a Adenovírus |2 larpcal | |
| 650 | 4 | |a Adénovirus | |
| 650 | 7 | |a Genes virais |2 larpcal | |
| 650 | 4 | |a Thérapie génique | |
| 650 | 2 | |a Thérapie génique | |
| 650 | 7 | |a Thérapie génique |2 ram | |
| 650 | 7 | |a Vecteurs de clonage |2 ram | |
| 650 | 7 | |a Vírus de dna |2 larpcal | |
| 650 | 4 | |a Adenoviridae | |
| 650 | 4 | |a Adenoviruses | |
| 650 | 4 | |a Gene Therapy |x methods | |
| 650 | 4 | |a Gene therapy | |
| 650 | 4 | |a Genetic Vectors |x therapeutic use | |
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| 650 | 0 | 7 | |a Adenoviren |0 (DE-588)4141412-3 |2 gnd |9 rswk-swf |
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Datensatz im Suchindex
| _version_ | 1804129326267891712 |
|---|---|
| adam_text | Contents
Contributors xxiii
Preface xxvii
CHAPTER 1
Adenovirus Structure
Phoebe L. Stewart
I. Introduction 1
II. Molecular Composition 2
III. Structure of the Intact Virion 3
IV. Structure of the Capsid Components 4
A. Hexon, Polypeptide II 4
B. Penton Base, Polypeptide III 6
C. Fiber, Polypeptide IV 8
D. Polypeptide Ilia 10
E. Polypeptide VI 10
F. Polypeptide VIII 11
G. Polypeptide IX 11
v
vi Contents
V. Core Structure 12
VI. Adenovirus Protease 12
VII. Summary 13
References 14
CHAPTER 2
Biology of Adenovirus Cell Entry
Glen R. Nemerow
I. Pathway of Adenovirus Cell Entry 19
II. Cell Receptors Involved in Attachment 21
A. CAR 21
B. Other Adenovirus Receptors 23
III. Adenovirus Internalization Receptors 24
A. Role of av Integrins as Coreceptors 24
B. Structural Features of Penton Base av Integrin
Association 26
C. Signaling Events Associated with Adenovirus
Internalization 26
IV. Virus Mediated Endosome Disruption and Uncoating 29
A. Role of Penton Base and av Integrins 29
B. Role of the Adenovirus Cysteine Protease 30
V. Beyond the Endosome: Trafficking of Viral Capsids and Import of
Viral DNA into the Nucleus 30
A. Intracytoplasmic Transport of Viral Capsids 30
B. Docking at the Nuclear Pore and Translocation of Viral
DNA 31
VI. Conclusions 31
References 32
CHAPTER 3
Adenovirus Replication
Jared D. Evans and Patrick Hearing
I. Introduction 39
II. Classification 40
Contents vjj
III. Genome Organization 40
IV. Virus Infection 42
V. Early Gene Expression 42
VI. Early Region 1A(E1A) 43
VII. Early Region 1B(E1B) 46
VIII. Early Region 2 (E2) 47
IX. Early Region 3 (E3) 49
X. Early Region 4 (E4) 52
XI. Viral DNA Replication 55
XII. VA RNA Genes 59
XIII. Late Gene Expression and Virus Assembly 59
XIV. Vector Design 62
XV. Conclusion 63
References 64
CHAPTER 4
Adenoviral Vector Construction I: Mammalian Systems
Philip Ng and Frank L. Graham
I. Introduction 71
A. Adenovirus Biology 71
B. Adenovirus Vectors 73
C. Early Methods of Constructing Recombinant
Adenoviruses 73
II. The Two Plasmid Rescue System 75
A. Development of the Two Plasmid Rescue System 77
B. Refinements to the Two Plasmid Rescue Method 79
C. The Ad Genomic Plasmid 82
D. The Shuttle Plasmid 82
III. Protocols for the Two Plasmid Rescue System 85
A. Preparation of Plasmid DNA 85
B. Cell Culture 88
C. Cotransfection 89
D. Analysis of Recombinant Vectors and Preparation of Working
Vector Stocks 93
viii Contents
E. Titration of Adenovirus 94
F. Preparation of High Titer Viral Stocks (Crude
Lysate) 95
G. Purification of Adenovirus by CsCl Banding 97
H. Characterization of Adenoviral Vector
Preparations 99
I. Alternative Procedures to Expedite Vector
Production 101
References 101
CHAPTER 5
Adenoviral Vector Construction II: Bacterial Systems
M. Lusky, E. Degryse, M. Mehtali, and C. Chartier
I. Introduction 105
II. Generation of Ad: Traditional Approaches 106
III. Generation of Ad: Bacterial Systems 107
IV. Homologous Recombination in £. coli 108
V. Homologous Recombination with Linear Ad Vector Genome
Plasmids 109
VI. Homologous Recombination with Circular Ad Vector Genome
Plasmids 116
VII. Ad Vector Construction by Transposon Mediated
Recombination 118
VIII. Ad Vector Construction by in Vitro Ligation 119
IX. Conclusion 121
References 123
CHAPTER 6
Propagation of Adenoviral Vectors: Use ofPER.C6 Cells
W. W. Nichols, R. Lardenoije, B. J. Ledwith, K. Brouwer, S. Manam, R. Vogels,
D. Kaslow, D. Zuidgeest, A. J. Beft, L. Chen, M. van der Kaaden,
S. M. Galloway, R. B. Hill, S. V. Machotka, C. A. Anderson, J. Lewis,
D. Martinez, J. Lebron, C. Russo, D. Valerio, and A. Bout
I. Introduction 129
Contents jx
A. Scope of the Chapter 129
B. Adenoviruses 130
C. Adenovirus Replication 131
II. Cells Expressing El of Adenovirus 134
A. Transformation of Cells by El of
Adenovirus 134
B. El Expressing Cell Lines for Adenoviral Vector
Production 135
III. PER.C6 Prevents RCA during Vector Production 136
A. RCA 136
B. PER.C6: Absence of Sequence Overlap Eliminates RCA
Generation 137
C. Frequency of RCA Occurrence 139
IV. Production of Adenoviral Vectors 141
A. Vector Stability 141
B. The Production Process 143
C. Yields of Adenoviral Vectors 145
D. Scale of Adenoviral Vector Production 145
V. Safety Considerations of PER.C6 146
A. QC Testing of PER.C6 Cells for Use in the Manufacture of
Biologicals and Vaccines 146
B. Tumorigenicity 150
C. Prion Related Issues 156
D. Genetic Characterization of PER.C6 Cells 157
VI. Conclusions 159
References 160
CHAPTER 7
Purification of Adenovirus
Paul Shabram, Gary Vellekamp and Carl Scandella
I. Introduction 167
A. The Physical Characteristics of the Adenovirus Particle in
Solution 167
X Contents
B. Features of the Milieu 170
C. Summary of Characteristics 173
II. Recovery and Purification of Adenoviral Particles 173
A. Harvest Methods 173
B. Lysis Methods 175
C. Clarification 179
D. Purification 181
E. Buffer Exchange 189
III. Analytical Methods for Process Development and Process
Tracking 190
A. Plaque Forming Titer Assays 190
B. Adenovirus 96 Well Titer Plate Assay 191
C. Flow Cytometry 194
D. Particle Concentration Determination by Ultraviolet
Absorbance 194
E. Analytical Reverse Phase HPLC 195
F. Analytical Anion Exchange HPLC 196
IV. Formulation and Stability 196
V. Conclusions 200
References 200
CHAPTER 8
Targeted Adenoviral Vectors I: Transductional Targeting
Victor Krasnykh and Joanne T. Douglas
I. Introduction 205
II. The Pathway of Adenoviral Infection 206
III. Strategies and Considerations 207
IV. Conjugate Based Targeting 209
A. Bispecific Chemical Conjugates 209
B. Bispecific Recombinant Fusion Proteins 213
C. Bispecific Peptides 215
D. Polymer Mediated Coupling of Ligands to Ad Capsid
Proteins 215
Contents xj
E. Biotinylated Ad/Avidin Bridge/Biotinylated
Ligand 216
V. Genetic Targeting 216
A. Ad Targeting Strategies Involving Genetic Manipulations of
the Fiber Protein 217
B. Ad Targeting Strategies Involving Genetic Manipulations of
the Hexon and Penton Base Proteins 231
VI. Transductionally Targeted Ad Vectors for Clinical Gene Therapy
Applications 232
VII. Conclusion 235
References 236
CHAPTER 9
Targeted Adenoviral Vectors II: Transcriptional Targeting
Sudhanshu P. Raikwar, Chinghai H. Kao, and Thomas A. Gardner
I. Introduction: Rationale of Transcriptional Targeting 247
II. Regulation of Transcription in Eukaryotes 248
A. Molecular Organization of DNA 248
B. The Central Dogma 248
C. Transcription 249
D. Mechanism of Transcription 251
E. Structural Motifs 253
F. Regulation of Adenoviral DNA Transcription
Process 256
III. Approaches of Transcriptional Regulation 256
A. Prior Rationale Universal Promoters 256
B. Current Rationale of Tissue Specific Promoters 257
C. MN/CA9 Promoter 268
D. Inducible Transcription 269
IV. Enhanced Control of Transgene Expression 271
A. Safety Improvements 271
B. Potency Concerns 272
V. Future Directions 272
A. Enhancement of Weak But Specific Promoters 272
xii Contents
B. Improving Specificity with Multiple Promoter
Segments 274
C. Tumor Specific Oncolysis 274
D. Combined Targeting Approaches 274
VI. Summary 274
References 275
CHAPTER 10
Development of Attenuated Replication Competent
Adenoviruses (ARCAs) for the Treatment of Prostate Cancer
Daniel R. Henderson and De Chao Yu
I. Introduction 287
II. ARCAs for Prostate Cancer: CV706 and
CV787 290
A. Adenovirus: Gene Expression and
Regulation 290
B. Tissue Specificity of ARCA 291
C. Antitumoral Efficacy of ARCA 295
D. Mechanism for Cell Killing of ARCA 296
III. Synergy of ARCA and Conventional Therapy 298
A. Synergy of CV706 and Irradiation 299
B. Synergy of CV787 and Chemotherapy 302
IV. Toxicity of Intravenously Administered ARCAs in the Absence or
Presence of Docetaxel 305
V. Effects of Preexisting Adenovirus Antibody on Antitumor Activity and
Immunoapheresis for Human Therapy 308
A. Preexisting Adenovirus Antibodies Inhibit Systemic Toxicity
and Antitumor Activity 309
B. SIAPA: Screening and Immunoapheresis of Preexistent
Antibody for Monitoring and Removing Preexistent Ad5
Antibodies from Blood 313
VI. Clinical Development of CV706 and CV787 314
A. CV706 Phase I/II Trial for Locally Recurrent Prostate
Cancer 314
B. Factors Impacting Clinical Efficacy and Safety 317
Contents xiii
VII. Summary 318
References 319
CHAPTER 1 1
Replication Selective Oncolytic Adenovirus El Region Mutants:
Virotherapy for Cancer
David Kirn
I. Introduction 329
II. Attributes of Replication Selective Adenoviruses for Cancer
Treatment 332
III. Biology of Human Adenovirus 332
IV. Mechanisms of Adenovirus Mediated Cell Killing 333
V. Approaches to Optimizing Tumor Selective Adenovirus
Replication 333
VI. E1A CR2 Region Deletion Mutants 334
VII. El B 55 kDa Gene Deletion Mutant: d/1 520 335
VIII. Clinical Trial Results with Replication Competent Adenoviruses in
Cancer Patients 337
A. Clinical Trial Results with Wild Type Adenovirus 337
B. A Novel Staged Approach to Clinical Research with
Replication Selective Viruses: The Example of J/1520
(Onyx 015) 338
IX. Results from Clinical Trials with d/1520 (Onyx 015 or
Cl 1042) 340
A. Toxicity 340
B. Viral Replication 340
C. Immune Response 342
X. Clinical Trial Results with d/1520 (Onyx 015): Summary 343
XI. Future Directions: Why Has d/1520 (Onyx 015) Failed to Date as a
Single Agent? 344
XII. Improving the Efficacy of Replication Selective Oncolytic Adenoviral
Agents 345
XIII. Summary 345
References 346
xiv Contents
CHAPTER 12
Innate Immune Responses to in Vivo Adenovirus Infection
Bruce C. Trapnell and Thomas P. Shanley
I. Overview: Components of Innate Immunity 349
II. Distribution and Clearance of Adenovirus from the Respiratory
Tract 354
A. Clinical Aspects of Natural Adenoviral Infection in
Humans 354
B. Distribution of Recombinant, Replication Deficient
Adenoviral Vectors 355
C. Kinetics and Mechanisms of Clearance of
Adenovirus 356
III. Molecular Mediators of Inflammation 359
A. Clinical Adenovirus Infections in Humans 360
B. Adenovirus Infections in Animal Models 361
C. Acute Cytokine Responses 362
D. Intermediate Cytokine Responses 363
E. Late Cytokine Responses 364
IV. Inflammatory Cell Recruitment 364
V. Innate Immunity and Programming of Adaptive Responses 367
VI. Innate Immunity and in Vivo Gene Therapy 368
VII. Future Directions 369
References 369
CHAPTER 13
Humoral Immune Response
Catherine O Riordan
I. Introduction 375
II. Adenovirus Structure and Serotype 376
A. Classification of Adenoviruses 376
B. Adenoviral Structural Proteins and Type Specific
Epitopes 376
C. Chimeric Adenovirus Vectors 379
Contents XV
D. Influence of Serotypic Variations on Adenoviral Cell
Interactions 380
III. Host Response to Gene Therapy Vectors 381
A. Innate Immune Response 381
B. Adaptive Immune Response: B T Cell Interactions 382
IV. Strategies to Overcome the Humoral Immune Response 384
A. General Immunosuppression 384
B. Transient Selective Immunosuppression 386
C. Oral Tolerance 387
D. Serotype Switching 388
E. Masking Neutralizing Epitopes 389
F. Immunoapheresis 390
V. Factors Modulating Host Responses to Gene Transfer
Vectors 390
A. Viral Vector Backbone 390
B. Species and Strain 393
C. Route of Delivery 395
VI. Immune Response to Adenoviral based Vectors in
Humans 396
VII. Conclusion 398
References 399
CHAPTER 14
Novel Methods to Eliminate the Immune Response to
Adenovirus Gene Therapy
Huang Ge Zhang, Hui Chen Hsu, and John D. Mountz
I. Introduction 409
II. Immune Suppression 410
III. Immune Modulation 411
IV. Treatment with Soluble TNFR1 to Eliminate Ad Inflammation in Lung
and Liver 414
V. Inhibition of Cell Cytolysis Which Combines Treatment with Soluble
DR5, Soluble Fas, and Soluble TNFR1 415
VI. Immune Privilege 417
xvi Contents
VII. APC AdFasL Prolongs Transgene Expression and Specifically
Minimizes T Cell Response 419
VIII. Production of AdsTACI Prolongs Gene Expression and Minimizes
B Cell Response 421
IX. Summary 423
References 424
CHAPTER 15
High Capacity Gutless Adenoviral Vectors: Technical Aspects
and Applications
Gudrun Schiedner, Paula R. Clemens, Christoph Volpers, and Stefan Kochanek
I. Introduction 429
II. Technical Aspects 430
A. Vector Production 430
B. Sniffer DNA 432
C. Vector Capsid Modification 434
III. Applications 435
A. Liver Gene Transfer 435
B. Gene Transfer into Skeletal Muscle 439
C. Gene Transfer into the Eye and into the CNS 440
IV. Conclusion 442
References 442
CHAPTER 16
Xenogenic Adenoviral Vectors
Gerald W. Both
I. Impetus and Rationale 447
II. Classification of Adenoviruses 447
III. Factors Affecting Vector Design and Utility 448
A. Host Range and Pathogenicity 448
B. Neutralization 450
C. Genome Structure and Function 450
Contents xvii
D. Transforming Ability 454
E. Cell Lines 456
F. Strategies for Vector Construction and Rescue 458
IV. Utility of Xenogenic Vectors 460
A. Veterinary Studies 460
B. Vector Biology 462
C. Gene Therapy Studies 466
V. Biosafety 466
A. Complementation and Recombination 466
B. Oncogenes in Viral and Cellular DNA 468
C. Virus/Cell Interactions 468
D. Replication Competent Viruses 469
VI. Vector Production and Purification 469
References 470
CHAPTER 17
Hybrid Adenoviral Vectors
Stephen J. Murphy and Richard G. Vile
I. Introduction 481
A. Retroviral Vectors 483
B. Adenoviral Vectors 487
C. Adeno associated Viruses 487
D. Herpes Simplex Viruses 488
E. Lentiviral Vectors 488
F. The Choice of Gene Therapy Vector 489
G. How to Maintain Stable Transgene Expression 491
II. Hybrid Viral Vectors 492
A. Are Hybrid Vectors Truly New Technology? 493
III. Hybrid Adenoviral Vector Systems 494
A. Pseudotyping and Retargeting Adenoviral
Vectors 494
B. Adenoviral/Retroviral Hybrid Vector
Technologies 496
xviii Contents
C. Adenoviral/Epstein Barr Virus Hybrid Vectors 508
D. Hybrid Retro viruses Trafficking to the Nucleus 511
E. Hybrid Adenoviral/Adeno Associated Virus Vectors 512
IV. Conclusion 518
References 524
CHAPTER 18
Utility of Adenoviral Vectors in Animal Models of Human
Disease I: Cancer
Raj K. Batra, Sherven Sharma, and Lily Wu
I. Introduction 533
II. Animal Models of Lung Cancer 535
A. Human Lung Cancer 535
B. Animal Models of Human Lung Cancer 537
C. Gene Therapy of Lung Cancer Using Adenoviral
Vectors 543
III. Animal Models of Human Prostate Cancer 547
A. Human Prostate Cancer 547
B. Spontaneous and Transgenic Models of Human Prostate
Cancer 547
C. Xenograft Models of Human Prostate Cancer 548
D. Gene Therapy Approaches with Adenovectors in Prostate
Cancer 550
IV. Summary and Discussion 551
References 553
CHAPTER 19
Utility of Adenoviral Vectors in Animal Models of Human
Disease II: Genetic Disease
Raymond John Pickles
I. Introduction 565
II. Pathophysiology of Cystic Fibrosis (CF) Lung Disease 566
Contents xix
III. Trials and Tribulations with Adenoviral Vectors for CF Lung
Disease 567
IV. The Airway Epithelium: Cellular Targets for CF Gene
Therapy 568
V. Adenoviral Vectors as Gene Transfer Vectors in the Lung 570
A. Animal Models for CF Airway Gene Transfer
Studies 570
B. Success and Limitations of Ad 571
C. Overcoming the Limitations of Ad 577
VI. Other Vectors 585
VII. Conclusion 586
References 586
CHAPTER 2 0
Utility of Adenoviral Vectors in Animal Models of Human
Disease III: Acquired Diseases
Erik Lubberts and Jay K. Kolls
I. Adenoviral Vectors for Infectious Disease 595
A. Tuberculosis 596
B. Pneumonia 598
C. Opportunistic Infections 601
D. Viral Hepatitis 603
II. Chronic Inflammatory Diseases 603
A. Inflammatory Bowel Disease 603
B. Arthritis 604
C. Fibrotic Lung Disease 607
III. Conclusions 608
References 608
CHAPTER 2 1
Testing of Adenoviral Vector Gene Transfer Products:
FDA Expectations
Steven R. Bauer, Anne M. Pilaro, and Karen D. Weiss
I. Introduction 615
XX Contents
II. Manufacturing Control and Product Characterization 616
A. Purity, Safety, and Potency 616
B. Regulation of Process as Well as Product 617
C. Current Good Manufacturing Practices 617
III. Development of Recommendations for the Manufacture and
Characterization of Adenoviral Vectors 618
IV. Considerations in Manufacturing Adenoviral Vectors 620
A. Components and Characterization 620
B. Protocols 621
V. Process Controls 621
A. Standard Operating Procedures 621
B. Quality Assurance and Quality Control
Programs 622
VI. Characterization of Adenoviral Vector Production
Intermediates 623
A. Master Cell Bank 623
B. Working Cell Bank 626
C. Master Virus Bank 626
VII. Characterization of Adenoviral Vector Final
Products 628
VIII. Preclinical Testing of Adenoviral Vectors 630
A. Pharmacologic Activity 631
IX. Toxicology Testing 632
A. Scope of Toxicity Testing 632
B. Species Selection 633
C. Route of Administration 634
D. Selection of Dose 634
X. Biodistribution 636
A. Good Laboratory Practices 637
XI. Introduction to Clinical Testing 637
A. Phases of Clinical Development 638
XII. Good Clinical Practices 639
A. Responsibilities of a Sponsor and
Investigators 639
B. Adverse Event Reporting 639
Contents xxi
C. Consent and Vulnerable Populations 640
D. Monitoring and Auditing 641
XIII. Clinical Safety of Adenoviral Vector Products 642
XIV. Bioactivily of Adenoviral Vector Products 643
XV. Clinical Efficacy of Adenoviral Vector Products 644
A. Choice of Control 645
B. Endpoint Selection 645
XVI. How the Role of FDA Regulators Has Changed Since September
1999 646
A. Safety Symposia in Conjunction with OBA 647
B. Results of FDA s Directed Inspections 648
C. Description of the March 6, 2000, Letter and Summary of
Responses 649
D. Results of Additional Inspections 650
E. Sponsor Outreach and Education 651
XVI. Summary 651
References 652
CHAPTER 2 2
Imaging Adenovirus Mediated Gene Transfer
Kurt R. Zinn and Tandra R. Chaudhuri
I. Introduction 655
II. What Information Is Provided by Imaging? 656
III. Scientific Basis for Imaging 657
A. Electromagnetic Energy 657
B. Contrast 657
C. Gamma Rays and Detection 657
D. Light Based Imaging and Detection 661
E. Magnetic Resonance Imaging and
Spectroscopy 662
IV. Imaging and Gene Therapy Vectors 663
A. Gamma Ray Imaging 663
B. Light Based Imaging 666
C. Magnetic Resonance Technologies 668
xxii Contents
V. Gene Therapy Vectors May Advance Molecular
Imaging 669
VI. Conclusion 671
References 671
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| id | DE-604.BV014546631 |
| illustrated | Illustrated |
| indexdate | 2024-07-09T19:03:21Z |
| institution | BVB |
| isbn | 0121995046 |
| language | English |
| lccn | 2001098272 |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-009891754 |
| oclc_num | 49780706 |
| open_access_boolean | |
| owner | DE-355 DE-BY-UBR DE-11 |
| owner_facet | DE-355 DE-BY-UBR DE-11 |
| physical | XXVIII, 677 S. Ill., graph. Darst. |
| publishDate | 2002 |
| publishDateSearch | 2002 |
| publishDateSort | 2002 |
| publisher | Acad. Press |
| record_format | marc |
| spelling | Adenoviral vectors for gene therapy ed. by David T. Curiel ... Amsterdam [u.a.] Acad. Press 2002 XXVIII, 677 S. Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier Includes bibliographical references Adenoviridae ram Adenovírus larpcal Adénovirus Genes virais larpcal Thérapie génique Thérapie génique ram Vecteurs de clonage ram Vírus de dna larpcal Adenoviridae Adenoviruses Gene Therapy methods Gene therapy Genetic Vectors therapeutic use Gentherapie (DE-588)4296957-8 gnd rswk-swf Adenoviren (DE-588)4141412-3 gnd rswk-swf Adenoviren (DE-588)4141412-3 s Gentherapie (DE-588)4296957-8 s DE-604 Curiel, David 19XX- (DE-588)122647828X edt HBZ Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=009891754&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Adenoviral vectors for gene therapy Adenoviridae ram Adenovírus larpcal Adénovirus Genes virais larpcal Thérapie génique Thérapie génique ram Vecteurs de clonage ram Vírus de dna larpcal Adenoviridae Adenoviruses Gene Therapy methods Gene therapy Genetic Vectors therapeutic use Gentherapie (DE-588)4296957-8 gnd Adenoviren (DE-588)4141412-3 gnd |
| subject_GND | (DE-588)4296957-8 (DE-588)4141412-3 |
| title | Adenoviral vectors for gene therapy |
| title_auth | Adenoviral vectors for gene therapy |
| title_exact_search | Adenoviral vectors for gene therapy |
| title_full | Adenoviral vectors for gene therapy ed. by David T. Curiel ... |
| title_fullStr | Adenoviral vectors for gene therapy ed. by David T. Curiel ... |
| title_full_unstemmed | Adenoviral vectors for gene therapy ed. by David T. Curiel ... |
| title_short | Adenoviral vectors for gene therapy |
| title_sort | adenoviral vectors for gene therapy |
| topic | Adenoviridae ram Adenovírus larpcal Adénovirus Genes virais larpcal Thérapie génique Thérapie génique ram Vecteurs de clonage ram Vírus de dna larpcal Adenoviridae Adenoviruses Gene Therapy methods Gene therapy Genetic Vectors therapeutic use Gentherapie (DE-588)4296957-8 gnd Adenoviren (DE-588)4141412-3 gnd |
| topic_facet | Adenoviridae Adenovírus Adénovirus Genes virais Thérapie génique Vecteurs de clonage Vírus de dna Adenoviruses Gene Therapy methods Gene therapy Genetic Vectors therapeutic use Gentherapie Adenoviren |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=009891754&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT curieldavid adenoviralvectorsforgenetherapy |