RNA Interference Markets

Since its discovery, the naturally occurring RNA (ribonucleic acid) interference effect has been acclaimed as the most exciting technical breakthrough in biological research in the last decade. Some industry analysts predict that RNA interference (RNAi) may even surpass PCR as a top technology. RNAi allows scientists to silence the expression or effect of a gene under study. This is known as gene knockdown. This field has rapidly emerged as a fast-growing new market. The purpose of this TriMark Publications report is to review the market for RNAi testing equipment and supplies. RNAi is a mechanism in molecular biology where the presence of certain fragments of double-stranded RNA (dsRNA) interferes with the expression of a particular gene which shares a similar sequence with the dsRNA. This study defines the dollar volume of sales, both worldwide and in the U.S., and analyzes the factors that influence market size and growth for RNAi testing. The main objectives of this study are to: 1) understand the different sectors of RNAi testing market and to look at a description of the instruments, reagents and supplies marketed by major companies in each segment; 2) obtain a complete understanding of the individual RNAi-testing platforms—from basic principles to clinical applications; 3) discover feasible market opportunities by identifying high-growth applications in different analytical diagnostic areas, with a focus on the biggest and expanding markets; 4) focus on global industry developments and trends through an in-depth analysis of the major world markets for RNAi measurement technology, including growth forecasts; and 5) present market figures related to the current value of RNAi testing, market projections, market share, key players and sector growth rates.
[Fade out the market survey infos]

1 Overview 7

1.1 Objectives 7

1.2 Scope 7

1.3 Methodology 9

1.4 Executive Summary 10



2 RNA Interference (RNAi) 13

2.1 Introduction 13

2.2 Overview of RNA Interference 13

2.2.1 Classes of Endogenous Small RNAs: siRNA, rasiRNA and miRNA 14

2.2.2 Mechanism of RNAi In Vivo 15

2.3 Glossary 18

2.4 What Areas of Research Does RNAi Impact? 19

2.4.1 RNAi Technology in Life Sciences Research, Drug Discovery and Development
20

2.4.2 RNAi Technology in Agriculture 26



3 Technology Trends in RNAi Space 29

3.1 Overview 29

3.2 End-User Segmentation 29

3.3 Technologies for Inducing RNAi 30

3.3.1 Methods for Detecting Gene Silencing 31

3.3.2 Comparison of Strategies for Target Validation 32

3.3.3 Libraries of siRNAs/shRNAs to Knock Down Genes En Masse 32

3.4 miRNA-Based RNAi: The Leading Edge of RNAi Space 38

3.4.1 Biological Function of miRNAs 39

3.4.2 Role of miRNAs in Disease 40

3.4.3 miRNA-based Diagnostics 44

3.4.4 miRNA-based Therapeutics 46

3.5 Market Shifts in RNAi Space: Where Is It Headed? 47

3.5.1 Intellectual Property and Patent Issues 48

3.5.2 Patents Covering the Molecular Characteristics of the RNAi Agent 48

3.5.3 Funding in RNAi Space: Grants, Venture Capital and IPOs 50

3.5.4 Partnerships, Alliances, Mergers and Acquisitions 51

3.6 SWOT Analysis of Technologies and Vendors in RNAi Space 53



4 RNAi Market Analysis 56

4.1 Overview 56

4.2 Market Data Collection and Respondent Pool 56

4.2.1 Respondent Pool Characteristics 56

4.3 RNAi Technologies / Products in Research Applications 58

4.4 RNAi Technologies/Products: Market Shares (Quantitative) 59

4.5 Quantitative Metrics of RNAi Usage: Market Opportunity and Growth 62

4.5.1 Growth of Various Segments in RNAi Space 64

4.5.2 Product Formats and Representation in RNAi Marketplace 65

4.6 RNAi Marketplace: Challenges, Unmet Needs and Drivers 71

4.6.1 Unmet Needs in RNAi Space 72

4.6.2 RNAi Market: Qualitative Growth Drivers 74



5 The RNAi Landscape 75

5.1 Overview 75

5.2 Market Segmentation of RNAi and Segment Characteristics 75

5.3 Quantitative Market Opportunities in RNAi Space 77

5.3.1 Opportunities in miRNA Space 77

5.3.2 Opportunities in siRNA/shRNA Space 79

5.4 RNAi Product Offerings and Associated Business Models 80

5.5 Challenges for RNAi Therapeutic Development 82



6 RNAi-Based Therapeutics: The Emerging Industry Landscape 84

6.1 Factors Contributing to the Success of RNAi Therapeutics 84

6.2 Advantages and Disadvantages of siRNA-based Drugs 85

6.3 Opportunities and Challenges with RNAi-based Therapeutics 85

6.4 The Gene Therapy Precedent 86

6.5 The Antisense Precedent 87

6.6 Interferon Response 87

6.7 Delivery of RNAi-based Therapeutics 88

6.8 Off-Target Effects 90

6.9 Overwhelming the Endogenous RNAi System—Affecting the microRNA Pathway 90

6.10 RNAi-based Therapeutics 90

6.10.1 Cancer 91

6.10.2 Cardiac Disease 93

6.10.3 Immunologic Disease 94

6.10.4 Infectious Disease 94

6.10.5 Inflammation 97

6.10.6 Lifestyle Therapeutics 97

6.10.7 Metabolic Disease 97

6.10.8 Neurologic Disease 98

6.10.9 Ophthalmic Disease 98

6.10.10 Renal Disease 100

6.10.11 Respiratory Disease 100



7 Company Profiles—U.S. 101

7.1 Alfacell Corporation 102

7.2 Allele Biotechnology and Pharmaceuticals, Inc. 102

7.3 Alnylam Pharmaceuticals 102

7.4 Ambion 104

7.5 Asuragen, Inc. 105

7.6 Avalon Pharmaceuticals, Inc. 105

7.7 B-Bridge International, Inc. 106

7.8 Bio-Rad Laboratories 106

7.9 Calando Pharmaceuticals, Inc. 107

7.10 Cepheid 107

7.11 Cequent 107

7.12 Clontech Laboratories, Inc. 108

7.13 CombiMatrix Corporation 108

7.14 Cyntellect, Inc. 108

7.15 CytRx Corp. 109

7.16 Dharmacon 110

7.17 Dicerna 110

7.18 Galenea Corporation 110

7.19 GeneCopoeia, Inc. 111

7.20 GeneThera, Inc. 111

7.21 Genlantis 111

7.22 GenoSensor 111

7.23 GRL, Inc. 112

7.24 IDT 112

7.25 Imgenex Corporation 112

7.26 Ingenuity Systems 113

7.27 Intradigm Corporation 113

7.28 Invitrogen 113

7.29 InvivoGen 114

7.30 Isis Pharmaceuticals, LLC 114

7.31 LC Sciences 115

7.32 Lentigen Corporation 116

7.33 Merck & Co., Inc. 116

7.34 Mirus Bio Corporation (Acquired by Roche) 116

7.35 Monsanto 116

7.36 Nastech Pharmaceutical Company, Inc. 117

7.37 New England BioLabs 118

7.38 Nucleonics, Inc. 118

7.39 Open Biosystems, Inc. 119

7.40 OPKO Health, Inc. 119

7.41 OriGene 120

7.42 Panomics, Inc. 120

7.43 PhaseRx 120

7.44 Promega Corp. 120

7.45 Quark Pharmaceuticals, Inc. 121

7.46 RXi Pharmaceuticals Corporation 121

7.47 Senetek PLC 122

7.48 Sigma-Aldrich 122

7.49 Sirna Therapeutics 123

7.50 Sirnaomics, Inc. 124

7.51 SomaGenics, Inc. 125

7.52 System Biosciences 125

7.53 Tacere Therapeutics 125

7.54 Targeted Genetics Corporation 126

7.55 Third Wave Technologies 126

7.56 Traversa 126



8 Company Profiles—Europe 128

8.1 Actigenics SA 128

8.2 Amaxa 128

8.3 AstraZeneca PLC 129

8.4 Cenix Bioscience GmbH 129

8.5 deVGen N.V. 130

8.6 DNAVision 130

8.7 Exiqon 131

8.8 Genovis 131

8.9 genOway 131

8.10 imaGenes GmbH 132

8.11 MWG Biotech AG 132

8.12 OZ Biosciences 132

8.13 Prosensa Holding 133

8.14 QIAGEN 133

8.15 RNAx GmbH (Germany) 134

8.16 Roche 135

8.17 Rosetta Genomics, Ltd. 136

8.18 Santaris Pharma A/S 136

8.19 Silence Therapeutics PLC 137

8.20 TaconicArtemis GmbH 138

8.21 TRANSAT 138



9 Company Profiles—Asia-Pacific 140

9.1 alphaGEN Co., Ltd. 140

9.2 Benitec, Ltd. 140

9.3 Bioneer 140

9.4 CytoPathfinder, Inc. 141

9.5 Genesis Research & Development Corp. 141

9.6 GeneDesign, Inc. 142

9.7 GNI Pharmaceutical Corporation 142

9.8 Koken Co., Ltd. 142

9.9 NanoCarrier Co., Ltd. 142

9.10 Oncolys Biopharma, Inc. 143

9.11 RealGene Bio-Technologies, Inc. 143

9.12 Samchully Pharmaceuticals 143

9.13 Samyang Corp. 143

9.14 Shanghai Biochip 144

9.15 Shanghai GenePharma Co. 144

9.16 Shanghai Genomics, Inc. 144

9.17 Transgene Biotek, Ltd. 145

10 Company Profiles—Rest of the World 146

10.1 Benitec, Ltd. 146

10.2 Tekmira 147

[Fade out table of contents]

Table 2.1: Advantages/Disadvantages of siRNAs and shRNAs as Inducers of RNAi in
Mammalian Cells 20

Table 2.2: Prevalence of siRNA-mediated RNAi in Disease Models, as Reported in
Scientific Literature 22

Table 2.3: RNAi-based Therapeutics in Clinical Trials 23

Table 2.4: Suppliers of Enabling Technologies and Tools in RNAi Space 24

Table 2.5: Suppliers of siRNA/shRNA Products (by Product/Service Class) 25

Table 3.1: Currently-Utilized Technologies for Inducing RNAi-Mediated Knockdown
31

Table 3.2: Comparison of mRNA Detection Technologies 31

Table 3.3: Strategies for Target Validation by Pharma/Biotech: RNAi and Others
32

Table 3.4: Comparison of Formats for Library-Based Gene Knockdown 34

Table 3.5: Characteristics of Various Publicly-Available Mouse and Human RNAi
Libraries 35

Table 3.6: Disease-Related miRNAs 44

Table 3.7: Publicly-Available Computational Programs for Identifying miRNA
Sequences/Targets 45

Table 3.8: Seminal Patents in RNAi 49

Table 3.9: Venture Capital Raised by Selected Companies in the RNAi Space 51

Table 3.10: List of Public Biotech Companies in RNAi Space 51

Table 3.11: SWOT Analysis of siRNA Oligonucleotides 53

Table 3.12: Transfection Reagents (Lipid-Mediated Delivery) 54

Table 3.13: shRNA Plasmid Constructs 54

Table 3.14: shRNA Pooled Libraries or Arrayed Collections (Retroviral/Lentiviral
Delivery) 55

Table 5.1: RNAi Market Segmentation and Research Settings 75

Table 5.2: Segment 1: Basic Life Science Research Utilizing RNAi Tools and
Technologies 75

Table 5.3: Segment 2: RNAi for Drug Discovery and Development 76

Table 5.4: Segment 3: RNAi Research for Development of RNAi Therapeutics 76

Table 5.5: Segment 4: RNAi Fee-for-Service Business 77

Table 5.6: Grants Awarded and Research Spending in miRNA Space, 2005 to 2008 77

Table 5.7: RNAi Opportunity and Market Size: Quantitative Model, 2006 to 2009 79

Table 5.8: Challenges for RNAi Therapeutic Development 82

Table 5.9: Technology Platforms used in RNAi Research 83

Table 6.1 : Similarities Between Antisense Oligonucleotides and siRNAs 87

Table 6.2: Disadvantages of siRNA Versus Antisense Oligonucleotides 87

Table 6.3: Delivery Vectors for siRNA and Hairpin-Encoding DNA for In Vivo
Experiments. 88

Table 6.4: Delivery Systems for siRNA and Hairpin-Encoding DNA for In Vivo
Experiments. 89

Table 6.5: Delivery Systems for RNAi-based Therapeutics 89

Table 6.6: Diseases for RNAi Therapeutics 90

Table 6.7: RNAi-Based Therapeutics Pipeline—Broken Out by Disease/Therapeutic
Area 91

Table 6.8: RNAi-Based Therapeutics Pipeline—Broken Out by Stage of Development
91

Table 6.9: Most Common Types of Cancer 92

Table 6.10: RNAi Therapeutics for Cancer in Phase I 92

Table 6.11: RNAi Therapeutics for Cancer in IND 93

Table 6.12: RNAi Therapeutics for Cardiac Disease in IND 93

Table 6.13: RNAi Therapeutics for Cardiac Disease in Pre-clinical/Research 94

Table 6.14: RNAi Therapeutics for Immunologic Disease in Pre-clinical / Research
94

Table 6.15: RNAi Therapeutics for Infectious Disease in Phase II 95

Table 6.16: RNAi Therapeutics for Infectious Disease in Phase I 95

Table 6.17: RNAi Therapeutics for Infectious Disease in IND 96

Table 6.18: RNAi Therapeutics for Infectious Disease in Pre-clinical/Research 96

Table 6.19: RNAi Therapeutics for Inflammatory Disease in Pre-clinical/Research
97

Table 6.20: RNAi Therapeutics for Life Style Therapies in IND 97

Table 6.21: RNAi Therapeutics for Metabolic Disease in Pre-clinical/Research 97

Table 6.22: RNAi Therapeutics for Neurologic Disease in Pre-clinical/Research 98

Table 6.23: RNAi Therapeutics for Ophthalmic Disease in Phase III 99

Table 6.24: RNAi Therapeutics for Ophthalmic Disease in Phase II 99

Table 6.25: RNAi Therapeutics for Ophthalmic Disease in Phase I 99

Table 6.26: RNAi Therapeutics for Ophthalmic Disease in Pre-clinical/Research 99

Table 6.27: RNAi Therapeutics for Renal Disease in Phase I 100

Table 6.28: RNAi Therapeutics for Respiratory Disease in Pre-clinical/Research
100

Table 10.1: Nucleonics Products and Programs Ongoing/Pipeline 118

Table 10.2: Quark’s Product Pipeline 121

Table 10.3: Santaris’ Product Pipeline 137

Table 10.4: Silence Therapeutics’ Product Pipeline 138


Figure 2.1: The miRNA Processing Pathway 16

Figure 2.2: Growth of Scientific Publications Addressing miRNAs, 2001 to 2008 17

Figure 2.3: Mechanisms of Small RNA-induced Gene Regulation 18

Figure 2.4: Types of RNAi Compounds 20

Figure 2.5: Breakdown of Scientific Publications Related to RNAi by Geographic
Region, 2007 to 2008 21

Figure 3.1: End-User Segmentation of RNAi Space 29

Figure 3.2: RNAi Patents Filed Globally, by Geographical Origin 50

Figure 3.3: Selected Deals in RNAi Space 52

Figure 4.1: Geographical Breakdown of RNAi End-User Survey Respondents 57

Figure 4.2: Affiliation of RNAi End-User Survey Respondents 57

Figure 4.3: Utilization of RNAi Technologies/Products by Respondent Pool 57

Figure 4.4: RNAi Utilization Period: Breakdown of Respondent Pool 58

Figure 4.5: Research Applications Using RNAi Technologies/Products 59

Figure 4.6: Types of RNAi Technologies Currently Utilized 60

Figure 4.7: RNAi Technologies Most Commonly Utilized Currently by End-Users 60

Figure 4.8: Types of RNAi Technologies: Expected Use in Six to 18 Months 61

Figure 4.9: Evolution of Market Shares of RNAi-Inducing Technologies 62

Figure 4.10: Number of Experiments Involving RNAi Conducted per Week 62

Figure 4.11: Range of Research Dollars Spent Monthly on RNAi Research 63

Figure 4.12: RNAi Experiment Throughput Correlated with Type of RNAi Technology
Used 64

Figure 4.13: Current RNAi Market Share by Segments 65

Figure 4.14: Growth/Decline Rate of RNAi Marketplace Segments (Six to 18 Months)
66

Figure 4.15: Product Formats Utilization for RNAi Research (Current and Six to
18 Months) 67

Figure 4.16: Companies Offering Product Formats for Currently-Used RNAi Products
69

Figure 4.17: RNAi Product Offerings/Formats Use (Projections—Six to 18 Months)
70

Figure 4.18: Percentage Change of RNAi Product Offerings/Formats (Six to 18
Months) 71

Figure 4.19: Key Challenges Faced by End-Users in RNAi Space 72

Figure 4.20: Unmet Needs in RNAi Space Ranked by Importance to End-Users 73

Figure 5.1: Growth and Evolution of miRNA Space 78

Figure 5.2: Elements of RNAi Value Chain 79

Figure 5.3: Growth and Evolution of RNAi (siRNA/shRNA) Space 80

Figure 5.4: Market Revenues Based on Components of siRNA Experimental Paradigm
82

[Fade out list of tables / figures]