Molecular and Cell Biology of Human Gene Therapeutics

418 Pages·1995·11.453 MB·English

by  Ariberto Fassati, Matthew G. Dunckley (auth.), George Dickson (eds.)

Molecular and Cell Biology of
Human Gene Therapeutics
Molecular and Cell Biology of Human Diseases Series
Series Editors
D.J.M. WRIGHT MD FR CPath
Reader in Medical Microbiology,
Charing Cross and Westminster School, London, UK
L.c. ARCHARD PhD
Senior Lecturer in Biochemistry,
Charing Cross and Westminster Medical School, London, UK
The continuing developments in molecular biology have made possible a
new approach to a whole range of different diseases. The books in this series
each concentrate on a disease or group of diseases where real progress is
being made in understanding the pathogenesis, diagnosis and management.
Experts on aspects of each area provide a text accessible to scientists and
clinicians in a form which records advances and points to the potential
application of these advances in a clinical setting.
Other titles in this series
1 Molecular and Cell Biology of Sexually Transmitted Diseases
Edited by David Wright and Leonard Archard
2 Molecular and Cell Biology of Opportunistic Infections in AIDS
Edited by Steven Myint and Alan Cann
3 Molecular and Cell Biology of Muscular Dystrophy
Edited by Terence Partridge
4 Molecular and Cell Biology of Neuropsychiatric Diseases
Edited by Frank Owen and Ruth Itzhaki
Molecular and Cell Biology of
Human Gene Therapeutics
EDITED BY
George Dickson
Department of Biochemistry,
Royal Holloway, University of London, UK
CHAPMAN &. HALL
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First edition 1995
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Contents
List of contributors Xl
1 Retroviral vectors 1
ARIBERTO FASSATI, MATTHEW G. DUNCKLEY
and GEORGE DICKSON
1.1 Introduction 1
1.2 The retroviral genome 2
1.3 The retrovirallife cycle 4
1.4 The design of retroviral vectors 8
1.5 Packaging cell lines 12
1.6 Safety considerations 14
References 15
2 Adenoviral vectors 20
MARTIN G. LEE, ERIC J. KREMER and MICHEL PERRICAUDET
2.1 Introduction 20
2.2 Adenovirus structure 21
2.3 Mechanism of virus entry and delivery to the nucleus 22
2.4 Molecular biology of adenovirus 24
2.5 Advantages of adenovirus as gene therapy vectors 25
2.6 Adenovirus gene therapy and the immune response 27
2.7 Conclusions 29
Acknowledgements 30
References 30
3 Herpes simplex virus vectors 33
JOSEPH GLORIOSO, MARY ANN BENDER, DAVID FINK
and NEAL DELUCA
3.1 Introduction 33
3.2 Engineering herpes simplex virus vectors 35
3.3 Removal of cytotoxic genes 45
v
CONTENTS
3.4 Expression of therapeutic genes 47
3.5 Conclusions 57
References 58
4 Liposome-mediated gene transfer 64
ITARU YANAGIHARA, YASUFUMI KANEDA, KO]I INUI
and SHINTARO OKADA
4.1 Introduction 64
4.2 Basic aspects of liposomes 65
4.3 Conventionalliposome systems 69
4.4 Hemagglutinating virus of Japan (HVJ or Sendai virus) -
liposomes 72
4.5 Future prospects for liposome-mediated gene therapy 78
References 80
5 Intramuscular injection of plasmid DNA 83
DOMINIC J. WELLS
5.1 Introduction 83
5.2 Plasmid preparation and transfer 84
5.3 Physiological status of recipient muscle 90
5.4 The mechanism of plasmid uptake by myofibers 96
5.5 Longevity of plasmid expression 97
5.6 Gene therapy applications for intramuscular plasmid
gene transfer 98
5.7 Other applications for intramuscular plasmid gene
transfer 99
5.8 Conclusions 100
References 101
6 Yeast artificial chromosome vectors 104
STEWART A. FABB and JIANNIS RAGOUSSIS
6.1 Introduction 104
6.2 YAC vectors 104
6.3 YAC modification 105
6.4 Introduction of YA Cs into mammalian cells 112
6.5 Mammalian artificial chromosomes 119
6.6 Conclusions 121
References 121
7 Gene transfer and cancer chemotherapy 125
DONALD W. MOORMAN and KENNETH W. CULVER
7.1 Introduction 125
7.2 Marking cells to study safety, survival and trafficking 126
VI
CONTENTS
7.3 T-lymphocyte gene manipulation and cancer
immunotherapy 127
704 Tumor cell gene manipulation and cancer
immunotherapy 127
7.5 Cytotoxic gene delivery systems 131
7.6 Targeting the genetic basis of malignant transformation 137
7.7 Conclusions 137
References 13 7
8 Vaccine immunotherapy for cancer 140
JOHN BRIDGEWATER and MARY COLLINS
8.1 Introduction 140
8.2 Background 141
8.3 Virus and hapten modified vaccine 142
804 Genetically modified tumor vaccines 144
8.5 Human trials using tumor vaccines 148
8.6 Tumor antigens and co-stimulation 148
8.7 Future prospects 149
References 152
9 Inherited immunodeficiencies 157
CHRISTINE KINNON
9.1 Introduction 157
9.2 Severe combined immunodeficiency 160
9.3 Chronic granulomatous disease 164
9 A Leukocyte adhesion deficiency 166
9.5 X-linked agammaglobulinemia 167
9.6 X-linked agammaglobulinemia with hyper IgM syndrome 168
9.7 Properdin deficiency 169
9.8 Future prospects 170
Acknowledgements 171
References 172
10 Anti-viral strategies 175
MARINEE K.L. CHUAH, THIERRY VANDENDRIESSCHE and
RICHARD A. MORGAN
10.1 Introduction 175
10.2 Anti-viral gene therapy strategies 176
10.3 Gene therapy for viral diseases 181
lOA Prospects for anti-viral gene therapy 190
Acknowledgements 191
References 191
Vll
CONTENTS
11 AIDS and HIV infection 195
CLA Y SMITH and BRUCE A. SULLENGER
11.1 Introduction 195
11.2 Biology of HIV infection 195
11.3 Current therapy of HIV infection 199
11.4 Strategies for treating HIV with gene therapy 201
11.5 Gene delivery systems for gene therapy of HIV infection 213
11.6 Preclinical and clinical evaluation of gene therapy
approaches for treating HIV infection 217
11.7 Conclusions 226
References 227
12 Cystic fibrosis and lung diseases 237
SAMUEL c. WADSWORTH and ALAN E. SMITH
12.1 Introduction 237
12.2 Gene therapy for cystic fibrosis 238
12.3 Target cells in the lung for cystic fibrosis therapy 239
12.4 Vectors for cystic fibrosis gene therapy 239
12.5 Clinical trials with cystic fibrosis gene therapy vectors 247
12.6 Conclusions 249
Acknowledgements 249
References 250
13 Arthritis 252
CHRISTOPHER H. EVANS and PAUL D. ROBBINS
13.1 Introduction 252
13.2 Local gene delivery to diseased joints 253
13.3 Systemic gene delivery for arthritis 257
13.4 Conclusions and future directions 258
Acknowledgements 258
References 258
14 Duchenne muscular dystrophy 261
GEORGE DICKSON and SUSAN C. BROWN
14.1 Duchenne muscular dystrophy 261
14.2 The dystrophin gene 262
14.3 Dystrophin 264
14.4 Function of dystrophin in skeletal muscle 267
14.5 Therapeutic strategies for Duchenne muscular
dystrophy 268
14.6 Future perspectives 273
References 275
Vlll
CONTENTS
15 Cardiovascular disease 281
HOWARD PRENTICE and KEITH A. WEBSTER
15.1 Introduction 281
15.2 Therapeutic potential of gene transfer for cardiovascular
disease 281
15.3 Methods of arterial gene transfer 283
15.4 Analysis and control of vascular remodeling by
gene transfer 287
15.5 Applications of antisense oligonucleotides to models
of vascular disease 288
15.6 Grafting of retrovirally transduced endothelial
or smooth muscle cells onto injured arteries 288
15.7 Strategies for gene and cell therapy in the myocardium 289
15.8 Myocardial gene transfer using replication-defective
adenovirus 292
15.9 Transgenic studies 293
15.10 Future directions for cardiovascular gene transfer 294
References 296
16 Degenerative and inherited neurological disorders 301
PEDRO R. LOWENSTEIN
16.1 Introduction 301
16.2 Current status of therapeutic intervention in selected
neurological disorders 304
16.3 Candidate diseases for neurological gene therapy 310
16.4 Targeting foreign genes to the brain 319
16.5 Germ-line gene therapy 328
16.6 Future prospects and commercial development 329
Acknowledgements 332
References 332
Appendix 16.A 337
Appendix 16.B 348
Appendix 16.C 349
17 Mucopolysaccharidosis 350
OLIVIER DANOS and JEAN-MICHEL HEARD
17.1 Introduction 350
17.2 Molecular basis, physiopathology and current treatments 351
17.3 Strategies for gene therapy 356
17.4 Prospects for clinical trials 362
Acknowledgements 363
References 363
IX
CONTENTS
18 DNA-based immunization 368
HEATHER L. DA VIS and ROBERT G. WHALEN
18.1 Introduction 368
18.2 The response of the immune system to immunization 369
18.3 Limitations of current vaccination strategies 370
18.4 Potential advantages of nucleic acid vaccination 371
18.5 Animal models of DNA-based immunization 372
18.6 Immune response to DNA immunization 377
18.7 Future directions for DNA-based immunization 382
18.8 Summary 384
Acknowledgements 384
References 385
Index 388
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