Publications by Biophoenix' Principals

Biotechnology Made Simple IV
Publisher:PJB Publications Ltd
Year of publication:1991
Type of publication:Management report
Publisher's reference (if any):BS 322
Author(s):Sreten Bogdanovic
Approximate page count:250
Price when published:£300
Remarks:
  1. Page numbers, where given, refer to the draft manuscript (which may differ from the published version).
  2. The copyright in this report is owned by the publisher, to whom any requests for copies should be addressed.
                B I O T E C H N O L O G Y   M A D E   S I M P L E
                                       
                           Fourth edition (May 1991)
                                       
                                C O N T E N T S
                                       
        PREFACE                                                     ii
        CONTENTS                                                   iii
        FIGURES                                                   viii
        
        PART I - OVERVIEW OF BIOTECHNOLOGY AND MOLECULAR BIOLOGY
        
          1.1  The Structure of DNA                                  1.1
          
          1.2  Mendelian Genetics                                    1.2
             1.2.1  The Work of Mendel                               1.2
             1.2.2  The Behaviour of Genes                           1.2
             1.2.3  Genetic Linkage and Chromosomes                  1.5
             1.2.4  Classical Recombination                          1.6
             1.2.5  Applications of Linkage Analysis                 1.6
             1.2.6  Use of Genetic Markers                           1.7
             1.2.7  Genetic Mapping                                  1.9
             1.2.8  Gene Mapping in Human Beings                     1.10
               1.2.8.1  Cell Line Repositories                       1.10
               1.2.8.2  Cytogenetics                                 1.11
               1.2.8.3  In situ Nucleic Acid Hybridisation           1.11
               1.2.8.4  Interspecies Somatic Cell Hybridisation      1.12
               1.2.8.5  Physical disruption of DNA                   1.13
             1.2.9  What Exactly is a Gene?                          1.13
             1.2.10  Genes and Chromosomes                           1.15
             1.2.11  Extra-Chromosal DNA - plasmids                  1.16
          
          1.3  How Nucleic Acids Store and Transmit Information      1.16
             1.3.1  DNA Replication                                  1.16
             1.3.2  The Role of RNA                                  1.17
             1.3.3  DNA and RNA Sequencing                           1.19
             1.3.4  Transcription of DNA to RNA                      1.20
             1.3.5  Translation of mRNA into Protein                 1.21
             1.3.6  The Genetic Code                                 1.22
             1.3.7  A Second Genetic Code?                           1.23
             1.3.8  Mutations                                        1.23
          
          1.4  DNA Probes                                            1.25
             1.4.1  Introduction                                     1.25
             1.4.2  Applications of DNA Probes                       1.25
             1.4.3  DNA Probe Labels                                 1.27
             1.4.4  Use of DNA Probes in Diagnostics                 1.27
               1.4.4.1  Oligonucleotide (`Short') Probes             1.27
               1.4.4.2  Long (Genomic or cDNA) Probes and RFLPs      1.28
               1.4.4.3  Southern Blotting                            1.29
               1.4.4.4  DNA Fingerprinting                           1.29
               1.4.4.5  DNA Amplification - The Polymerase
                        Chain Reaction                               1.31
                  1.4.4.5.1  Introduction                            1.31
                  1.4.4.5.2  Power of PCR                            1.31
                  1.4.4.5.3  Performing the PCR                      1.32
                  1.4.4.5.4  Non-diagnostic Applications of PCR      1.34
                  1.4.4.5.5  Current Position of PCR                 1.35
          
          1.5  Recombinant DNA Technology                            1.35
             1.5.1  Introduction                                     1.35
             1.5.2  Production of the Gene                           1.36
             1.5.3  Incorporation of the Gene into a Vector          1.38
             1.5.4  Plasmid vectors                                  1.38
             1.5.5  Transfer of the Vector into a Host               1.39
             1.5.6  Selection of Bacteria Carrying the Plasmid       1.40
             1.5.7  Extraction of the protein                        1.41
             1.5.8  Expression of the Gene                           1.41
             1.5.9  Extraction of the Protein                        1.42
             1.5.10  Scale-up                                        1.43
             1.5.11  Expression in organisms other than E. coli      1.45
               1.5.11.1  Why do we need other Expression Systems?    1.45
               1.5.11.2  Expression in Yeast                         1.45
               1.5.11.3  Expression in Cultured Mammalian Cells      1.46
               1.5.11.4  Expression in Plant Systems                 1.47
               1.5.11.5  Gene Expresssion in Transgenic Mammals      1.48
             1.5.12  Protein Engineering                             1.49
               1.5.12.1  Introduction                                1.49
               1.5.12.2  Oligonucleotide-Directed Mutagenesis        1.49
               1.5.12.3  Chemical Modification of Proteins           1.50
               1.5.12.4  Modified Antibodies                         1.51
          
          1.6  Molecular Biology of Cancer                           1.51
             1.6.1  Somatic and Germ-line Mutations                  1.51
             1.6.2  Transformation                                   1.52
             1.6.3  Oncogenes                                        1.52
             1.6.4  Functions of Oncogenes and their Products        1.54
             1.6.5  Inherited Cancers                                1.55
               1.6.5.1  Introduction                                 1.55
               1.6.5.2  The Retinoblastoma Paradigm                  1.56
               1.6.5.3  Other Deletion-associated Malignancies       1.57
               1.6.5.4  Anti-oncogenes                               1.57
             1.6.6  DNA Diagnosis of Cancer                          1.58
               1.6.6.1  Introduction                                 1.58
               1.6.6.2  bcr analysis                                 1.58
               1.6.6.3  B/T cell DNA analysis                        1.59
          
          1.7  Survey of Recombinant Pharmaceutical Products         1.60
             1.7.1  Alpha-1-antitrypsin                              1.60
             1.7.2  Recombinant Thrombolytics                        1.61
               1.7.2.1  Pro-Urokinase and Urokinase                  1.61
               1.7.2.2  Streptokinase and Eminase (tm)               1.62
               1.7.2.3  Tissue Plasminogen Activator                 1.63
             1.7.3  Colony Stimulating Factors                       1.64
               1.7.3.1  Introduction                                 1.64
               1.7.3.2  Interleukin-3                                1.64
               1.7.3.3  Granulocyte/Macrophage-Colony
                        Stimulating Factor                           1.65
               1.7.3.4  Granulocyte-Colony Stimulating Factor        1.66
               1.7.3.5  Macrophage-Colony Stimulating Factor         1.67
             1.7.4  Epidermal Growth Factor                          1.68
             1.7.5  Fibroblast Growth Factor                         1.69
             1.7.6  Erythropoietin (EPO)                             1.69
             1.7.7  Factor VIII                                      1.71
             1.7.8  Human Growth Hormone                             1.71
             1.7.9  Interferons                                      1.73
               1.7.9.1  Introduction                                 1.73
               1.7.9.2  Alpha-Interferon                             1.74
               1.7.9.3  Beta-Interferon                              1.76
               1.7.9.4  Gamma-Interferon                             1.76
             1.7.10  Interleukins                                    1.77
               1.7.10.1  Interleukins 1-alpha and 1-beta             1.77
               1.7.10.2  Interleukin 2                               1.78
               1.7.10.3  Interleukin 4                               1.79
               1.7.10.4  Interleukin 5                               1.79
               1.7.10.5  Interleukin 6                               1.80
               1.7.10.6  Interleukin 7                               1.80
             1.7.11  Insulin                                         1.80
             1.7.12  Proinsulin                                      1.82
             1.7.13  Nerve Growth Factor                             1.83
             1.7.14  Platelet-Derived Growth Factor                  1.83
             1.7.15  Superoxide Dismutase                            1.84
             1.7.16  Transforming Growth Factors                     1.85
             1.7.17  Tumour Necrosis Factors                         1.86
          
          1.8  Gene Therapy and Antisense Nucleic Acids              1.87
          
          1.9  Patents in Biomedicine                                1.88
             1.9.1  Introduction                                     1.88
             1.9.2  Types of Patentable Subject Matter               1.90
             1.9.3  Legal Tests of Patentability                     1.91
             1.9.4  Describing the Invention                         1.92
             1.9.5  Chemical and Pharmaceutical Inventions           1.92
             1.9.6  Patenting Natural Products                       1.92
             1.9.7  Patenting Living Organisms                       1.93
             1.9.8  Prospects in Patenting                           1.94
          
          1.10  Antibody-Related Biotechnologies                     1.95
             1.10.1  Introduction                                    1.95
             1.10.2  Humoral Immunity                                1.96
             1.10.3  The immunoglobulins                             1.96
             1.10.4  Immunoglobulin diversity                        1.98
             1.10.5  The secretion of antibodies                     1.98
             1.10.6  The Monoclonal Antibody Technique               1.99
             1.10.7  Applications of Monoclonal Antibodies           1.100
             1.10.8  Further Advances in Antibody Technology         1.102
               1.10.8.1  Human Monoclonal Antibodies                 1.102
               1.10.8.2  Chemically Modified Antibodies              1.102
               1.10.8.3  Immunoconjugates                            1.103
               1.10.8.4  Single-Domain Antibodies                    1.103
               1.10.8.5  Catalytic Antibodies                        1.104
             1.10.9  Therapeutic Applications of
                     Monoclonal and Modified Antibodies              1.105
               1.10.9.1  Monoclonal Antibodies and Cancer Therapy    1.105
               1.10.9.2  Monoclonal Antibodies as
                         Immunododulators                            1.107
                  1.10.9.2.1  Introduction                           1.107
                  1.10.9.2.2  Transplant Rejection                   1.107
                  1.10.9.2.3  Septicaemic Shock                      1.108
             1.10.10  Vaccination and Immunisation                   1.109
               1.10.10.1  Introduction                               1.109
               1.10.10.2  Anti-Idiotype Vaccines                     1.110
               1.10.10.3  Passive Immunisation                       1.111
             1.10.11  Recombinant Vaccines                           1.111
               1.10.11.1  AIDS                                       1.111
               1.10.11.2  Hepatitis A                                1.113
               1.10.11.3  Hepatitis B                                1.113
               1.10.11.4  Hepatitis C                                1.114
               1.10.11.5  Other Vaccines                             1.115
        
        PART II - GLOSSARY OF BIOTECHNOLOGY TERMS                    2.1
        
        PART III - BIOTECHNOLOGY COMPANY PROFILES
        
          3.1  Introduction                                          3.1
          3.2  Abbott Laboratories                                   3.1
          3.3  Allelix Biopharmaceuticals                            3.2
          3.4  Amgen                                                 3.3
          3.5  Biogen                                                3.4
          3.6  Bio-Technology General                                3.5
          3.7  British Bio-technology Limited                        3.6
          3.8  California Biotechnology                              3.7
          3.9  Centocor                                              3.8
          3.10  Celltech Limited                                     3.10
          3.11  Cetus                                                3.10
          3.12  Chiron                                               3.12
          3.13  Ciba-Geigy                                           3.13
          3.14  Collaborative Research                               3.13
          3.15  Damon Biotech                                        3.14
          3.16  Genentech                                            3.16
          3.17  Genetics Institute                                   3.17
          3.18  Genzyme                                              3.19
          3.19  Immunex                                              3.20
          3.20  Innogenetics                                         3.21
          3.21  Johnson and Johnson                                  3.22
          3.22  Kabi                                                 3.22
          3.23  Eli Lilly                                            3.23
          3.24  MicroGeneSys                                         3.23
          3.25  Novo-Nordisk                                         3.24
          3.26  Repligen                                             3.25
          3.27  Roche                                                3.26
          3.28  Schering-Plough                                      3.27
          3.29  Transgene                                            3.28
          3.30  Transgenic Sciences                                  3.28
          3.31  Xoma                                                 3.29
          
        PART IV - TABLES AND APPENDICES
        
        TABLE  1:  Nucleic Acid Nomenclature                         4.1
        TABLE  2:  The Twenty Common Amino Acids                     4.2
        TABLE  3:  The Genetic Code                                  4.3
        TABLE  4:  Examples of Restriction Enzymes                   4.4
        TABLE  5:  Molecular Components of an E coli Cell            4.5
        TABLE  6:  Examples of Bacterial Operons                     4.5
        TABLE  7:  The Characteristics of Some Plasmids              4.6
        TABLE  8:  Normal Values for the Cellular Elements
                   in Human Blood                                    4.7
        TABLE  9:  The Human Immunoglobulins                         4.8
        TABLE 10:  Some Properties of Mouse Immunoglobulins          4.9
        TABLE 11:  Units of Mass and Length                          4.9
        TABLE 12:  Potential Methods of Interferon Production        4.10
        APPENDIX 1:    Enzymes Used in Gene Manipulation             4.11
        APPENDIX II:   Vectors Used in Recombinant DNA
                       Technology                                    4.14
        APPENDIX III:  Some Notes of Interest                        4.16
        APPENDIX IV:   BIOTECHNOLOGY PRODUCTS BY DEVELOPING
                       COMPANY                                       4.17
        APPENDIX V:    COMPANIES BY BIOTECHNOLOGY PRODUCT GROUP      4.25
        
        ACKNOWLEDGEMENTS                                             4.33

                                 F I G U R E S
        
        Fig  1:  The Primary Structure of DNA                        1.117
        Fig  2:  The Three-Dimensional Structure and Hydrogen
                 Bonding Details of Double-Stranded DNA              1.119
        Fig  3:  The Beta-Globin Gene Cluster                        1.120
        Fig  4:  DNA replication                                     1.121
        Fig  5:  Steps in the Formation of an Initiation
                 Complex with the 70S Bacterial Ribosome             1.122
        Fig  6:  Types of DNA Cleavage Produced by
                 Different Restriction Enzymes                       1.123
        Fig  7:  Restriction Enzyme Map of the Cloning
                 Vector, pAT153                                      1.124
        Fig  8:  The Cloning of DNA by the Homopolymer
                 Tailing Method                                      1.125
        Fig  9:  The Addition of Restriction Linkers to
                 Foreign DNA                                         1.126
        Fig 10:  Features of gt11                                    1.127
        Fig 11:  The Structure of IgG                                1.128
        Fig 12:  Production of a Conventional Polyclonal
                 Antiserum in the Mouse                              1.129
        Fig 13:  Steps in the Production of Monoclonal
                 Antibodies                                          1.130
        Fig 14:  The Purification of Antigens using
                 Monoclonal Antibodies Covalently Linked
                 to an Affinity Matrix                               1.131
        Fig 15:  The Chemical Structures of the Amino Acids          2.87
        Fig 16:  Animal Cell Vectors - General Purpose               2.88
        Fig 17:  Animal Cell Vectors - Expression                    2.89
        Fig 18:  The Structure of Chromatin                          2.90
        Fig 19:  The Process of Conjugation in E coli                2.91
        Fig 20:  Types of Crossover Event which Occur in
                 Genetic Recombination                               2.92
        Fig 21:  The Expression of a Typical Eukaryotic Gene         2.93
        Fig 22:  The Reading of codons in a Polynucleotide
                 Chain Showing the Effect of Frame-Shift
                 Mutations on the Reading Frame                      2.94
        Fig 23:  A Hairpin Loop (Gierer Loop)                        2.95
        Fig 24:  Steps in the Induction of
                 á-Galactosidase in E coli                           2.96
        Fig 25:  The Structure of the Bacterial lac Operon           2.97
        Fig 26:  The Chemical Structures of the
                 Components of Nucleic Acids                         2.98
        Fig 27:  Correspondence between the his Operon
                 Structure and the Biosynthetic Pathway
                 Leading to Histidine Synthesis                      2.99
        Fig 28:  The Structure of the Plasmid, pBR322                2.100
        Fig 29:  The Formation of Different Types of
                 Antigen:Antibody Complex                            2.101
        Fig 30:  The pUC Vector                                      2.102
        Fig 31:  Steps in the Repression of Histidinyl
                 Dehydrogenase                                       2.103
        Fig 32:  The Use of Restriction Enzymes to Produce
                 Recombinant DNA Molecules                           2.104
        Fig 33:  The Protein and RNA Components of Ribosomes         2.105
        Fig 34:  The Structure of a 70S Ribosome from E coli         2.106
        Fig 35:  The Structure of Transfer RNA                       2.107
        Fig 36:  The Base Sequence in a Yeast Alanine-tRNA           2.108
        Fig 37:  Yeast Vectors                                       2.109



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