Table of Contents
Emerging Drug Discovery Technologies
Executive Summary 10
Introduction 10
Lab-on-a-chip/microfluidics 11
Nanotechnology 12
RNA interference 13
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
iv
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
v
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
vi
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
vii
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
viii
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: Cepheid’s 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 Nanosphere’s 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
