Animal Biotechnology - Technologies, Markets and Companies

0. Executive Summary ...... 12

1. Introduction to Animal Biotechnology .............. 14

Introduction......... 14

Historical evolution of animal biotechnology .............. 14

Basics of biotechnology........... 15

DNA .15

RNA.15

Genes................16

Single nucleotide polymorphisms ...............16

Gene expression ..16

Gene regulation ...17

Proteins ..............17

Functions of proteins .........18

Monoclonal antibodies.............18

Animal genetics .... 19

Molecular genetics19

Twinning in cattle.19

Pig genetics.........19

Genetic studies in dogs ...........19

Animal genomics... 20

The mouse genome ................20

The dog genome ..20

The cat genome ...22

Marsupial genomes.................22

Genomes of non-human primates ..............22

Chimpanzee genome .........22

Genome of the rhesus macaque............23

Livestock genomics ................23

Bovine genome .................24

Bovine SNP map ...............24

Pig genome ....25

Horse genomics ................25

Sheep genome26

Chicken genome ..26

Priority genome list of the National Human Genome Research Institute.................27

Applications of animal genomics.................27

Genomics of disease resistance.............28

Statistical genomics to improve breeding .................28

Animal proteomics  28

Applications of proteomics in animals .........29

Caseins in goat milk ..........29

Lactic acid bacteria............29

Applications of proteomics in animal healthcare ........30

Bioinformatics...... 30

Application of nanobiotechnology for animal health ... 31

Recombinant protein manufacture............ 31

Animal biotechnology in relation to other technologies ................ 32

2. Application of Biotechnology in Animals........... 34

Introduction......... 34

Genetic engineering ................ 34

Livestock improvement by genetic engineering ..............34

Disease control by genetic engineering .......34

Limitations and precautions for genetic engineering........35

Transgenic animal technology. 35

Cloning animals ...36

Nuclear transfer technology36

Nuclear bisection for cloning .................38

Zona-free cloning method ..38

Abnormalities in cloned animals ............39

Cloning from embyonic cells .................40

Cloning of rabbits ..............40

Cloning the rat41

Cloning the horse ..............41

Cloning the cow ................41

Cloning the dog.................42

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Cloning in primates ...........42

Retrovector-mediated production of transgenic animals ..42

Episomal vector-mediated gene delivery .....43

Sperm-mediated gene transfer 43

Lentiviral transduction of male germ-line stem cells .......44

Lentiviral transgenesis ............45

Transgenic pharmaceuticals.... 45

Proteins from the milk of transgenic animals .................45

Advantages of milk as source of transgenic proteins .......46

Therapeutic proteins from rabbit milk ....47

Recombinant human antibodies from cows ...............48

Therapeutic proteins from goat milk ......48

Chicken transgenesis for the production of biopharmaceuticals ..........49

Concluding remarks about production of recombinant proteins in animals .............49

Companies involved in production of transgenic pharmaceuticals .......49

Transgenic food products........ 50

Milking genetically modified cows ...............50

Transgenic fish ....50

Cloned animals as sources of milk and meat51

Animal feeds from transgenic plants......... 51

Transgenic modification of plants to increase nutritional value of animal feeds.......52

Transgenic disease models ..... 52

Technologies to create transgenic disease models ..........52

Gene manipulation techniques ..............52

Embryonic stem cells for gene targeting.53

Homologous recombination 53

Animal models of human diseases .........54

Transgenic models for studying human drug metabolism and toxicity .54

The Human Genome Project and the role of transgenics..55

Genomic and proteomic analyses of transgenic animal models...........55

Concern about health and welfare of transgenic animals .56

Safety of transgenic technology .................56

Concluding remarks about use of transgenic animals ......57

RNA interference technology .. 57

RNAi versus antisense ............57

Applications of RNAi in animal biotechnology .................57

Xenotransplantation ............... 58

Pigs for xenotransplantation ....58

Genetically engineered pigs for transplants...............59

Risks of xenotransplantation.................59

World Health Organization and xenotransplantation........60

Companies involved in xenotransplantation .60

Ethical aspects of animal biotechnology.... 61

3. A Biotechnology Perspective of Animals Diseases .............. 62

Introduction......... 62

Infections in animals .............. 62

Viral infections.....63

Avian influenza .................63

Animal surveillance of influenza ............65

Animal corona viruses and human SARS 66

Avian coronavirus..............66

Canine parvovirus .............67

Classical swine fever..........67

Developing new treatments against FMDV ................67

Equine infectious anemia....68

Foot-and-mouth disease ....69

Porcine reproductive and respiratory syndrome virus .70

Rinderpest......71

Bacterial infections .................71

Bovine tuberculosis ...........71

Mycoplasmal pneumonia .........71

Protozoal infections ................72

Neosporosis....72

Toxoplasmosis 72

Coccidiosis .....72

Nematodes..........73

Infections that cross the species barrier ......73

Complications of bacterial infections and antibiotic use in animals ......73

Transmissible spongiform encephalopathies (TSEs) ... 74

Scrapie ...............74

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Bovine spongiform encephalopathy ............74

Epidemiology of BSE..........75

Human health implications of BSE .........76

Breeding animals protected against BSE 76

TSE research .......76

Prion gene haplotyping ......76

Pharmacological approaches to TSE research............77

Molecular diagnostic approach to TSE research .........77

RNAi for knockdown of the bovine prion gene ...........77

Chronic wasting disease.......... 78

Chronic wasting disease in wildlife .........78

Chronic wasting disease of the cattle in Sudan..........79

Chronic wasting in dairy cows in the Netherlands ......79

Genetic disorders in farm animals............. 80

Diseases of pet animals .......... 80

Canine Anemia.....80

Heart failure in dogs ...............81

Cancer in cats and dogs ..........81

Cancer clinical trials in dogs81

Canine Comparative Oncology Genomics Consortium.82

Preventive veterinary medicine ................ 82

Prevention of introduction of foreign animal diseases......83

Producing transgenic cattle resistant to BSE 83

Zoonotic diseases.. 83

Collaborative management of animal and human health .84

4. Molecular Diagnostics in Animals ... 86

Introduction......... 86

Nucleic acid technologies........ 86

The polymerase chain reaction.86

Basic Principles of PCR .......86

Target selection ................87

Detection of amplified DNA.87

Real-time PCR systems ......87

LightCycler PCR system......88

Molecular beacons.............88

Applications of PCR in veterinary medicine ...............88

Fluorescent in situ hybridization .................89

Immunodiagnostics ................ 91

Enzyme-linked immunoassays .91

Bovine Gamma Interferon Test 91

Antigen diagnosis of trichinosis 92

Parachek™ for the diagnosis of Johne's disease .............92

Antibodies for differentiation between vaccinated and infected animals .................93

Biochip/microarray technology................. 93

Applications of microarrays in animal biotechnology .......94

Cattlearray3800 for functional genomics 94

eSensor™ electrochemical biochip .........95

Biosensors ............ 95

Immunosensors ...96

Biosensor for ovulation prediction in dairy cows ........96

Flow cytometry for animal diagnostics...... 97

Molecular imaging in animals.. 97

Applications of molecular diagnostics in animals ........ 98

Canine DNA testing ................98

Diagnostic aids to selective breeding ..........98

Selection of desirable traits 98

Using genetic markers for improved milk production in dairy cattle99

Application of bovine genomics for improving milk yield ...............99

Recognition of hereditary syndromes ... 100

Genetic markers in animals ... 100

SNP genotyping in animals ................. 100

SNP genotyping for selective breeding of chicken .... 101

Animal identity and parentage analysis ..... 101

Animal species identification in food ......... 102

Diagnosis of infections .......... 102

Bacterial infections .......... 102

Diagnosis of viral infections ................ 102

Molecular diagnosis of avian influenza.. 104

Diagnosis of parasitic infections .......... 105

Detection of natural or bioterror threats to livestock  106

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Molecular diagnosis of prion diseases........ 106

Bovine spongiform encephalopathy...... 106

Testing for BSE in living animals ......... 108

Prions in urine ................ 108

Diagnosis of chronic wasting disease in wildlife ....... 109

Developing new tests for prion diseases.... 109

Differentiation among various types of TSEs ........... 109

Protein cyclic amplification ................. 109

Antibody tests for prion diseases......... 110

Scrapie genotyping.......... 110

A real-time ultrasonic method for prion protein detection ........... 111

Companies involved in developing molecular diagnostics for TSEs .... 111

Diagnosis of genetic disorders 112

Genetic screening of companion animals ................ 112

Preimplantation genetic diagnosis........ 112

Diagnosis of cancer in animals ................. 112

Diagnosis of food-borne pathogens......... 113

Introduction ...... 113

Molecular diagnostic methods used in food-borne infections ............ 113

Limitations of use of molecular probes in food analysis . 114

Companies with technologies for food pathogen detection ............... 114

Detection of chemicals in foods of animal origin ....... 115

5. Biotechnology-based Veterinary Medicine ...... 118

Introduction....... 118

Biotechnology versus pharmaceutical products ........ 118

Role of biotechnology in drug discovery and development.......... 119

Cost of veterinary vs. human drug discovery and development ........ 119

Advantages and disadvantages of testing biotech products in animal models ....... 120

Biotechnolgoy-based antiparasitic drugs.... 120

Non-antibiotic strategies for control of infections in animals...... 120

Probiotics .......... 121

Potential role for probiotics in the human gut.......... 121

Potential role for probiotics in animals.. 121

Probiotic bacteria for control of pathogens in cattle.. 121

Nonantibiotic drugs for infections in animals ................ 122

Immunomodulation as an alternative to antibiotics in infections .. 123

Cathelicidins: effector molecules of mammalian innate immunity  123

Bacteriophage therapy for antibiotic resistance ....... 123

Biotechnology for treating tendon injuries................ 124

Use of growth factors to facilitate tendon injuries ......... 124

Productivity enhancers ......... 124

Bovine somatotropin for increasing milk production in dairy cows..... 125

Use of growth factors............ 126

Transgenic plant products for use in animals............ 126

Biotechnology-based vaccines ................ 126

Modern vaccines without viral non-structural proteins... 127

Vaccines for tick control ........ 127

Plant-derived vaccines for use in animals .. 127

Genetically engineered vaccines............... 128

Application of nucleic acid vaccines in veterinary medicine ......... 129

DNA vaccines 129

Genetic engineering of live rabies vaccines ............. 130

DNA vaccine for tuberculosis............... 131

Potential for genetically engineered vaccines for Johne's disease. 131

DNA vaccines for West Nile encephalitis ................. 131

Genetically engineered vaccines for equine encephalitis ............. 132

Vaccines against avian influenza ......... 133

Vaccines against parasitic infections .... 134

Recombinant marker vaccines ................. 134

Marker vaccines for foot-and-mouth disease........... 134

Marker vaccine for Newcastle disease .. 135

Vaccines for classical swine fever ........ 135

Using RNAi to develop vaccines for viral infections in prawns ...... 136

Nano-bead vaccine adjuvant.. 136

Companies developing biotechnology-based vaccines ... 136

Biotechnology in treatment of parasitic infections .... 137

Biotechnology in the treatment of CNS injuries in pet animals.... 137

Paraplegia due to acute spinal cord injury in dogs ........ 137

RNAi for suppression prions in livestock . 138

Cell Therapy........ 138

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Umbilical cord blood stem cells ................ 139

Application of stem cells in veterinary medicine ........... 139

Use of stem cells to repair tendon injuries in horses  139

Stem cells for spinal cord injury in dogs ................. 140

Gene therapy ...... 140

Gene therapy vectors ...... 140

Gene therapy by mitochondrial transfer ................. 141

In utero gene therapy...... 141

Applications of gene therapy in veterinary medicine ..... 142

Gene therapy for mucopolysaccharidosis VII in dogs 142

Gene therapy to increase disease resistance........... 142

Gene therapy for infections ................ 143

Gene therapy for hematological disorders............... 143

Gene therapy for endocrine disorders .. 144

Gene therapy for arthritis. 144

Cancer gene therapy ............ 144

Brain tumors in cats and dogs............. 144

Breast cancer in dogs ...... 145

Canine hemangiosarcoma  146

Canine melanoma ........... 146

Canine soft tissue sarcoma................. 147

Melanoma in horses......... 147

6. Research in Animal Biotechnology 148

Introduction....... 148

Research institutes ............... 148