Alain Rolland9780824742355, 0-8247-4235-4
Table of contents :
PHARMACEUTICAL GENE DELIVERY SYSTEMS……Page 1
PREFACE……Page 10
CONTENTS……Page 12
CONTRIBUTORS……Page 14
CONTENTS……Page 0
I. WHAT IS GENE THERAPY?……Page 17
II. DEVELOPMENT OF A GENE THERAPY PHARMACEUTICAL……Page 21
A. PRODUCT DISCOVERY……Page 23
1. DOSE OPTIMIZATION……Page 24
2. STABILITY……Page 25
3. SAFETY/ TOXICITY……Page 26
4. SCALE UP AND VALIDATION OF MANUFACTURING……Page 27
C. IND SUBMISSION……Page 28
D. CLINICAL TRIALS……Page 30
REFERENCES……Page 31
I. INTRODUCTION……Page 33
2. PLASMID DNA VECTORS……Page 34
3. PLASMID-BASED TRANSPOSONS……Page 35
4. REPLICATING VECTORS AND NUCLEAR RETENTION……Page 36
C. SIMIAN VIRUS VECTORS……Page 38
A. VIRAL PROMOTERS: CMV……Page 39
B. CELLULAR PROMOTERS……Page 42
C. SYNTHETIC PROMOTERS……Page 44
IV. REDUCING THE IMMUNE RESPONSE TO INCREASE DURATION OF EXPRESSION……Page 45
2. INHIBITING THE INNATE IMMUNE RESPONSE……Page 46
3. DISRUPTING T-CELL – ANTIGEN-PRESENTING CELL INTERACTIONS……Page 47
C. DECREASING THE IMMUNOGENICITY OF THE VECTOR……Page 48
2. PARTIALLY AND FULLY DELETED AD VECTORS……Page 49
3. DECREASED IMMUNE RESPONSE TO AAV VECTORS AND LENTIVIRAL VECTORS……Page 50
4. PLASMID DNA VECTORS……Page 51
REFERENCES……Page 52
A. WHY DRUG-REGULATED GENE TRANSFER?……Page 63
A. DESCRIPTION……Page 64
C. VIRUS-BASED GENE TRANSFER STUDIES……Page 67
D. SUMMARY……Page 68
A. DESCRIPTION……Page 69
B. PLASMID-BASED GENE TRANSFER STUDIES……Page 70
C. VIRUS-BASED GENE TRANSFER STUDIES……Page 71
A. DESCRIPTION……Page 72
C. VIRUS-BASED GENE TRANSFER STUDIES……Page 76
D. SUMMARY……Page 77
A. DESCRIPTION……Page 78
B. PLASMID-BASED GENE TRANSFER STUDIES……Page 80
D. SUMMARY……Page 84
A. BASAL EXPRESSION……Page 85
B. SINGLE VERSUS MULTIPLE VECTORS……Page 86
D. KINETICS……Page 87
E. DURATION……Page 88
G. IMMUNOGENICITY AND TOXICITY……Page 89
VII. SUMMARY……Page 90
REFERENCES……Page 91
I. CATIONIC LIPIDS IN GENE TRANSFER……Page 95
A. DEVELOPMENT OF CATIONIC LIPID FORMULATIONS……Page 97
II. NAKED DNA MEDIATES GENE TRANSFER……Page 99
A. PROTECTION/ STABILITY IN PHYSIOLOGICAL MEDIUM……Page 100
1. EFFECT OF CHARGE RATIO AND SIZE/ SEDIMENTATION……Page 101
C. INTERNALIZATION/ ENDOSOMAL ESCAPE……Page 102
D. NUCLEAR ENTRY……Page 104
A. LUNG ANATOMICAL AND PHYSIOLOGICAL CONSIDERATIONS……Page 106
B. IN VIVO DISTRIBUTION: INTRAVENOUS ADMINISTRATION……Page 111
C. IN VIVO DISTRIBUTION: INTRATRACHEAL ADMINISTRATION……Page 113
V. TOXICITY ASSOCIATED WITH CATIONIC LIPID GENE DELIVERY……Page 115
VI. SUMMARY……Page 117
REFERENCES……Page 118
I. INTRODUCTION……Page 125
A. INTRINSIC PROPERTIES OF POLYCATIONS (DNA CONDENSATION, COMPLEX UPTAKE, AND ENDOSOMAL RELEASE)……Page 127
1. POLYLYSINE-BASED VECTORS……Page 128
2. STARBURST DENDRIMERS AND POLYETHYLENIMINE-BASED VECTORS……Page 130
B. MIGRATION THROUGH THE CYTOPLASM AND NUCLEAR ENTRY……Page 131
C. RECEPTOR-MEDIATED GENE DELIVERY……Page 132
III. LOCAL APPLICATION IN VIVO……Page 134
IV. SYSTEMIC APPLICATION……Page 135
A. SYSTEMICALLY DELIVERED POLYLYSINE/ DNA COMPLEXES……Page 136
C. SHIELDING OF POLYCATION COMPLEXES……Page 137
D. TARGETED GENE EXPRESSION WITH SHIELDED POLYPLEXES……Page 138
V. SUMMARY……Page 140
REFERENCES……Page 141
I. INTRODUCTION……Page 152
II. DEVELOPMENT OF HVJ-LIPOSOMES……Page 153
IV. IMPROVEMENT OF THE CURRENT VECTOR SYSTEM……Page 155
A. SUSTAINED GENE EXPRESSION IN VITRO AND IN VIVO BY THE EBV REPLICON VECTOR COUPLED WITH HVJ-LIPOSOMES……Page 158
B. ENHANCEMENT OF TRANSGENE EXPRESSION BY EBNA-1……Page 159
REFERENCES……Page 161
I. INTRODUCTION……Page 164
II. BIOLOGY OF ADENOVIRUSES……Page 165
III. FIRST-GENERATION AD VECTORS……Page 166
A. CONSTRUCTION AND PROPAGATION OF FIRST-GENERATION VIRUSES……Page 167
1. GENETIC DISEASE……Page 169
2. CANCER GENE THERAPY……Page 170
3. OTHER APPLICATIONS……Page 172
IV. SECOND-GENERATION AD VECTORS……Page 173
V. FULLY DELETED AD VECTORS……Page 174
A. PROPAGATION OF FDADS……Page 175
B. SIZE CONSTRAINTS AND THE IMPORTANCE OF STUFFER DNA……Page 177
C. IN VITRO AND IN VIVO STUDIES……Page 178
D. READMINISTRATION OF FDADS……Page 179
E. RECENT ADVANCES IN VECTOR DESIGN……Page 180
VII. SUMMARY……Page 182
REFERENCES……Page 183
I. INTRODUCTION……Page 198
B. MOLECULAR BIOLOGY AND REPLICATION……Page 199
C. LATENCY……Page 201
A. DESIGN……Page 202
B. PRODUCTION……Page 203
1. COMPLEMENTATION SYSTEMS……Page 204
3. PURIFICATION……Page 206
4. ASSAY……Page 207
IV. GENERAL PROPERTIES OF AAV VECTORS……Page 208
A. CELLULAR BINDING AND TRAF.CKING……Page 209
B. DNA METABOLISM……Page 210
C. DUAL VECTORS……Page 212
D. HOST RESPONSES AND TOXICITY……Page 213
A. CYSTIC FIBROSIS……Page 215
B. HEMOPHILIA……Page 217
REFERENCES……Page 218
I. INTRODUCTION……Page 229
1. RETROVIRAL COMPONENTS……Page 231
2. RETROVIRAL MACHINERY……Page 232
1. FINDING THE WAY TO THE NUCLEUS……Page 233
2. PRODUCTION SUPPLY……Page 234
1. TRANS GIVING……Page 235
2. CIS REQUIRED……Page 237
3. VIRAL FACTORIES……Page 238
A. ENVELOPE MODI.CATIONS……Page 240
1. MITOSIS: A LICENSE FOR INTEGRATION……Page 242
2. UNLOCKING THE NUCLEUS WITH LENTIVIRAL VECTORS: WHAT MAKES THE DIFFERENCE?……Page 243
C. THERAPEUTIC EXPRESSION……Page 245
IV. COLLATERAL DAMAGES……Page 246
NOTE ADDED IN PROOF……Page 248
REFERENCES……Page 249
I. INTRODUCTION……Page 259
II. NEEDLE-FREE PARTICLE-MEDIATED GENE DELIVERY……Page 260
A. NEEDLE-FREE DEVICES……Page 261
B. ISSUES ASSOCIATED WITH NEEDLE-FREE DELIVERY OF DNA PLASMID……Page 264
1. GENETIC VACCINATION……Page 266
2. GENE REPLACEMENT……Page 270
III. CELL MEMBRANE – PERMEABILIZING GENE DELIVERY TECHNIQUES……Page 271
1. REGIMEN AND DELIVERY PARAMETERS……Page 272
2. ELECTRODE TYPE……Page 275
3. CELL AND TISSUE ELECTROTRANSFECTION……Page 276
IV. SONOPORATION……Page 283
V. SUMMARY……Page 285
REFERENCES……Page 286
I. INTRODUCTION……Page 293
A. CLINICAL TRIAL UPDATE FOR NONVIRAL VECTORS IN CANCER GENE THERAPY……Page 294
A. TARGETING GENETIC DEFECTS THAT LEAD TO GROWTH ADVANTAGE……Page 296
1. DOWNREGULATION OF ONCOGENE OR PROTO-ONCOGENE……Page 297
2. RESTORATION OF GROWTH REGULATION……Page 301
3. INHIBITION OF ANGIOGENESIS……Page 302
1. ENHANCEMENT OF TUMOR IMMUNOGENICITY……Page 304
2. MODIFICATION OF IMMUNE EFFECTORS……Page 305
4. REVERSAL OF TUMOR-INDUCED IMMUNOSUPPRESSION……Page 306
1. INTRODUCTION OF A TOXIC GENE……Page 307
2. INTRODUCTION OF A CHEMOSENSITIZING GENE……Page 309
A. NAKED DNA……Page 310
B. GENE GUN……Page 312
C. LIPIDIC VECTORS……Page 313
D. POLYMER……Page 316
A. IMPROVING TRANSFECTION EF.CIENCY……Page 318
C. SPECIFIC TARGETING……Page 319
D. MINIMIZING TOXICITY……Page 320
VI. SUMMARY……Page 322
REFERENCES……Page 323
I. INTRODUCTION……Page 334
II. FUNCTIONS ENCODED IN ADENOVIRAL E1 REGION……Page 335
IV. COMPLEMENTATION OF E1A FUNCTIONS BY DEREGULATED E2F IN TUMOR CELLS……Page 337
V. TUMOR-SPECIFIC EXPRESSION OF E1A AND OTHER EARLY VIRAL PROTEINS……Page 339
VII. CONDITIONAL EXPRESSION OF DOMINANTNEGATIVE INHIBITOR TO CONFER SELECTIVITY……Page 341
VIII. MODIFICATION OF THE VIRAL GENOME TO ENHANCE ONCOLYTIC ACTIVITY……Page 343
IX. THERAPEUTIC GENES IN REPLICATING ADENOVIRAL VECTORS……Page 344
X. CAPSID MODIFICATION TO ALTER THE TROPISM OF REPLICATING ADENOVIRAL VECTORS……Page 345
XI. INDUCED REPLICATION OF E1-DELETED VECTORS BY COMPLEMENTATION OF E1 PROTEINS IN WITH REPLICATING ADENOVIRUSES……Page 346
XII. CLINICAL TRIALS WITH AN E1B-55K – DELETED VECTOR BY ONYX PHARMACEUTICALS……Page 347
XV. CLINICAL STUDIES WITH OTHER ONCOLYTIC VIRUSES……Page 349
REFERENCES……Page 350
II. VECTOR REQUIREMENTS FOR VASCULAR GENE TRANSFER……Page 357
A. LOCAL INTRAVASCULAR GENE DELIVERY……Page 358
A. THERAPEUTIC ANGIOGENESIS……Page 359
B. RESTENOSIS……Page 362
D. STENTS……Page 363
A. PERIPHERAL VASCULAR DISEASE……Page 364
VII. SAFETY ASPECTS……Page 365
REFERENCES……Page 366
II. ROUTE OF ADMINISTRATION……Page 375
C. INTRAMUSCULAR INJECTION……Page 376
III. BARRIERS TO GENE EXPRESSION IN THE AIRWAY……Page 377
B. CELL SURFACE AND RECEPTORS……Page 378
D. IMMUNE SYSTEM……Page 379
A. CYSTIC FIBROSIS……Page 380
B. REQUIRED DEGREE OF GENE TRANSFER……Page 382
C. ASSESSMENT OF EFFICACY……Page 383
A. PRECLINICAL STUDIES……Page 384
1. ADENOVIRAL VECTORS……Page 385
3. SYNTHETIC VECTORS……Page 387
2. HUMAN TRIALS……Page 389
1. TUMOR-SUPPRESSOR GENE THERAPY……Page 390
3. IMMUNOTHERAPY……Page 391
1. ACUTE LUNG INJURY……Page 392
3. FIBROTIC LUNG DISEASE……Page 394
4. LUNG TRANSPLANTATION……Page 395
REFERENCES……Page 396
A. ORIGINS……Page 409
C. CENTROMERES……Page 410
B. BACTERIAL ARTIFICIAL CHROMOSOMES……Page 412
C. P1-DERIVED ARTIFICIAL CHROMOSOMES……Page 413
1. EPISOMAL EBV/ BAC – BASED MACS……Page 414
A. PHYSICAL MAPPING……Page 415
B. ANIMAL TRANSGENESIS……Page 416
A. MAC TOP-DOWN ASSEMBLY……Page 417
B. MAEC BOTTOM-UP ASSEMBLY……Page 418
VI. SUMMARY……Page 420
REFERENCES……Page 422
Reviews
There are no reviews yet.