The last decade has been marked by an unprecedented boom in the number and variety of technologies used to discover and develop new drugs; many of these technologies arose from work surrounding the human genome project. For example, gene sequencing, gene expression profiling and genotyping have greatly benefited from technological advances, resulting in dramatically higher throughputs and rapid declines in cost. For some other areas it has proven to be more of a challenge to achieve performance improvements of the same magnitude. Defining the function of each gene, or more specifically, the protein it encodes, has been particularly challenging. It is not yet possible to study gene function with the type of “massively parallel” approaches used in other fields.
 

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