Emerging Drug Discovery Technologies: Building competitive advantage through lab-on-a-chip, nanotechnology and RNAi

Table of Contents

Chapter 1 Introduction 16

• Summary 16
• Overview 17
• A historical overview of the drug discovery process 18
• Drug discovery in the 1950s and 1960s 18
• Drug discovery in the 1980s 19
• Drug discovery today 20
• Emerging drug discovery technologies 22
• Lab-on-a-chip/microfluidic technologies 22
• Nanotechnology 23
• RNA interference 24
• Report objectives 25

Chapter 2 Lab-on-a-chip/microfluidics 27

• Summary 27
• Introduction 28
• LOC technologies 31
• LOC design issues 32
• Microarrays 32
  • Spotted microarrays 33
  • In situ fabricated arrays 34
• DNA applications 35
• Protein applications 36
• The LabChip 37
• Lab-on-a-CD 41
• Chip-based electrospray system for mass spectroscopy 43
• HPLC-on-a-chip 44
• Microfluidic PCR 45
• Multiplexed capillary electrophoresis 48
• Market drivers and restraints 48
• Market drivers 49
  • HTS 49
  • Reduction of human error 50
  • Reduced exposure to hazardous materials 50
  • Reduction in sample requirement and routine tasks 50
  • Cost savings 51
• Market restraints 51
  • Reduction in demand 51
  • Reluctance to replace old systems with new technologies 52
• Market analysis 52
• Competitive structure 54
• Market share 54
• Aclara BioSciences 55
• Advion BioSciences, Inc. 56
• Agilent Technologies 57
• BioMicro Systems 58
• BioTrove Inc. 59
• Caliper Life Sciences 60
• Cepheid 62
• CombiMatrix Corp. 63
• Eksigent Technologies 64
• Epigem Limited 65
• Fluidigm Corp. 66
• Gyros AB 67
• Nanogen 68
• Nanostream Inc. 70
• Protiveris 71
• Sequenom 71
• Zyomyx 72
• Future developments 73

Chapter 3 Nanotechnology 77

• Summary 77
• Introduction 78
• Nanotechnologies 79
• Applications 81
  • Drug discovery and drug delivery 81
  • Biosensing 82
  • Other applications 82
• Public opinion 82
• Funding 83
• Market 84
• Nano-enabled drug discovery tools 84
• Atomic force microscopy 85
• Nano-mass spectroscopy 86
• Dip-pen nanolithography 87
• Nanoarrays 88
• Nanoparticles for drug discovery 90
• Quantum dots and gold nanoparticles 92
• Nanoshells 95
• Nanobarcode particles 97
• Nano-enabled drugs 98
• Abraxane 98
• RenaZorb 98
• Antimicrobial emulsions 99
• Antioxidants and fullerenes 99
• Industry challenges 101
• High demands of drug discovery applications 102
• Long-term stability of nanomaterials 103
• Technical issues in nano-assembly and molecular manufacturing 104
• Barriers to collaborations 104
• Lack of test standardization 104
• Scalability 105
• Pharmaceutical companies reluctant to invest in nanotechnology 105
• Funding for nanotechnology 105
• Market drivers and restraints 106
• Market drivers 108
  • Technological drivers 108
  • Increased funding 109
  • Social and economic factors 110
• Market restraints 111
  • Uncertainty 111
  • Public awareness 111
  • Environmental concerns 112
  • Detection of incurable diseases 112
• Large expectations 112
• Market analysis 113
• Competitive structure 114
• Market share 115
• 3DM Inc. 117
• Alnis Biosciences Inc. 118
• American Pharmaceuticals Partners Inc. 119
• BioCrystal Ltd. 120
• BioForce NanoSciences Inc. 120
• CrystalPlex Corp. 122
• C Sixty Inc. 122
• Evident Technologies, Inc. 123
• NanBio Corp. 124
• Nanosphere 125
• PharmaSeq, Inc 126
• Quantum Dot Corp. 128
• Future developments 129

Chapter 4 RNA interference (RNAi) 133

• Summary 133
• Introduction 134
• Gene silencing 137
• Methods for gene silencing 137
  • Aptamers 138
  • Ribozymes 138
  • Peptide nucleic acid (PNA) and PNA-DNA chimeras 140
  • Antisense oligonucleotides 140
  • RNA interference (RNAi) 142
• RNAi mechanism 142
• RNAi approaches 143
• siRNA 144
• ddRNAi 144
• MicroRNAs (miRNAs) 145
• Short hairpin RNAs (shRNAs) 146
• Delivery methods 146
• Delivery using chemical transfections 147
• Delivery using electroporation 149
• Delivery using expression vectors 149
• Delivery using cell-penetrating peptides 151
• In vivo delivery of siRNAs 151
• Industry challenges 152
• Intellectual property issues 153
• Off-target effects 153
• Delivery of siRNA in vitro and in vivo 154
• Toxicity issues from RNAi 154
• Pricing issues 155
• Efficacy of RNAi 155
• Standardization of technologies 156
• Proof of therapeutic potential 156
• Market drivers and restraints 157
• Market drivers 158
  • Demand for accelerated drug discovery 158
  • Resolution of intellectual property issues 158
  • Robust, efficient and potent technology 158
  • Functional genomics and proteomics studies 159
  • Vector-based and siRNA price decline 159
  • Reliability 159
• Market restraints 160
  • Expensive RNAi reagents 160
  • Delivery of siRNA 160
  • Failure of antisense drugs 160
  • Lack of robust clinical data 161
  • Selection and design of appropriate siRNA 161
  • Toxicity and off-target effects 161
• Market analysis 161
• Revenue forecasts 161
• Trends by geographic region 163
  • North America 164
  • Europe 164
  • Japan 164
  • Rest of the World 164
• Competitive structure 165
• Market share analysis 166
• Ambion 168
• Alnylam Pharmaceuticals, Inc. 168
• Benitec Ltd 169
• CytRx Corp. 170
• Cenix BioScience 170
• Devgen 171
• Dharmacon, Inc. 172
• Eurogentec (EGT) 173
• Imgenex Corp. 173
• Immusol Inc. 174
• Invitrogen Corp. 174
• InvivoGen 174
• MWG Biotech 175
• Proligo 175
• Promega 176
• Qiagen. 176
• Sirna Therapeutics 177
• Future developments 178

Chapter 5 Appendix 181

• Research methodology and information sources 181
• Primary research methodology 181
• Secondary research methodology 182
• Market sizing 182
• Forecasting 182
• Index 184
• Abbreviations and acronyms 185

List of Figures

• Figure 1.1: Drug development process during the 1950s and 1960s 19
• Figure 1.2: Drug development process during the 1980s 20
• Figure 1.3: Drug development process today 21
• Figure 2.1: The Gyros Bioaffy lab-on-a-CD 42
• Figure 2.2: Advion BioSciences ESI Chip 44
• Figure 2.3: HPLC-on-a-chip 45
• Figure 2.4: Cepheids GeneXpert cartridges for PCR analysis 47
• Figure 2.5: Market drivers and restraints for LOC/microfluidics devices in drug discovery 49
• Figure 2.6: Microfluidics/LOC revenue forecasts, 2005-2012 53
• Figure 2.7: Microfluidics/lab-on-a-chip market shares, 2004 54
• Figure 3.1: Expression of cells using QDots 94
• Figure 3.2: Binding of Nanospheres nanoparticle probe to a selected genetic or proteomic target 95
• Figure 3.3: Nano-enabled drug discovery industry challenges 102
• Figure 3.4: Market drivers and restraints for nano-enabled drug discovery 107
• Figure 3.5: Nano-enabled drug discovery revenue forecasts, 2004-2012 114
• Figure 3.6: Nanoenabled drug discovery market shares, 2004 116
• Figure 4.7: RNAi pathways 143
• Figure 4.8: Industry challenges faced by RNAi industry participants 152
• Figure 4.9: Market drivers and restraints for RNAi technology 157
• Figure 4.10: RNAi revenue forecasts and growth rates, 2004-2012 162
• Figure 4.11: RNAi revenues by geographic region, 2004 163
• Figure 4.12 RNAi market shares, 2004 166

List of Tables

• Table 2.1: Microfluidics/LOC revenue forecasts, 2005-2012 53
• Table 3.2: Nano-enabled drug discovery revenue forecasts, 2004-2012 113
• Table 4.3: RNAi revenue forecasts, 2004-2012 162
• Table 5.4: Abbreviations and acronyms, A-L 185
• Table 5.5: Abbreviations and acronyms, M-Z 186