Molecular Therapeutics 21st Century Medicine

, by Greenwell, Pamela; McCulley, Michelle

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ISBN: 9780470019160 | 0470019166
Cover: Hardcover
Copyright: 12/17/2007

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"This book should be useful to lecturers who teach senior undergraduates, graduate students, and students in the biomedical sciences in general. More globally, Greenwell and McCulley's book should encourage academicians of any stripe who for some time have been honing their lectures in a niche subject area to turn their courses into textbooks." -Biochemistry and Molecular Biology EducationMolecular therapeutics refers to the developments in molecular biology that are focused on treating disease with new molecular-based drugs.By taking advantage of recent advances and increased understanding in the field of human genetics, this book provides essential background knowledge and key literature on a broad range of novel approaches and disciplines. These include making recombinant proteins, xenotransplantation gene therapy and therapeutic cloning. Molecular Therapeutics: 21st Century Medicine describes the techniques - including their associated benefits, problems, pitfalls - and discusses their applicability with respect to treating microbial, inherited, multifactoral and acquired diseases. The book also pays specific attention to the ethical issues associated with this new field. Cutting-edge topics and clinically relevant materials engage and maintain student interest Self-assessment questions are included throughout the book Features an additional web site, with a web forum, regular updates and PowerPoint slides of figures from the bookMolecular Therapeutics: 21st Century Medicine is a comprehensive, accessible and engaging guide to the rapidly developing field of molecular therapeutics. It is essential reading for all students in this area of research and also of interest for health professionals involved in these novel therapies.

Prologue	p. xi
Introduction	p. 1
Microbial diseases	p. 2
Cancer and heart disease	p. 3
Cancer	p. 4
Heart disease	p. 5
Genetic diseases	p. 5
Dominant diseases	p. 6
Recessive diseases	p. 6
Role of molecular biology in therapeutics	p. 7
Prenatal diagnosis and pre-implantation	p. 11
Should we treat inherited diseases?	p. 11
Genetic screening	p. 12
Pre-implementation genetic diagnosis	p. 13
Counselling	p. 15
Simple protein replacement therapy	p. 17
Preventing transfusion-transmissible infectious diseases in the UK	p. 18
Ensuring the safety of organ transplants	p. 19
Preventing transfusion-transmissible infectious diseases worldwide	p. 20
HIV	p. 20
Recombinant protein production	p. 23
Choice of organism	p. 23
Somatostatin: an example of protein produced in E. coli	p. 27
Insulin: an example of a recombinant protein	p. 27
Alternatives to E. coli for the production of recombinant proteins	p. 29
Insect cells	p. 29
Whole insects	p. 30
Mammalian cells	p. 30
Plants	p. 30
Transgenic animals	p. 31
Problems with recombinant protein production	p. 31
Problems with glycosylation	p. 32
Effect of glycosylation	p. 33
Erythropoietin: an example of protein produced in mammalian cells	p. 35
Production method	p. 36
Preparation of Factor VIII	p. 36
Transgenic pigs and Factor VIII	p. 37
All recombinants must be tested before they are given to humans	p. 38
Why make recombinant proteins?	p. 39
Recombinant products	p. 40
Generics	p. 40
Recombinant vaccines	p. 43
Vaccine history	p. 43
Vaccines	p. 45
Vaccine methods	p. 46
Types of vaccine	p. 47
The limitations of vaccine programmes	p. 48
The role of the WHO	p. 50
Problems specific to developing countries	p. 51
Economics and logistics of vaccinology	p. 52
Recombinant vaccines	p. 54
Simple recombinant protein vaccines	p. 55
Gene vaccines: the vaccinia virus approach	p. 57
DNA vaccines	p. 57
Edible vaccines from transgenic plants	p. 58
Rational design: bioinformatics and proteomics	p. 59
Other interesting area for vaccine development	p. 60
Conclusion	p. 60
Therapeutic antibodies and immunotherapy	p. 63
Monoclonal antibodies	p. 63
Monoclonal production	p. 64
Therapeutic monoclonal antibodies	p. 66
Human monoclonals	p. 66
Humanised antibodies	p. 67
Transgenic monoclonals	p. 69
The uses of monoclonal antibodies in therapy	p. 69
Specific examples of therapeutic strategies	p. 70
Unconjugated antibodies - treatment of kidney rejection	p. 70
HIV treatment	p. 71
Cancer therapy and monoclonal antibodies	p. 71
Herceptin in breast cancer therapy	p. 71
Treatment of multi-drug-resistant cancer cells	p. 72
Anti-endotoxin antibodies	p. 73
Conjugated antibodies	p. 73
Delivery of radionuclides to leukaemia and lymphoma patients	p. 74
Drug delivery	p. 74
Toxin delivery	p. 75
Bispecific antibodies	p. 75
Other recombinant proteins used in immunotherapy	p. 76
Cytokines	p. 76
Colony-stimulating factors and growth factors	p. 79
Transgenic animals	p. 83
Why do we want to engineer the genomes of animals?	p. 83
Experimental procedure	p. 85
Method 1: Germline manipulation	p. 85
Method 2: Using embryonic stem cells	p. 87
DNA constructs, insertional mutagenesis and homologous recombination	p. 90
Uses of inducible and tissue-specific promoters	p. 91
Introduction of the DNA into the cells	p. 92
Uses of transgenics	p. 93
Recombinant protein production	p. 93
Animal models of human diseases	p. 94
Transplantation: a form of gene therapy	p. 99
Introduction	p. 99
Bone marrow	p. 100
Logistical problems with BMT	p. 102
Solid organ transplantation	p. 102
Heart transplantation	p. 103
Lung	p. 104
Kidney	p. 105
Liver	p. 105
Ovarian tissue	p. 106
Other cells and tissues	p. 106
Summary of the problems associated with transplantation	p. 107
Transplantation statistics	p. 108
Legislation	p. 108
Religious beliefs and transplantation	p. 110
Xenotransplantation	p. 113
Introduction	p. 113
Rationale for the use of non-human donors	p. 114
Organs from non-human primates	p. 114
Pigs	p. 115
Can we pretreat the recipient to prevent rejection?	p. 116
Problems with pigs	p. 117
Will pig hearts function in humans?	p. 117
Xenozoonoses	p. 117
Religious objections	p. 118
Animal activists	p. 119
Government legislation	p. 119
When will xenotransplantation start?	p. 120
Patient attitudes	p. 120
Ethics	p. 121
Alternatives to xenotransplants	p. 121
Reproductive cloning	p. 125
History	p. 125
Problems	p. 127
Why was there so much interest in Dolly?	p. 128
Was Dolly a lone example?	p. 129
Why is cloning useful?	p. 129
Is human cloning a reality?	p. 130
Why can we not produce human clones that are identical?	p. 131
So why clone humans?	p. 132
What are the ethical and moral problems?	p. 132
Stem cell therapy	p. 137
The potency of cells	p. 137
Cloning	p. 137
Potency of stem cells	p. 138
Potential sources of stem cells	p. 138
Stem cells and therapeutic cloning	p. 138
Legislation and therapeutic cloning	p. 140
Other sources of stem cells	p. 142
What can be done?	p. 142
Experiments on embryonic cells	p. 143
Experiments on fetal tissue and cord blood	p. 143
Stem cells from adult tissues	p. 143
Safety and technical problems	p. 144
Perceived scope of therapy	p. 145
Clinical trials of stem cell therapy	p. 145
What are the future prospects for stem cell research?	p. 146
Gene augmentation therapy	p. 149
Introduction	p. 149
Strategy	p. 150
DNA delivery	p. 151
Viral vectors and gene therapy	p. 152
Artificial viruses	p. 155
Non-viral delivery in gene therapy	p. 155
What tissues can we currently target?	p. 157
Targeting gene expression	p. 159
Problems associated with augmentation therapy	p. 160
Gene augmentation therapy vs. recombinant DNA therapy or transplantation	p. 161
Current criteria for the use of gene therapy	p. 162
The bystander effect	p. 163
Candidates for gene therapy	p. 163
Gene therapy trials for inherited diseases	p. 165
Introduction	p. 165
Examples of disease treated with retroviral gene therapy	p. 166
Severe combined immunodeficiency	p. 166
Hypercholesterolaemia	p. 169
Cystic fibrosis	p. 170
Rationale for adenoviral vectors	p. 171
Early animal trials	p. 171
Is CF gene therapy 'safe but not useful'?	p. 172
Problems also found in in vivo delivery	p. 172
Animal trials with Factor IX	p. 173
Adenoviruses have also been used to introduce genes into brain	p. 174
Duchenne's muscular dystrophy	p. 175
Problems with adenoviruses	p. 175
The uses of adeno-associated viruses	p. 176
Haemophilia B treatment with Factor IX gene augmentation	p. 176
AAV therapy for DMD	p. 177
Liposome vector trials	p. 178
Trials with polymer mareix delivery	p. 178
Gene silencing technologies	p. 181
Antisense therapy	p. 181
Modification of antisense molecules	p. 183
Replacement of oxygens in the phosphate bridge	p. 184
Modifications can be made to the bases themselves	p. 184
Other types of modifications	p. 185
The ideal oligonucleotide	p. 185
Uptake	p. 185
Uses of antisense oligonucleotides	p. 187
Examples	p. 187
Catalytic antisense molecules	p. 191
Triple helix (triplex) technology	p. 191
Problems	p. 193
Advantages over antisense strategies	p. 193
Experimental data	p. 194
Ribozymes	p. 196
Examples of ribozyme therapies	p. 197
Small interfering RNAs (siRNAs)	p. 198
Clinical trials and siRNA	p. 202
Is RNAi better than antisense?	p. 202
Gene therapy for cancer	p. 205
What causes cancer?	p. 205
Cancer: a multifactorial disease	p. 206
Cancer statistics	p. 207
Best treatment currently available	p. 208
Avoidance	p. 208
Screening	p. 208
Surgery	p. 209
Chemotherapy	p. 209
Radiotherapy	p. 210
Do chemo- and radiotherapy cause problems?	p. 210
New cancer therapies	p. 210
Cancer models in animals	p. 211
What kinds of gene therapy can we use to treat cancer?	p. 212
Perceived problems in cancer gene augmentation therapy	p. 213
Killing cells with ganciclovir or suicide therapy	p. 213
Prodrug activation therapy	p. 214
Enhancing the immune system with gene therapy	p. 215
Gene silencing technologies and cancer	p. 217
Conclusion	p. 219
Single-nucleotide polymorphisms (SNPs) and therapy	p. 223
Legislation, clinical trials and ethical issues	p. 231
Legislative bodies	p. 231
Clinical trials	p. 233
The problems of placebo controlled trials	p. 236
The need for informed consent	p. 238
Trials in developing countries	p. 239
Recent trial issues	p. 241
Conclusion	p. 242
Epilogue	p. 245
Sourcing references	p. 245
Index	p. 247
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Molecular Therapeutics 21st Century Medicine

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