Global Gene Therapy Market Analysis & Forecast to 2022

Table of Contents

1.0 Introduction 20
1.1 Executive Summary 20
1.2 About this Report 22
1.3 Key Questions Answered in this Report 22
2.0 Gene Therapy: The Basics 25
2.1 Gene Therapy Techniques 26
2.1.1 Gene Augmentation Therapy 26
2.1.2 Gene Inhibition Therapy 27
2.1.3 Suicide Gene Therapy 28
2.2 Gene Therapy Routes 29
2.2.1 Ex Vivo Gene Delivery Route 29
2.2.2 In vivo Gene Delivery Route 30
2.3 CRISPR: Latest Technology in Gene Therapy 31
2.4 Challenges Associated with Developing Gene Therapies 32
2.5 Disadvantages of Gene Therapy 32
2.5.1 Short-Lived Nature of Gene Therapy 32
2.5.2 Immune Response 32
2.5.3 Problems with Viral Vectors 32
2.5.4 Multigenic Disorders 33
2.5.5 Insertional Mutagenesis 33
2.6 Concept to Product Candidates and Products 33
3.0 Historic Overview of Gene Therapy 36
3.1 The Formative Years of Gene Therapy 36
3.2 The Productive Years of Gene Therapy 37
3.2.1 Gendicine 37
3.2.2 Oncorine 38
3.2.3 Rexin-G 38
3.2.4 Neovasculgen 38
3.2.5 Glybera 38
3.2.6 Imlygic 39
3.2.7 Strimvelis 39
3.2.8 Zalmoxis 39
4.0 Gene Therapy Phase III Product Candidates 42
4.1 CardioNovo (Generx) 43
4.2 Collategene 43
4.3 LentiGlobin 43
4.4 Lenti-D 44
4.5 VM-202 44
4.6 Invossa 44
4.7 GS010 45
4.8 ADA-Lentiviral Gene Therapy 45
5.0 Gene Therapy Phase II Product Candidates 47
5.1 hF-IX gene/Hemophilia B 48
5.2 NaGlu gene/San Fillipo B Syndrome 48
5.3 StarGen/Stargardt disease 48
5.4 UshStat/Usher Syndrome Type 1B 48
5.5 Retinostat/Wet AMD 49
5.6 Lenti-D/Childhood Cerebral ALD 49
5.7 LentiGlobin/Beta Thalassemia 49
5.8 SB-728/HIV/AIDS 49
5.9 CERE-110/Alzheimer’s disease 50
5.10 AATD/Alpha-1 Antitrypsin deficiency 50
5.11 RS1 gene/X-linked juvenile Retinoschisis (XLRS) 50
5.12 SPK-CHM/Choroideremia 51
5.13 SPK-FIX/Hemophilia B 51
5.14 AMG0001/Primary Lymphedema 51
5.15 AMG0001/Ischemic heart disease 51
5.16 WASp /Wiskott-Aldrich syndrome 52
5.17 X-linked CGD 52
5.18 GSK2696273/ADA gene 52
5.19 VM106/Chronic Granulomatous Disease 53
5.20 VY-AADC01/Parkinson’s disease 53
6.0 Commercialization, Cost and Warranty of Gene Therapies 55
6.1 Reasons for the Extortionate Price 56
6.1.1 High Cost of Manufacturing 56
6.1.2 High Cost of Delivery 56
6.1.3 Lack of Comparative Studies as Evidence for Reimbursement Scheme 56
6.1.4 Lack of Competition 56
6.1.5 Potential for Cure 57
6.2 Strategies to Make Gene Therapy Affordable 57
6.3 The Age of First-Ever Warranty for Gene Therapy 57
7.0 The Strength of Gene Therapy Industry 59
7.1 Development of Appropriate Gene Delivery Vehicles 60
7.2 CRISPR-Based Therapy 60
7.3 Early Clinical Gene Therapy Protocols 61
7.4 Worldwide Scenario of Gene Therapy Clinical Trials 62
7.4.1 Geographical Distribution of Gene Therapy Clinical Trials 64
7.4.2 Gene Therapy Clinical Trials by Country 65
7.4.3 Major Indications Addressed by Gene Therapy Clinical Trials 66
7.4.4 Gene Types Transferred 68
7.4.5 Status of Gene Therapy Clinical Trials 70
7.5 Big Pharma’s Bold Venturing into Gene Therapy 71
7.5.1 Novartis’ Deal with GenVec 71
7.5.2 Strategic Alliance between GlaxoSmithKline and Fondazione Telethon 72
7.5.3 Amgen’s Acquisition of BioVex 72
7.5.4 Chiesi’s Rights to uniQure’s Glybera 72
7.5.5 Bayer’s Collaboration with Dimension Therapeutics 73
7.5.6 Genzyme’s (Sanofi) Collaboration with University of Florida 73
7.5.7 Pfizer’s Collaboration with Spark Therapeutics 73
7.5.8 Biogen Idec’s Collaboration with AGCT 73
7.5.9 Sanofi’s Tie-Up with Voyager Therapeutics 74
7.5.10 Bristol Myers Squibb’s Investment in uniQure 74
7.5.11 Joint Venture between Bayer and CRISPR Therapeutics AG 74
7.5.12 Flow of Funds to Gene Therapy Companies 74
7.6 Venture Investments by Body Systems 75
8.0 Vectors for Gene Delivery 78
8.1 Non-Viral Vectors 78
8.1.1 Inorganic Particles 79
8.1.1.1 Poly(lactic-co-glycolic acid) (PLGA) and poly lactic acid (PLA) 79
8.1.1.2 Chitosan 79
8.1.1.3 Poly(ethylene imine) (PEI) 79
8.1.1.4 Dendrimers 79
8.1.1.5 Polymethacrylates 80
8.1.2 Synthetic/Natural Biodegradable Particles 80
8.1.2.1 Cationic Liposomes 80
8.1.2.2 Lipid Nanoemulsions 80
8.1.2.3 Solid Lipid Nanoparticles (SLN) 80
8.1.2.4 Poly-L-Lysine 81
8.1.3 Physical Methods 81
8.1.3.1 Needle Injection 81
8.1.3.2 Gene Gun 81
8.1.3.3 Electroporation 81
8.1.3.4 Sonoporation 82
8.1.3.5 Photoporation 82
8.1.3.6 Magnetofection 82
8.1.3.7 Hydroporation 82
8.2 Viral Vectors for Gene Therapy 83
8.2.1 Key Properties of Viral Vectors 84
8.2.2 Best-Suited Viral Vectors for Gene Therapy 84
8.2.3 Potential Barriers for the Use of Viral Vectors 84
8.2.4 Types of Viral Vectors 85
8.2.4.1 Adenovirus Vectors 85
8.2.4.2 Retrovirus Vectors 86
8.2.4.3 Adeno-Associated Virus (AAV) 88
8.2.4.4 Lentivirus Vectors 90
8.2.4.5 Vaccinia Virus 91
8.2.5 Clinical Translation of Viral Vectors 92
8.2.6 Viral Vectors used in Clinical Trials 93
8.2.7 Culture Systems for Viral Vector Production 97
9.0 Clinical Applications of Gene Therapy 100
9.1 Leber Congenital Amaurosis (LCA) 101
9.1.1 Frequency 101
9.1.2 Genetic Basis of Leber Congenital Amaurosis 101
9.1.3 Pattern of Inheritance 101
9.1.4 Gene Therapy for LCA 101
9.2 Stargardt Macular Degeneration (SMD) 102
9.2.1 Frequency of SMD 102
9.2.2 Genetic Basis of SMD 102
9.2.3 Pattern of Inheritance 102
9.2.4 Gene Therapy 103
9.3 Choroideremia 103
9.3.1 Frequency 103
9.3.2 Genetic Basis of Choroideremia 103
9.3.3 Pattern of Inheritance 103
9.3.4 Gene Therapy 104
9.4 Leber Hereditary Optic Neuropathy (LHON) 104
9.4.1 Frequency of LHON 104
9.4.2 Genetic Basis of LHON 104
9.4.3 Pattern of Inheritance 104
9.4.4 Gene Therapy 104
9.5 Parkinson Disease 106
9.5.1 Frequency of Parkinson Disease106
9.5.2 Genetic Basis of Parkinson Disease 106
9.5.3 Inheritance of Parkinson Disease 107
9.5.4 Current Treatment for Parkinson Disease 107
9.5.5 Gene Therapy for Parkinson Disease 108
9.6 Spinal Muscle Atrophy 109
9.6.1 Genetic Basis 109
9.6.2 Pattern of Inheritance 109
9.6.3 Gene Therapy 109
9.7 Alzheimer Disease 110
9.7.1 Frequency 110
9.7.2 Genetic Basis 110
9.7.3 Pattern of Inheritance 110
9.7.4 Gene Therapy 110
9.8 Cystic Fibrosis 111
9.8.1 Genetic Basis 111
9.8.2 Inheritance of CF 111
9.8.3 Frequency of CF 111
9.8.4 Currently Available Treatments for CF 112
9.8.5 Gene Therapy for Cystic Fibrosis 113
9.9.1 Frequency 114
9.9.2 Genetic Basis 114
9.9.3 Pattern of Inheritance 114
9.9.4 Currently Available Treatments 115
9.9.5 Gene Therapy 115
9.10 X-Linked Adrenoleukodystrophy 115
9.10.1 Frequency 115
9.10.2 Genetic Basis 115
9.10.3 Pattern of Inheritance 116
9.10.4 Gene Therapy 116
9.11 Pompe Disease 116
9.11.1 Frequency 116
9.11.2 Genetic Basis 117
9.11.3 Pattern of Inheritance 117
9.11.4 Gene Therapy 117
9.12 Batten Disease (CLN3 Disease) 118
9.12.1 Frequency of Batten Disease 118
9.12.2 Genetic Basis of Batten Disease 118
9.12.3 Pattern of Inheritance 119
9.12.4 Gene Therapy for Batten Disease 119
9.13 Metachromatic Leukodystrophy 119
9.13.1 Frequency 120
9.13.2 Genetic Basis 120
9.13.3 Pattern of Inheritance 120
9.13.4 Gene Therapy 120
9.14 Sanfilippo Syndrome 120
9.14.1 Frequency 121
9.14.2 Genetic Basis 121
9.14.3 Patern of Inheritance 121
9.14.4 Gene Therapy 121
9.15 Hunter Syndrome 122
9.15.1 Genetic Basis 122
9.15.2 Pattern of Inheritance 122
9.15.3 Gene Therapy 123
9.16 Adenosine Deaminase Severe Combined Immunodeficiency (ADA-SCID) 123
9.16.1 Frequency 123
9.16.2 Genetic Basis 123
9.16.3 Pattern of Inheritance 123
9.16.4 Gene Therapy 124
9.17 X-Linked SCID 124
9.17.1 Frequency 124
9.17.2 Genetic Basis 124
9.17.3 Pattern of Inheritance 124
9.17.4 Gene Therapy 125
9.18 Chronic Granulomatous Disease (CGD) 126
9.18.1 Prevalence of CGD 126
9.18.3 Pattern of Inheritance 127
9.18.4 Current Treatments for CGD 127
9.18.5 Gene Therapy for CGD 127
9.19 Wischott Aldrich syndrome (WAS) 128
9.19.1 Frequency 128
9.19.2 Genetic Basis 128
9.19.3 Pattern of Inheritance 128
9.20 Hemophilia 129
9.20.1 Frequency of Hemophilia 130
9.20.2 Genetic Basis 130
9.20.3 Inheritance of Hemophilia 130
9.20.4 Currently Available Treatments for Hemophilia 130
9.20.5 Gene Therapy for Hemophilia 131
9.21 Sickle Cell Anemia 132
9.21.1 Frequency of Sickle Cell Anemia 133
9.21.2 Genetic Basis of Sickle Cell Anemia 133
9.21.3 Inheritance of Sickle Cell Anemia 133
9.21.4 Current Treatment for Sickle Cell Anemia 133
9.21.5 Gene Therapy for Sickle Cell Anemia 134
9.22 Beta Thalassemia 135
9.22.1 Frequency 135
9.22.2 Genetic Basis 135
9.22.3 Pattern of Inheritance 135
9.22.4 Gene Therapy 135
9.23.1 Frequency 136
9.23.2 Genetic Basis 136
9.23.4 Gene Therapy 136
9.25 Limb Girdle Muscle Dystrophy 2C/2D 138
9.25.1 Frequency 139
9.25.2 Genetic Basis 139
9.25.3 Pattern of Inheritance 139
9.25.4 Gene Therapy 140
9.26 Duchenne and Becker Muscular Dystrophy 140
9.26.1 Frequency 140
9.26.2 Genetic Basis 140
9.26.3 Pattern of Inheritance 140
9.27 Human Immunodeficiency Virus (HIV) 141
9.27.1 Currently Available Treatments 141
9.28 Epidermolysis Bullosa 143
9.28.1 Frequency 143
9.28.2 Genetic Basis 143
9.28.3 Pattern of Inheritance 144
9.28.4 Gene Therapy 144
9.29 Leukemia 144
9.29.1 Currently Available Treatments 144
9.29.2 Genetic Basis of Leukemia 145
9.29.3 Gene Therapy Strategies for Leukemia 146
9.30 Ovarian Cancer 146
9.30.1 Frequency of Ovarian Cancer 147
9.30.2 Genetic Basis of Ovarian Cancer 147
9.30.3 Currently Available Treatments for Ovarian Cancer 147
9.30.4 Gene Therapy for Ovarian Cancer 148
9.31 Pancreatic Cancer 149
9.31.1 Frequency of Pancreatic Cancer 149
9.31.2 Currently Available Treatments for Pancreatic Cancer 149
9.31.3 Genetic Basis 150
9.31.4 Gene Therapy for Pancreatic Cancer 151
9.32 Head and Neck Cancers 151
9.32.1 Frequency of Head and Neck Cancers 152
9.32.2 Currently Available Treatments for Head and Neck Cancers 152
9.32.3 Gene Therapy for Head and Neck Cancers 153
9.33 Melanoma 154
9.33.1 Frequency of Melanoma 154
9.33.2 Genetic Basis of Melanoma 154
9.33.3 Pattern of Inheritance 155
9.33.4 Available Treatments for Melanoma 155
9.33.5 Gene Therapy for Melanoma 156
9.34 Prostate Cancer 157
9.34.1 Frequency of Prostate Cancer 157
9.34.2 Genetic Basis of Prostate Cancer 157
9.34.3 Pattern of Inheritance 158
9.34.4 Currently Available Treatments for Prostate Cancer 158
9.34.5 Gene Therapy for Prostate Cancer 158
9.35 Breast Cancer 159
9.35.1 Frequency of Breast Cancer 159
9.35.2 Genetic Basis of Breast Cancer 159
9.35.3 Pattern of Inheritance 160
9.35.4 Currently Available Treatments for Breast Cancer 160
9.35.5 Gene Therapy 161
9.36 Fabry Disease 162
9.36.1 Frequency of Fabry Disease 162
9.36.2 Genetic Basis of Fabry Disease 162
9.36.3 Pattern of Inheritance 163
9.36.4 Currently Available Treatments for Fabry Disease 163
9.36.5 Gene Therapy for Fabry Disease 163
9.37 Hypercholesterolemia 164
9.37.1 Frequency of Hypercholesterolemia 164
9.37.2 Genetic Basis of Hypercholesterolemia 164
9.37.3 Current Medications for Hypercholesterolemia 165
9.37.4 Gene Therapy for Familial Hypercholesterolemia 165
9.38 Huntington Disease 166
9.38.1 Frequency of Huntington Disease 166
9.38.2 Genetic Basis of Huntington Disease 166
9.38.3 Inheritance of Huntington Disease 167
9.38.4 Current Treatment for Huntington Disease 167
9.38.5 Gene Therapy for Huntington Disease 168
9.39 Tay-Sachs Disease 168
9.39.1 Frequency of Tay-Sachs Disease 168
9.39.2 Genetic Basis of Tay-Sachs Disease 168
9.39.3 Pattern of Inheritance 169
9.39.4 Currently Available Treatments 169
9.39.5 Gene Therapy for Tay-Sachs Disease 169
10.0 Market Analysis 171
10.1 Global Market for Gene Therapy by Market Segment 175
10.2 Global Gene Therapy Market by Geography 176
10.3 Commercialization of Gene Therapy in China 177
10.4 Commercialization of Gene Therapy in the Philippines 178
10.5 Commercialization of Gene Therapy in Russia 178
10.6 Commercialization of Gene Therapy in Europe 178
10.6.1 Gene Therapy in France 180
10.6.2 Gene Therapy Landscape in U.K. 180
10.6.3 Gene Therapy Efforts in Germany 180
10.6.4 Australia’s Participation in Gene Therapy 180
10.6.5 New Regulatory Framework in Japan 181
10.7 Gene Therapy in the U.S. 181
10.7.1 Likely FDA Approval for Leukemia Treatment 181
10.8 Commercialization of Gene Therapy in South Korea 182
10.9 Additional Addresseable Markets for Gene Therapy 182
10.10 Challenges for Existing and Prospective Players 183
10.10.1 Challenges in Valuation 183
10.10.2 Challenges in Reimbursement 184
10.10.3 Challenges in Commercialization 185
10.11 Future Outlook for Gene Therapy 185
10.12 Potential Market for Gene Therapy Product Candidates 186
10.12.1 CardioNovo (Generx) 186
10.12.2 Collategene 186
10.12.3 Lentiglobin BB305 187
10.12.4 VM-202 187
10.12.5 Invossa 187
10.12.5 GS010 187
10.12.7 ADA Lentivirus 188
10.12.8 Lenti-D 188
11.0 Manufacturing of Viral Vectors and Logistics 190
11.1 Major Manufacturing Companies of Viral Vectors 190
11.2 Major Diseases Targeted by AAV Vectors in Clinical Trials 191
11.3 Major Companies Developing Lentiviral Vectors 192
11.4 Manufacturing Process 193
11.5 Contract Manufacturing 194
11.6 Targeted Delivery of Therapeutic Genes 195
11.7 Logistics Strategies for Gene Therapies 195
11.7.1 Threat to Gene Therapeutics during Transit 195
11.7.2 Impact of Varying Environmental Events on Cell and Gene Therapy Products 196
11.7.3 Pharmaceutical Cold Chain Logistics 196
11.6.4 Clinical Logistics 197
11.7 Cost of Clinical Trials for Biopharmaceuticals including Gene Therapy 198
11.7.1 Clinical Trial Expenditure by Disease 199
12.0 Company Profiles 203
12.1 4d Molecular Therapeutics LLC 203
12.1.1 AAV Vectors 203
12.1.2 4D’s Partnership with Pfizer 203
12.1.3 4D’s Partnership with uniQure 203
12.1.4 4D’s Partnership with Roche 204
12.1.5 4D’s Partnership with AGTC 204
12.1.6 4D’s Partnership with Benitec 204
12.1.7 4D’s Product Pipeline 204
12.2 Abeona Therapeutics LLC 205
12.2.1 Abeona’s Clinical Trial Programs 205
12.2.1.1 ABO-102 Phase I/II Clinical Trial 205
12.2.1.2 ABO-101 Phase I/II Clinical Trial 206
12.3 Advanced Cell & Gene Therapy LLC 206
12.3.1 Consulting Services 206
12.4 Advantagene Inc. 207
12.4.1 Gene Mediated Cytotoxic Immunotherapy (GMCI) 207
12.5 Adverum Biotechnologies Inc. 208
12.6 Addgene Inc. 209
12.6.1 Viral Service 209
12.7 Agilis Biotherapeutics LLC 209
12.7.1 Agilis Engineered DNA Therapeutics 210
12.7.2 DNA Therapeutics for AADC Deficiency 210
12.7.3 DNA Therapeutics for Friedreich’s ataxia (FA) 210
12.7.4 DNA Therapeutics for Angelman’s Syndrome 211
12.8 Angionetics Inc. 211
12.8.1 Technology 211
12.8.2 Generx Therapeutic Positioning 212
12.8.3 Product Pipeline 212
12.8.4 Addresseable Market 213
12.9 Applied Genetic Technologies Corporation (AGTC) 213
12.9.1 AGTC’s Technology 214
12.10 AnGes MG Inc. 215
12.10.1 HGF Plasmid 215
12.10.2 NF-kB Dekoy Oligonucleotide 216
12.10.3 DNA Therapeutic Vaccines 216
12.10.4 AnGes’ Alliance Partners 216
12.11 Asklepios BioPharmaceutical Inc. 217
12.11.1 Asklepios’ Collaborators 218
12.12 Audentes Therapeutics Inc. 219
12.12.1 Audentes’ Technology 219
12.13 AveXis Inc. 220
12.13.1 AVXS-101 220
12.14 AvroBio Inc. 221
12.14.1 Lentiviral Vectors for Rare Diseases 221
12.14.2 Cytokine IL-12 for Cancer Immunotherapy 221
12.14.3 Gene Vector 221
12.14.4 AvroBio’s Programs 222
12.15 Benitec Biopharma 222
12.15.1 ddRNAi Technology 222
12.15.2 Benitec’s In-House Programs 223
12.15.3 Benitecs Licensed Programs 223
12.16 BioCancell Therapeutic Inc. 224
12.16.1 The H19 Gene 224
12.16.2 BC-819 224
12.16.3 BC-821 225
12.17 BioMarin Pharmaceutical Inc. 225
12.17.1 BMN 270 225
12.18 Bluebird bio Inc. 226
12.18.1 Bluebird’s Program Pipeline 226
12.18.2 Lenti-D 227
12.18.3 LentiGlobin 227
12.18.4 Bluebird’s Partnership with Celgene 227
12.18.5 Bluebird’s Partnership with FivePrime 228
12.18.6 Bluebird’s Partnership with Kite Pharma 228
12.18.7 Bluebird’s Partnership with ViroMed 228
12.19 Brammer Bio LLC 229
12.19.1 Cell Therapy Services 229
12.19.2 Ex Vivo Gene Therapy 229
12.19.3 Viral Vector Manufacturing 229
12.20 Cellectis S.A. 230
12.20.1 UCART19 230
12.20.2 UCART123 231
12.20.3 UCART38 & UCARTCS1 231
12.20.4 UCART22 231
12.21 Clontech Laboratories Inc. 231
12.22 Cobra Biologics Ltd. 232
12.22.1 DNA Services 232
12.22.2 Virus Services 233
12.22.3 Protein Services 233
12.22.4 Microbiota Services 233
12.22.5 Fill and Finish Services 234
12.23 Copernicus Therapeutics Inc. 234
12.23.1 Technology 235
12.23.2 Cystic Fibrosis (CF) Program 235
12.23.3 Retinitis Pigmentosa (RP) Program 235
12.23.4 Parkinson’s Disease (PD) Program 235
12.24 Dimension Therapeutics Inc. 236
12.24.1 Dimension’s Gene Therapy Programs 236
12.25.1 SB Therapeutics 237
12.26 Editas Medicine Inc. 238
12.26.1 CRISPR/Cas9 & TALENs 238
12.27 Fibrocell Sciences Inc. 239
12.27.1 Fibroblast’s Pipeline 239
12.27.2 FCX-007 239
12.27.3 FCX-013 240
12.28 Florida Biologix 240
12.28.1 Services 240
12.29 Freeline Therapeutics Ltd. 241
12.29.1 Freeline’s Platform 241
12.30 Genable Technologies Ltd. 241
12.30.1 RhoNova 242
12.31 Genethon 242
12.31.1 Product Pipeline 242
12.32 Genlantis 243
12.32.1 DNA Transfection 243
12.32.2 siRNA Transfection 244
12.32.3 Neuronal Transfection 244
12.32.4 Customer Services 244
12.32.5 Protein Delivery/Transfection 244
12.32.6 siRNA Generation Kits 245
12.32.7 siRNA Transfection 245
12.32.8 Dicer Enzyme Kits 245
12.33 GenSight Biologics S.A. 245
12.33.1 GS010 246
12.33.2 GS030 246
12.34.1 AdenoVerse Technology 247
12.34.2 Antigen Discovery 247
12.34.3 Cell Lines 248
12.34.4 GenVec’s Product Pipeline 248
12.34.4.1 GGF166 for Hearing Loss 248
12.34.4.2 GV2311 – RSV Vaccine 249
12.34.4.3 GV2207 – HSV-2 Immunotherapeutic 249
12.35 Ichor Medical Systems Inc. 249
12.35.1 Technology 250
12.36 Immune Design Corp. 250
12.36.2 GLASS 251
12.37 Immusoft Corp. 251
12.37.1 Gene Delivery Technology 252
12.37.2 Key Indications being Addressed 252
12.38 Inovio Pharmaceuticals Inc. 252
12.38.1 Inovio’s Technology 253
12.39 Intellia Therapeutics Inc. 254
12.39.1 CRISPR/CAS9 254
12.39.2 Intellia’s Programs 255
12.40 Juventa Therapeutics Inc. 256
12.40.1 Non-Viral Gene Therapy 256
12.40.2 JVS-100 256
12.41 Kite Pharma Inc. 257
12.41.1 Chimeric Antigen Receptor (CAR) 257
12.41.2 T cell Receptor (TCR) 257
12.41.3 Cancer Programs 257
12.41.4 Kite Pharma’s Partnership with National Cancer Institute (NCI) 258
12.41.5 Kite Pharma’s Partnership with The Netherlands Cancer Institute (NKI) 258
12.41.6 Kite Pharma’s Partnership with Adimab 258
12.41.7 Kite Pharma’s Collaboration with Alpine Immune Sciences (AIS) 258
12.41.8 Kite Pharma’s Collaboration with Amgen 259
12.41.9 Kite Pharma’s Partnership with Bluebird Bio 259
12.41.10 Kite Pharma’s Partnership with Cell Design Labs 259
12.41.11 Kite Pharma’s Collaboration with Genentech 259
11.41.12 Kite Pharma’s Partnership with GE Global Research 259
12.41.13 Kite Pharma’s Partnership with Leiden University Medical Center 259
12.41.14 Kite Pharma’s Partnership with Leukemia & Lymphoma Society (LLS) 260
12.41.15 Kite Pharma’s Partnership with The Tel-Aviv Sourasky Medical Center 260
12.41.16 Kite Pharma’s Partnership with The UCLA David Geffen School of Medicine 260
12.42 Kolon Life Sciences Inc. 260
12.42.1 Invossa 261
12.42.2 KLS-1010 261
12.42.3 KLS-2020 261
12.42.4 KLS3020 261
12.43 Lentigen Technology Inc. 261
12.43.1 Lentiviral Vectors for Translational Research 262
12.43.2 Lenti-Viral Vector Technology 262
12.43.3 Clinical Trial Support 262
12.44 Lysogene S.A.S. 262
12.44.1 Lysogene’s rAAV Vectors 262
12.44.2 CNS Administration 263
12.44.3 MPS IIIA 263
12.44.4 GMI Gangliosidosis 263
12.44.5 Partnership with Alcyone Lifesciences Inc. 263
12.44.6 Partnership with University of Massachusetts 264
12.44.7 Partnership with Auburn University 264
12.44.8 Partnership with University of Manchester 264
12.45 Medgenics Inc. 264
12.45.1 Transduced Autologous Restorative Gene Therapy (TARGT) 264
12.46 Mirus Bio LLC 265
12.46.1 TransIT – Lenti Transfection Reagent 265
12.46.2 Ingenio Electroporation Kits 265
12.47 Mologen AG 266
12.47.1 Technologies 266
12.47.1.1 dSLIM 266
12.47.1.2 EnanDIM 266
12.47.1.3 MIDGE 266
12.47.2 Allogeneic Tumor Cell Bank 267
12.48 NanoCor Therapeutics Inc. 267
12.48.1 Biological Nanoparticle (BNP) Technology 268
12.48.2 Carfostin 268
12.49 Nature Technology Corp. (NTC) 268
12.49.1 Vector Cell Lines 268
12.49.2 DNA Manufacturing 269
12.49.3 Cloning & QC 269
12.49.4 Protein Products 269
12.49.5 Technology & Consulting 269
12.50 NightstaRx Ltd. 270
12.50.1 Project AAV2 REP1 270
12.51 Novasep Process SAS 270
12.51.1 Manufacturing Services for Customers 271
12.51.2 Contract Manufacturing Services 271
12.51.3 Purification Technologies 271
12.52 Omnia Biologics Inc. 272
12.52.1 Services 272
12.52.1.1 Preclinical and GMP Manufacturing 272
12.52.1.2 Process Development 272
12.52.1.3 Cell and Viral Banking 272
12.52.1.4 Aseptic Filling 272
12.53 ORCA Therapeutics B.V. 273
12.53.1 Technology 273
12.53.2 ORCA-010 273
12.53.3 Oncolytic Viruses Expressing p35 274
12.53.4 RNA Interference 274
12.54 OrphageniX 274
12.54.1 Technology 274
12.55 Oxford BioMedica plc 275
12.55.1 LentiVector Gene Delivery Technology 275
12.55.2 OXB-102 275
12.55.3 OXB-201 (RetinoStat) 276
12.55.4 CAR-T Cell Therapy 276
12.55.5 OXB-301 (TroVax) 276
12.55.6 SAR 422459 276
12.55.7 SAR421869 277
12.55.8 Partnership with Sanofi 277
12.55.9 Partnership with GlaxoSmithKline 277
12.55.10 Partnership with Novartis 277
12.55.11 Partnership with Immune Design Corp. 278
12.56 Oxford Genetics Ltd. 278
12.56.1 DNA Services 279
12.56.1.1 High Throughput Cloning Services 279
12.56.1.2 DNA Design and Protein Optimization Services 279
12.56.2 Cell Line Services 279
12.56.2.1 Cell Line Development 279
12.56.2.2 Custom Cell Engineering 279
12.56.3 Protein and Virus Services 280
12.56.3.1 Protein Expression and Antibody Engineering 280
12.56.3.2 Virus Construction and Production 280
12.56.4 Standard DNA Services 280
12.56.4.1 DNA Synthesis 280
12.56.4.2 Custom Cloning 281
12.56.4.3 Plasmid Preparation 281
12.57 REGENXBIO Inc. 281
12.57.1 NAV Technology 282
12.57.2 RGX-501 283
12.57.3 RGX-314 283
12.57.4 RGX-111 283
12.57.5 RGX-121 283
12.57.6 RGX-321 284
12.58 Renova Therapeutics Inc. 284
12.58.1 Renova’s Pipeline 284
12.59 RetroSense Therapeutics LLC 285
12.59.1 RST-001 285
12.60 Sangamo Biosciences Inc. 285
12.60.1 Sangamo’s Technology 286
12.60.2 Sangamo’s Product Pipeline 286
12.60.3 Sangamo’s Research Collaborations 287
12.61 Sarepta Therapeutics Inc. 288
12.61.1 RNA Medicine 288
12.61.2 RNA Modulation by PMO 288
12.61.3 Sarepta’s Programs for Duchenne Muscular Dystrophy (DMD) 289
12.61.4 Sarepta’s Programs for Infectious Diseases 290
12.62 Shanghai Sunway Biotech Co. Ltd. 290
12.62.1 Oncorine 291
12.63 SiBiono GeneTech Co. Ltd. 291
12.63.1 Gendicine 292
12.64 Sirion Biotech GmbH 292
12.64.1 Adenovirus 293
12.64.2 Lentivirus 293
12.64.4 Adeno-Associated Virus 293
12.64.5 AdenoBOOST & LentiBOOST 293
12.64.6 AdenONE 293
12.65 Spark Therapeutics Inc. 294
12.65.1 Spark Therapeutics’ Pipeline 294
12.66 Takara Bio Inc. 295
12.66.1 Takara’s Gene Therapy 295
12.66.1.1 Oncolytic Virus HF10 295
12.66.1.2 Engineered T-Cell Therapy (siTCR Gene Therapy) 295
12.66.1.3 CAR Gene Therapy 296
12.66.1.4 MazF Gene Therapy 296
12.67 Taxus Cardium Pharmaceutical Group Inc. 297
12.67.1 Generx 297
12.68 Tocagen Inc. 297
12.68.1 Technology 298
12.68.2 Toca 511 & Toca FC 298
12.69 ToolGen Inc. 299
12.69.1 Gene Editing 299
12.69.2 RNA-Guided Endonucleases (RGEN) 300
12.70 Transgene SA 300
12.70.1 TG4010 301
12.70.2 Pexa-Vec 301
12.70.3 TG6002 301
12.70.4 TG1050 302
12.70.5 TG4001 302
12.70.6 Immunotherapy against Tuberculosis 302
12.71 uniQure N.V. 302
12.71.1 Glybera 303
12.72 Vascular Biologics Ltd. 303
12.72.1 VBL’s Cancer Platform 304
12.73 Vical Inc. 305
12.73.1 Poloxamer Delivery System 305
12.73.2 ASP0113 306
12.73.3 HSV-2 Therapeutic Vaccine 306
12.73.4 CyMVectin Prophylactic CMV Vaccine 306
12.73.5 VL-2397 Antifungal 306
12.74 ViroMed Co., Ltd. 307
12.74.1 VM202 307
12.74.2 Fast Track Designation for VM202 307
12.74.3 VM501 308
12.75 Vivebiotech SL 308
12.75.1 GMP Solutions 308
12.75.2 Viral Vector Services 308
12.75.3 ZELIGEN Technology 309
12.76 Voyager Therapeutics Inc. 309
12.76.1 Product Pipeline 309
12.77 Xenon Pharmaceuticals Inc. 310
12.77.1 Glybera 310

List Of Figures

Figure 2.1: Shematic of Gene Therapy using a Virus Vector 25
Figure 2.2: Schematic to Explain Gene Augmentation Therapy 27

Figure 2.3: Schematic to Exlain Gene Inhibition Therapy 27
Figure 2.4: Schematic to Explain Suicide Gene Therapy 28
Figure 2.5: Ex vivo Route of Gene Delivery in Gene Therapy 29
Figure 2.6: In Vivo Route of Gene Delivery in Gene Therapy 30
Figure 7.1: Academic Mettle: Number of Research Papers Published, 1975-2016 59
Figure 7.2: Number of Gene Therapy Clinical Trials Approved Worldwide, 1989-2016 63
Figure 7.3: Geographical Distribution of Gene Therapy Clinical Trials, 2016 64
Figure 7.4: Major Countries Participating in Gene Therapy Clinical Trials, 2016 66
Figure 7.5: Major Indications Addressed by Gene Therapy Clinical Trials, 2016 67
Figure 7.6: Top Gene Types Transferred 69
Figure 7.7: Phases of Gene Therapy Clinical Trials 70
Figure 7.8: Venture Investment in Gene Therapy by Body System as of 2014 76
Figure 8.1: Top Five Vectors used in Gene Therapy 97
Figure 9.1: Global Market for Cystic Fibrosis Therapeutics, 20162022 113
Figure 9.2: Global Market for Hemophilia Factor Proteins, 2016-2022 131
Figure 9.3: Global Market for Sickle Cell Anemia, 2016-2022 134
Figure 9.4: Global Market for HIV Therapeutics, 2016-2022 142
Figure 9.5: Global Market for Leukemia Drugs, 2016-2022 145
Figure 9.6: Global Market for Ovarian Cancer Therapeutics, 2016-2022 148
Figure 9.7: Global Market for Pancreatc Cancer Therapeutics, 2016-2022 150
Figure 9.8: Global Market for Head & Neck Cancer Therapeutics, 2016-2022 153
Figure 9.9: Global Market for Melanoma Therapeutics, 2016-2022 156
Figure 9.10: Global Market for Prostate Therapeutics, 2016-2022 158
Figure 9.11: Global Market for Breast Cancer Therapeutics, 2016-2022 161
Figure 9.12: Global Market for Cholesterol Lowering Drugs, 2016-2022 165
Figure 9.13: U.S. Market for HD Therapeutics, 2016-2022 167
Figure 10.1: Global Market for Gene Therapy Technologies, Services and Products, 2016-2022 173
Figure 10.2: Market for Technologies, Services and Products by indication, 2016-2022 174
Figure 10.3: Percent Share of Gene Therapy Market by Indication, 2016 174
Figure 10.4: Global Market for Gene Therapy by Market Segment, 2016-2022 175
Figure 10.5: Percent Share of Gene Therapy market by Geography, 2016 177
Figure 11.1: Major Ten Companies Developing AAV Vector Candidates 190
Figure 11.2: Diseases and Corresponding Number of Drugs Studied using AAV Vectors 191
Figure 11.3: Major Ten Companies Developing Lentiviral Vector Candidates 192
Figure 11.4: Overview of a Typical Viral Vector Manufacturing Process 193
Figure 11.5: Global Cold Chain and Non-Cold Chain Logistics Spending, 2016-2022 197
Figure 11.6: Global Spending on Logistics Related to Clinical Trials, 2016-2022 197
Figure 11.7: Estimated Average Per-Patient Clinical Trial Costs by Phase of Study 199
Figure 11.8: Estimated Per-Patient Clinical Trial Expenditure by Indication 200

INDEX OF TABLES

Table 2.1: Differences between Somatic Gene Therapy and Germline Gene Therapy 26
Table 2.2: Few Examples of Suicide Gene Products 28
Table 2.3: Genetic Diseases Treatable by Ex Vivo Gene Therapyusing Bone Marrow Cells 30
Table 2.4: Examples of Diseases Treatable by In Vitro Route of Gene Delivery 31
Table 2.5: Important Gene Therapy Players and Product Candidates 34
Table 3.1: Approved Gene Therapy Products 40
Table 4.1: Number of Non-Cancer Phase III Gene Therapy Candidates as of 2016 42
Table 5.1: Key Players with Phase II Product Candidates 47
Table 6.1: Commercialization Status of Gene Therapies in E.U. Member Countries 55
Table 6.2: Prices for Gene Therapy 56
Table 7.1: Approved and Published Clinical Gene Therapy Protocols 61
Table 7.2: Number of Gene Therapy Clinical Trials Approved Worldwide, 1989-2016 62
Table 7.3: Geographical Distribution of Gene Therapy Clinical Trials, 2016 64
Table 7.4: Gene Therapy Clinical Trials by Country, 2016 65
Table 7.5: Gene Therapy Clinical Trials by Indications, 2016 67
Table 7.6: Gene Types Transferred in Gene Therapy Clinical Trials 69
Table 7.7: Phases of Gene Therapy Clinical Trials 70
Table 7.8: Timeline of Big Pharma Investment and Licensing in Gene Therapy, 2010-2016 71
Table 7.9: Funds Raised by Gene Therapy Companies Since 2013 75
Table 8.1: Most Utilized Non-Viral Vectors in Gene Therapy 78
Table 8.2: Advantages and Disadvantages of Four Physical Methods in Gene Delivery 82
Table 8.3: Major Types of Viral Vectors used in Gene Therapy, Advantages and Disadvantages 83
Table 8.4: Key Properties of Viral Vectors 84
Table 8.5: Advantages and Disadvantages of Viral Vectors by Type 85
Table 8.6: Salient Features of Adenovirus Vectors 85
Table 8.7: Advantages and Disadvantages of Adenovirus Vectors 86
Table 8.8: Salient Features of Retrovirus 86
Table 8.9: Advantages and Disadvantages of Retroviral Vectors 87
Table 8.10: Comparison of Retrovirus and Adenovirus 87
Table 8.11: Salient Features of Adeno-Associated Virus Vectors 88
Table 8.12: Advantages and Disadvantages of Adeno-Associated Vectors 89
Table 8.13: AAV Serotypes 89
Table 8.14: Genes Transduced by AAV for Specific Diseases 90
Table 8.15: Salent Features of Lentivirus Vectors 91
Table 8.16: Advantages and Disadvantages of Lentiviral Vectors 91
Table 8.18: Advantages and Disadvantages of Pox/Vaccinia Vectors 92
Table 8.19: Major Features of Viral Vectors by Type 93
Table 8.20: Examples of Clinical Trials Using Retroviruses & Lentiviruses 94
Table 8.21: Examples of Clinical Trials Using Retroviruses & Lentiviruses 95
Table 8.22: Vectors Used in Gene Therapy Clinical Trials, 2016 96
Table 8.23: Examples of Virus Vector Manufacturing Systems 98
Table 9.1: Clinical Applications of Gene Therapy 100
Table 9.2: Identifying Number, Intervention and Status of Gene Therapy Trials for Blindness 105
Table 9.3: Gene Therapy Clinical Trial for Eye Disorders 105
Table 9.4: Genes and Loci Underlying Parkinson Disease 107
Table 9.5: Gene Therapy Clinical Trials for Parkinson Disease 108
Table 9.6: U.S. Data on Cystic Fibrosis, 2000-2015 112
Table 9.7: Gene Therapy Clinical Trials for Cystic Fibrosis 113
Table 9.8: Gene Therapy Clinical Trials for Pompe Disease 117
Table 9.9: Gene Therapy Clinical Trials for Batten Disease 119
Table 9.10: Gene Therapy Clinical Trials for Immune Disorders 126
Table 9.12: Gene Therapy Clinical Trials for Wiskott-Aldrich Syndrome 129
Table 9.13: Gene Therapy Clinical Trials for Hemophilia 131
Table 9.14: Gene Therapy Product Candidates for Hemophilia A and B 132
Table 9.15: Ongoing Gene Therapy Clinical Trials for Sickle Cell, Fanconi and Thalassemia 137
Table 9.16: Gene Therapy Clinical Trials for Heart Diseases 138
Table 9.17: Gene Therapy for Muscular Dystrophies 141
Table 9.18: Gene Therapy Clinical Trials for HIV 143
Table 9.19: Gene Therapy Clinical Trials for Blood Cancer 146
Table 9.20: Gene Therapy Clinical Trials for Ovarian Cancer 148
Table 9.21: Gene Therapy Clinical Trials for Pancreatic Cancer 151
Table 9.22: Gene Therapy Clinical Trials for Head and Neck Cancers 153
Table 9.23: Gene Therapy Clinical Therapy for Melanoma 156
Table 9.24: Gene Therapy Clinical for Prostate Cancer 159
Table 9.25: Gene Therapy Clinical Trials for Breast Cancer 162
Table 9.26: Gene Therapy Clinical Trials for Fabry Disease 163
Table 9.27: Gene Therapy for Familial Hypercholesterolemia 166
Table 9.28: Gene Therapy Clinical Trials for Tay-Sachs disease 169
Table 10.1: Estimated Market for Five Gene Therapy Products in the U.S. in the Next 20 Years 172
Table 10.2: Market for Technologies, Services and Products by Indication, 2016-2022 173
Table 10.3: Global Market for Gene Therapy by Market Segment, 2016-2022 175
Table 10.4: Percent Share of Gene Therapy market by Geography, 2016 176
Table 10.5: The Estimated Drug Market that is Wide Open for Gene Therapy Product Candidates Focusing on 13 Diseases 183
Table 11.1: Major Ten Companies Developing AAV Vectors 190
Table 11.2: Diseases and Corresponding Number of Drugs Studied using AAV Vectors 191
Table 11.3: Major Ten Companies Developing Lentiviral Vector Candidates 192
Table 11.4: Global Cold Chain and Non-Cold Chain Logistics Spending, 2016-2022 196
Table 11.5: Estimated Average Per-Patient Clinical Trial Costs by Phase of Study 198
Table 11.6: Estimated Per-Patient Clinical Trial Expenditure by Indication 200
Table 11.7: Patient-Per Clinical Trial Expenditure by Disease Area and Phase 201
Table 12.1: 4D’s Product Pipeline 205
Table 12.2: Abeona’s Product Pipeline 206
Table 12.3: Advantagene’s Program Overview 207
Table 12.4: Adverum’s Pipeline of Gene Therapy Programs 208
Table 12.5: Agilis DNA Therapeutic Programs 210
Table 12.6: Generx Product Pipeline 212
Table 12.7: Potential Economic Opportunity for Generx (Ad5FGF-4) 213
Table 12.8: AGTC’s Ophthalmology Development Programs 214
Table 12.9: AnGes’ Product Pipeline 215
Table 12.10: Asklepios’ Product Pipeline 218
Table 12.11: Audentes’ Pipeline 220
Table 12.12: AvroBio’s Programs 222
Table 12.13: Benitec’s In-House Programs 223
Table 12.14: Benitecs Licensed Programs 223
Table 12.15: Bluebird’s Program Pipeline 227
Table 12.16: Product Pipeline from Cellectis 230
Table 12.17: Dimension’s Product Pipeline 236
Table 12.18: Fibroblast’s Product Pipeline 239
Table 12.19: Genethon’s Pipeline 243
Table 12.20: Summary of GenVec’s Product Pipeline 248
Table 12.21: Immune Design’s Product Pipeline 250
Table 12.22: Inovio’s Pipeline of Products 253
Table 12.23: Types of Genome Editing 255
Table 12.24: Intellia’s Product Pipeline 255
Table 12.25: Kite’s Product Pipeline 258
Table 12.26: Lysogene’s Product Pipeline 263
Table 12.27: Medgenics’ Product Pipeline 265
Table 12.28: Mologen’s Product Pipeline 267
Table 12.29: Oxford BioMedica’s Product Pipeline 278
Table 12.30: REGENXBIO’s Therapeutic Programs 282
Table 12.31: Renova’s Pipeline 284
Table 12.32: Sangamo’s Product Pipeline 287
Table 12.33: Sarepta’s Product Pipeline for DMD 289
Table 12.34: Sarepta’s Programs for Infectious Diseases 290
Table 12.35: Spark Therapeutics’ Pipeline 294
Table 12.36: Tocagen’s Product Pipeline 298
Table 12.37: Transgene’s Product Pipeline 300
Table 12.38: unQure’s Pipeline 303
Table 12.39: VBL’s Cancer Pipeline 304
Table 12.40: Vical’s Product Pipeline 305
Table 12.41: Voyager Therapeutics, Product Pipeline 309