1. Overview 4
1.1 Objectives 4
1.2 Scope 4
1.3 Methodology 6
1.4 Executive Summary 6
2. RNA Interference (RNAi) 9
2.1 Introduction 9
2.2 Overview of RNA Interference 9
2.2.1 Classes of Small RNAs: siRNA, rasiRNA and miRNA 10
2.2.2 Mechanism of RNAi In Vivo 11
2.3 Glossary 15
2.4 What Areas of Research Does RNAi Impact? 16
2.4.1 RNAi Technology in Life Sciences Research, Drug Discovery and Development 16
3. Technology Trends in RNAi Space 21
3.1 Overview 21
3.2 End-User Segmentation 21
3.3 Technologies for Inducing RNAi 22
3.3.1 Methods for Detecting Gene Silencing 23
3.3.2 Libraries of siRNAs/shRNAs to Knockdown Genes En Masse 24
3.3.2.1 Publicly Available Largescale Mammalian RNAi Libraries 25
3.3.2.2 The RNAi Consortium (TRC) 26
3.3.3 Comparison of Strategies for Target Validation 28
3.3.3.1 Market Shifts in RNAi Space: Where Is It Headed? 29
3.3.4 miRNA-Based RNAi: Leading Edge of RNAi Space 30
3.3.4.1 Biological Function of miRNAs 30
3.3.4.2 Role of miRNAs in Cancer 31
3.3.4.3 Role of miRNAs in Human Cancer 32
3.4 SWOT Analysis of Technologies and Vendors in RNAi Space 34
4. RNAi Market Analysis 37
4.1 Overview 37
4.2 Market Data Collection and Respondent Pool 37
4.2.1 Respondent Pool Characteristics 38
4.3 RNAi Technologies/Products in Research Applications 40
4.4 RNAi Technologies/Products: Market Shares (Quantitative) 40
4.5 Quantitative Metrics of RNAi Usage: Market Opportunity and Growth 43
4.5.1 Growth of Various Segments in RNAi Space 45
4.5.2 Product Formats and Representation in RNAi Marketplace 46
4.6 RNAi Marketplace: Challenges, Unmet Needs and Drivers 51
4.6.1 Unmet Needs in RNAi Space 52
4.6.2 RNAi Market: Qualitative Growth Drivers 54
5. The RNAi Landscape 55
5.1 Overview 55
5.2 Market Segmentation of RNAi and Segment Characteristics 55
5.3 Quantitative Market Opportunities in RNAi Space 57
5.3.1 Opportunities in miRNA Space 57
5.3.2 Opportunities in siRNA/shRNA Space 59
5.4 RNAi Product Offerings and Associated Business Models 61
6. Company Profiles 64
6.1 Actigenics 64
6.2 Alnylam Pharmaceuticals 65
6.3 Amaxa 65
6.4 Ambion 66
6.5 Asuragen 66
6.6 B-Bridge International 67
6.7 Benitec 67
6.8 Bio-Rad Laboratories 67
6.9 BioVentures 68
6.10 Cenix BioScience 68
6.11 Clontech 68
6.12 CytRx 69
6.13 Dharmacon 70
6.14 DNAVision 70
6.15 Exiqon 70
6.16 GeneCopoeia 71
6.17 GenoSensor 71
6.18 IDT 71
6.19 Invitrogen 72
6.20 InvivoGen 72
6.21 Isis Pharmaceuticals 73
6.22 Nucleonics 74
6.23 Open Biosystems 74
6.24 OriGene 75
6.25 Panomics 75
6.26 Promega 75
6.27 QIAGEN 75
6.28 Roche 78
6.29 RZPD 79
6.30 Sigma-Aldrich 79
6.31 Sima Therapeutics 80
6.32 System Biosciences 81
INDEX OF TABLES
Table 2.1: Advantages/Disadvantages of siRNAs & shRNAs as Inducers of RNAi in Mammalian Cells 16
Table 2.2: Suppliers of Enabling Technologies and Tools in RNAi Space 17
Table 2.3: Suppliers of siRNA/shRNA Products (by Product/Service Class) 19
Table 3.1: Currently Utilized Technologies for Inducing RNAi-Mediated Knockdown 23
Table 3.2: Comparison of mRNA Detection Technologies 23
Table 3.3: Characteristics of Various Mouse and Human RNAi Libraries Publicly Available 25
Table 3.4: Comparison of Formats for Library-Based Gene Knockdown 27
Table 3.5: Strategies for Target Validation by Pharma/Biotech: RNAi and Others 28
Table 3.6: SWOT Analysis of siRNA Oligonucleotides 34
Table 3.7: Transfection Reagents (Lipid-Mediated Delivery) 35
Table 3.8: shRNA Plasmid Constructs 35
Table 3.9: shRNA Pooled Libraries or Arrayed Collections (Retroviral/Lentiviral Delivery) 36
Table 5.1: RNAi Market Segmentation and Research Settings 55
Table 5.2: Segment 1: Basic Life Science Research Utilizing RNAi Tools and Technologies 55
Table 5.3: Segment 2: RNAi for Drug Discovery and Development 56
Table 5.4: Segment 3: RNAi Research for Development of RNAi Therapeutics 56
Table 5.5: Segment 4: RNAi Fee-for-Service Business 57
Table 5.6: Grants Awarded and Research Spending in miRNA Space, 2005-2007 57
Table 5.7: RNAi Opportunity and Market Size: Quantitative Model, 2006-2009 60
INDEX OF FIGURES
Figure 2.1: The miRNA Processing Pathway 12
Figure 2.2: Mechanisms of Small RNA-induced Gene Regulation 14
Figure 2.3: Growth of Scientific Publications Addressing miRNAs, 2001-2006 14
Figure 3.1: End-User Segmentation of RNAi Space 21
Figure 4.1: Geographical Breakdown of RNAi End-User Survey Respondents 38
Figure 4.2: Affiliation of RNAi End-User Survey Respondents 38
Figure 4.3: Utilization of RNAi Technologies/Products by Respondent Pool 39
Figure 4.4: RNAi Utilization Period: Breakdown of Respondent Pool 39
Figure 4.5: Research Applications Using RNAi Technologies/Products 40
Figure 4.6: Types of RNAi Technologies Currently Utilized 41
Figure 4.7: RNAi Technologies Most Commonly Utilized Currently by End-Users 41
Figure 4.8: Types of RNAi Technologies: Expected Use in Six to 18 Months 42
Figure 4.9: Evolution of Market Shares of RNAi-Inducing Technologies 43
Figure 4.10: Number of Experiments Involving RNAi Conducted Per Week 43
Figure 4.11: Range of Research Dollars Spent Monthly on RNAi Research 44
Figure 4.12: RNAi Experiment Throughput Correlated with Type of RNAi Technology Used 45
Figure 4.13: Growth/Decline Rate of RNAi Marketplace Segments (Six to 18 Months) 46
Figure 4.14: Product Formats Utilization for RNAi Research: Current and Six to 18 Months 47
Figure 4.15: Companies Offering Product Formats for Currently Used RNAi Products 49
Figure 4.16: RNAi Product Offerings/Formats Use: (Projections--Six to 18 Months) 50
Figure 4.17: Percentage Change of RNAi Product Offerings/Formats (Six to 18 Months) 51
Figure 4.18: Key Challenges Faced by End-Users in RNAi Space 52
Figure 4.19: Unmet Needs in RNAi Space Ranked by Importance to End-Users 53
Figure 5.1: Growth and Evolution of miRNA Space 58
Figure 5.2: Elements of RNAi Value Chain 59
Figure 5.3: Growth and Evolution of RNAi (siRNA/shRNA) Space 61
Figure 5.4: Market Revenues Based on Components of siRNA Experimental Paradigm 63