Reportlinker Adds RNAi - Technologies, Markets and Companies

Jun 03, 2010, 12:45 ET from Reportlinker

NEW YORK, June 3 /PRNewswire/ -- Reportlinker.com announces that a new market research report is available in its catalogue:

RNAi - technologies, markets and companies

http://www.reportlinker.com/p0203551/RNAi---technologies-markets-and-companies.html

Summary

RNA interference (RNAi) or gene silencing involves the use of double stranded RNA (dsRNA). Once inside the cell, this material is processed into short 21-23 nucleotide RNAs termed siRNAs that are used in a sequence-specific manner to recognize and destroy complementary RNA. The report compares RNAi with other antisense approaches using oligonucleotides, aptamers, ribozymes, peptide nucleic acid and locked nucleic acid.

Various RNAi technologies are described, along with design and methods of manufacture of siRNA reagents. These include chemical synthesis by in vitro transcription and use of plasmid or viral vectors. Other approaches to RNAi include DNA-directed RNAi (ddRNAi) that is used to produce dsRNA inside the cell, which is cleaved into siRNA by the action of Dicer, a specific type of RNAse III. MicroRNAs are derived by processing of short hairpins that can inhibit the mRNAs. Expressed interfering RNA (eiRNA) is used to express dsRNA intracellularly from DNA plasmids.

Delivery of therapeutics to the target tissues is an important consideration. siRNAs can be delivered to cells in culture by electroporation or by transfection using plasmid or viral vectors. In vivo delivery of siRNAs can be carried out by injection into tissues or blood vessels or use of synthetic and viral vectors.

Because of its ability to silence any gene once the sequence is known, RNAi has been adopted as the research tool to discriminate gene function. After the genome of an organism is sequenced, RNAi can be designed to target every gene in the genome and target for specific phenotypes. Several methods of gene expression analysis are available and there is still need for sensitive methods of detection of gene expression as a baseline and measurement after gene silencing. RNAi microarray has been devised and can be tailored to meet the needs for high throughput screens for identifying appropriate RNAi probes. RNAi is an important method for analyzing gene function and identifying new drug targets that uses double-stranded RNA to knock down or silence specific genes. With the advent of vector-mediated siRNA delivery methods it is now possible to make transgenic animals that can silence gene expression stably. These technologies point to the usefulness of RNAi for drug discovery.

RNAi can be rationally designed to block the expression of any target gene, including genes for which traditional small molecule inhibitors cannot be found. Areas of therapeutic applications include virus infections, cancer, genetic disorders and neurological diseases. Side effects can result from unintended interaction between an siRNA compound and an unrelated host gene. If RNAi compounds are designed poorly, there is an increased chance for non-specific interaction with host genes that may cause adverse effects in the host.

Regulatory, safety and patent issues are discussed. There are no major safety concerns and regulations are in preliminary stages as the clinical trials are just starting. Many of the patents are still pending.

The markets for RNAi are difficult to define as no RNAi-based product is approved yet but several are in clinical trials. The major use of RNAi reagents is in research but it partially overlaps that of drug discovery and therapeutic development. Various markets relevant to RNAi are analyzed from 2009 to 2019. Markets are also analyzed according to breakdown of technologies and use of siRNAs, miRNAs, etc.

Profiles of 156 companies involved in developing RNAi technologies are presented along with 204 collaborations. They are a mix of companies that supply reagents and technologies (nearly half of all) and companies that use the technologies for drug discovery. Out of these, 30 are developing RNAi-based therapeutics and 26 are involved in microRNAs. The bibliography contains selected 500 publications that are cited in the report. The text is supplemented with 35 tables and 10 figures.

TABLE OF CONTENTS

0. Executive Summary 15

1. Technologies for suppressing gene function 17

Introduction 17

DNA transcription 17

RNA 17

Non-coding RNA 17

RNA research and potential applications 18

Role of RNA in regulation of the dihydrofolate reductase gene 19

Gene regulation 19

Post-transcriptional regulation of gene expression 20

Alternative RNA splicing 21

Technologies for gene suppression 21

Antisense oligonucleotides 21

Transcription factor decoys 22

Aptamers 22

Ribozymes 23

Aptazymes 23

RNA aptamers vs allosteric ribozymes 23

RNA Lasso 24

Peptide nucleic acid 24

PNA-DNA chimeras 25

Locked nucleic acid 25

Gene silencing 25

Post-transcriptional gene silencing 26

TargeTron? technology for gene knockout 26

Definitions and terminology of RNAi 26

RNAi mechanisms 27

Non-promoter-associated small RNAs 29

Piwi-interacting RNAs in germ cell development 30

Relation of RNAi to junk DNA 30

RNA editing and RNAi 31

Historical landmarks in the development of RNAi 31

2. RNAi Technologies 33

Introduction 33

Comparison of antisense and RNAi 33

Advantages of antisense over siRNAs 33

Advantages of siRNAs over antisense 34

RNA aptamers vs siRNA 34

RNA Lassos versus siRNA 34

Concluding remarks on antisense vs RNAi 35

ssRNAi 35

Antisense vs DNP-ssRNA and DNP-siRNA 35

LNA and RNAi 36

LNA for gene suppression 36

Comparison of LNA and RNAi 37

Use of siLNA to improve siRNA 37

RNAi versus small molecules 37

RNAi in vivo 37

Cre-regulated RNAi in vivo 38

RNAi kits 38

ShortCut™ RNAi Kit 38

HiScribe™ RNAi Transcription Kit 39

pSUPER RNAi system 39

Si2 Silencing Duplex 40

Techniques for measuring RNAi-induced gene silencing 40

Application of PCR in RNAi 40

Real-time quantitative PCR 41

Assessment of the silencing effect of siRNA by RT-PCR 41

Fluorescence resonance energy transfer probe for RNA interactions 42

Bioinformatics tools for design of siRNAs 42

Random siRNA design 42

Rational siRNA design 42

The concept of pooling siRNAs 44

Criteria for rational siRNA design 44

BLOCK-iT RNAi Designer 44

QIAGEN's 2-for-Silencing siRNA Duplexes 45

Designing vector-based siRNA 45

iRNAChek for designing siRNA 45

TROD: T7 RNAi Oligo Designer 45

siDirect: siRNA design software 46

Prediction of efficacy of siRNAs 46

Algorithms for prediction of siRNA efficacy 46

siRNA databases 46

Production of siRNAs 47

Chemical synthesis of short oligonucleotides 47

In vitro transcription 47

Generation of siRNA in vivo 48

siRNA:DNA hybrid molecules 48

Chemical modifications of siRNAs 48

Sugar modifications of siRNA 49

Phosphate linkage modifications of siRNA 49

Modifications to the siRNA overhangs 49

Modifications to the duplex architecture 50

Applications of chemical modification of siRNAs 50

Synthetic RNAs vs siRNAs 51

Specificity of siRNAs 51

Asymmetric interfering RNA 51

Genome-wide data sets for the production of esiRNAs 52

ddRNAi for inducing RNAi 52

ddRNAi technology 52

Advantages of ddRNAi over siRNA 53

Short hairpin RNAs 54

siRNA versus shRNA 54

Circular interfering RNA 55

Expressed interfering RNA 56

RNA-induced transcriptional silencing complex 56

Inhibition of gene expression by antigene RNA 57

RNAi vs mRNA modulation by small molecular weight compounds 57

3. MicroRNA 59

Introduction 59

miRNA and RISC 61

Role of the microprocessor complex in miRNA 61

miRNAs compared to siRNAs 62

miRNA and stem cells 63

Influence of miRNA on stem cell formation and maintenance 63

Role of miRNAs in gene regulation during stem cell differentiation 63

miRNA databases 64

Sanger miRBase miRNA sequence database 64

Mapping miRNA genes 64

A database of ultraconserved sequences and miRNA function 65

A database for miRNA deregulation in human disease 65

An database of miRNA-target interactions 65

Role of miRNA in gene regulation 66

Control of gene expression by miRNA 66

miRNA-mediated translational repression involving Piwi 67

Transcriptional regulators of ESCs control of miRNA gene expression 67

Mechanism of miRNAs-induced silencing of gene expression 67

miRNA diagnostics 68

Biochemical approach to identification of miRNA 68

Computational approaches for the identification of miRNAs 68

LNA probes for exploring miRNA 69

Microarrays for analysis of miRNA gene expression 69

Microarrays vs quantitative PCR for measuring miRNAs 70

miRNAs as biomarkers of hepatotoxicity 70

Modification of in situ hybridization for detection of miRNAs 70

Nuclease Protection Assay to measure miRNA expression 71

Real-time PCR for expression profiling of miRNAs 71

Targeting of miRNAs with antisense oligonucleotides 71

Silencing miRNAs by antagomirs 72

New tools for miRNA silencing 72

miRNA-regulated lentiviral vectors 72

miRNAs as drug targets 73

miRNAs as targets for antisense drugs 73

Challenges facing use of miRNAs as drug targets 73

Target specificity of miRNAs 74

Prediction of miRNA targets 74

Role of miRNA in human health and disease 75

Role of miRNAs in regulation of hematopoiesis 75

Role of miRNA depletion in tissue regeneration 76

Role of miRNA in regulation of aging 76

Role of miRNA in inflammation 76

Role of miRNAs in regulation of immune system 77

Role of miRNA in the cardiovascular system 77

Role of miRNAs in development of the cardiovascular system 77

Role of miRNAs in angiogenesis 78

Role of miRNAs in cardiac hypertrophy and failure 78

Role of miRNAs in conduction and rhythm disorders of the heart 78

miRNA-based approach for reduction of hypercholesterolemia 79

miRNA-based approach for restenosis following angioplasty 79

miRNAs as therapeutic targets for cardiovascular diseases 79

Concluding remarks and future prospects of miRNA in the cardiovascular system 80

Role of miRNAs in the nervous system 80

miRNAs in neurodegenerative disorders 80

miRNAs as biomarkers of Alzheimer's disease 81

miRNA and schizophrenia 81

miRNAs and retinal neurodegenerative disorders 81

Role of miRNA in viral infections 82

Role of miRNA in HSV-1 latency 82

miRNA and autoimmune disorders 82

miRNA in systemic lupus erythematosus 82

miRNA and skin disorders 83

Role of miRNA in inflammatory skin disorders 83

Role of miRNAs in cancer 83

miRNAs linked to the initiation and progression of cancer 83

Oncomirs 83

Linking miRNA sequences to cancer using RNA samples 84

Role of miRNAs in viral oncogenesis 85

miRNA genes in cancer 85

miRNAs, embryonic stem cells and cancer 86

miRNAs and cancer metastases 86

Role of miRNAs in cancer diagnosis 87

Cancer miRNA signature 87

miRNA biomarkers in cancer 87

Diagnostic value of miRNA in cancer 88

Prognostic value of miRNA in cancer 88

miRNAs as basis of cancer therapeutics 88

Antisense oligonucleotides targeted to miRNA 89

Role of miRNAs in adoptive immunotherapy of cancer 89

Restoration of tumor suppressor miRNA may inhibit cancer 89

Role of miRNAs in various cancers 90

miRNA and brain cancer 90

miRNA and breast cancer 90

miRNA and colorectal cancer 91

miRNA and hematological malignancies 91

miRNA and hepatocellular carcinoma 93

miRNA and lung cancer 93

miRNA and nasopharyngeal carcinoma 94

miRNA and ovarian cancer 94

miRNA and pancreatic cancer 95

miRNA and prostatic cancer 96

miRNA and thyroid cancer 96

Future prospects of miRNA 96

Companies involved in miRNA 97

4. Methods of delivery in RNAi 99

Introduction 99

Methods of delivery of oligonucleotides 99

Oral and rectal administration 100

Pulmonary administration 100

Targeted delivery to the CNS 100

High flow microinfusion into the brain parenchyma 101

Intracellular guidance by special techniques 101

Biochemical microinjection 102

Liposomes-mediated oligonucleotide delivery 102

Polyethylenimine-mediated oligonucleotide delivery 102

Delivery of TF Decoys 102

Biodegradable microparticles 103

Microparticles 103

Nanoparticles 103

siRNA delivery technologies 103

Local delivery of siRNA 104

In vivo delivery of siRNAs by synthetic vectors 105

Intracellular delivery of siRNAs 105

Protamine-antibody fusion proteins for delivery of siRNA to cells 105

Protein transduction domains 106

MPG-based delivery of siRNA 106

Delivery of siRNAs with aptamer-siRNA chimeras 106

Phosphorothioate stimulated cellular delivery of siRNA 107

Targeted delivery of siRNAs by lipid-based technologies 107

Delivery of siRNA-lipoplexes 107

Lipidoids for delivery of siRNAs 108

NeoLipid™ technology 108

siFECTamine? 108

Systemic in vivo delivery of lipophilic siRNAs 109

Systemic delivery of siRNAi by lipid nanoparticles 109

Electroporation 109

Nucleofactor technology 110

Intravascular delivery of siRNA 110

27mer siRNA duplexes for improved delivery and potency 111

TransIT-TKO? 111

DNA-based plasmids for delivery of siRNA 112

Convergent transcription 113

PCR cassettes expressing siRNAs 113

Genetically engineered bacteria for delivery of shRNA 113

Viral vectors for delivery of siRNA 113

Adenoviral vectors 114

Adeno-associated virus vectors for shRNA expression 114

Baculovirus vector 114

Lentiviral vectors 115

Retroviral delivery of siRNA 116

Transkingdom RNAi delivery by genetically engineered bacteria 116

Delivery of siRNA without a vector 116

Cell-penetrating peptides for delivery of siRNAs 117

Role of nanobiotechnology in siRNA delivery 117

Chitosan-coated nanoparticles for siRNA delivery 117

Delivery of gold nanorod-siRNA nanoplex to dopaminergic neurons 118

Lipidic aminoglycoside as siRNA nanocarrier 118

Lipid nanoparticles-mediated siRNA delivery 118

Nanosize liposomes for delivery of siRNA 119

PAMAM dendrimers for siRNA delivery 119

Polyethylenimine nanoparticles for siRNA delivery 119

Polycation-based nanoparticles for siRNA delivery 120

Quantum dots to monitor siRNA delivery 120

Targeted delivery of siRNAs to specific organs 121

siRNA delivery to the CNS 121

siRNA delivery to the liver 122

siRNAdelivery to the lungs 122

Control of RNAi and siRNA levels 122

siRNA pharmacokinetics in mammalian cells 123

Mathematical modeling for determining the dosing schedule of siRNA 123

Assessing siRNA pharmacodynamics in animal models 124

Research on siRNA delivery funded by the NIH 124

Companies involved in delivery technologies for siRNA 125

5. RNAi in Research 129

Introduction 129

Basic RNAi research 129

Genes and lifespan 129

Antiviral role of RNAi in animal cells 129

Silencing snoRNA genes 129

Profiling small RNAs 130

Study of signaling pathways 130

RNAi for research in neuroscience 130

Use of RNAi to study insulin action 131

Detection of cancer mutations 131

Loss-of-function genetic screens 131

Inducible and reversible RNAi 132

Combination of siRNA with green fluorescent protein 132

RNAi and environmental research 132

Applied RNAi research 133

RNAi for gene expression studies 133

Microarrays for measuring gene expression in RNAi 133

RNAi for functional genomic analysis 134

RNAi studies on C. elegans 134

RNAi studies on Drosophila 135

RNAi in planaria 135

Testing the specificity of RNAi 136

Tissue-specific RNAi 136

siRNA-mediated gene silencing 136

RNAi libraries 137

Universal plasmid siRNA library 138

pDual library using plasmid vector 138

pHippy plasmid vector library 138

siRNA library including miRNAs 138

siRNA libraries using pRetroSuper vector 139

siRNA produced by enzymatic engineering of DNA 139

shRNA libraries 139

Enzymatic production of RNAi library 140

RNAi and alternative splicing 141

RNAi in animal development 141

RNAi for creating transgenic animals 141

RNAi for creating models of neurological disorders 142

Research support for RNAi in US 142

RNAi for toxicogenomics 142

Role of RNAi in the US biodefense research 143

The RNAi Consortium 143

Research support for RNAi in Europe 144

European Union for RNA Interference Technology 144

Research support of RNAi 144

Role of RNAi in MitoCheck project 145

RNAi Global Initiative 145

6. RNAi in drug discovery 149

Basis of RNAi for drug discovery 149

Use of siRNA libraries to identify genes as therapeutic targets 149

Role of siRNAs in drug target identification 149

Use of a genome-wide, siRNA library for drug discovery 150

Use of arrayed adenoviral siRNA libraries for drug discovery 150

RNAi as a tool for assay development 150

Targeting human kinases with an siRNAi library 151

Challenges of drug discovery with RNAi 151

Express Track(SM) siRNA Drug Discovery Program 151

Genome-wide siRNA screens in mammalian cells 152

Natural antisense and ncRNA as drug targets 152

RNAi for target validation 153

Delivering siRNA for target validation in vivo 153

Off-target effects of siRNA-mediated gene silencing 155

Bioinformatic approach to off-target effects 156

Validation of oncology targets discovered through RNAi screens 156

Selection of siRNA versus shRNA for target validation 156

Application of RNAi to the druggable genome 157

Application of siRNA during preclinical drug development 157

siRNAs vs small molecules as drugs 158

siRNAs vs antisense drugs 158

RNAi technology in plants for drug discovery and development 159

Application of RNAi to poppy plant as source of new drugs 159

7. Therapeutic applications of RNAi 161

Introduction 161

Potential of RNAi-based therapies 162

In vitro applications of siRNA 162

In vivo applications of RNAi 163

RNAi and cell therapy 163

Gene inactivation to study hESCs 164

RNAi and stem cells 164

Cell therapy for immune disorders 165

RNAi gene therapy 165

Drug-inducible systems for control of gene expression 165

Potential side effects of RNAi gene therapy 166

Systemic delivery of siRNAs 166

In vivo RNAi therapeutic efficacy in animal models of human diseases 167

Virus infections 167

RNAi approaches to viral infections 168

Delivery of siRNAs in viral infections 169

RNAi applications in HIV 169

A multiple shRNA approach for silencing of HIV-1 170

Anti-HIV shRNA for AIDS lymphoma 170

Aptamer-mediated delivery of anti-HIV siRNAs 170

Bispecific siRNA constructs 170

Role of the nef gene during HIV-1 infection and RNAi 171

siRNA-directed inhibition of HIV-1 infection 171

Synergistic effect of snRNA and siRNA 172

Targeting CXCR4 with siRNAs 172

Targeting CCR5 with siRNAs 172

Concluding remarks on RNAi approach to HIV/AIDS 173

Influenza 173

Inhibition of influenza virus by siRNAs 174

Delivery of siRNA in influenza 175

Challenges and future prospects of siRNAs for influenza 175

Respiratory syncytial and parainfluenza viruses 176

Coronavirus/severe acute respiratory syndrome 177

Herpes simplex virus 2 177

Hepatitis B 177

Hepatitis C virus 178

Cytomegalovirus 179

siRNA vs antisense oligonucleotides for viral infections 180

siRNA against methicillin-resistant S. aureus 180

RNAi-based rational approach to antimalarial drug discovery 181

Inhibiting the growth of malarial parasite by heme-binding DNA aptamers 181

siRNA-based antimalarial therapeutics 181

RNAi applications in oncology 182

Inhibition of oncogenes 182

RNAi approach to study TRAIL 184

Modification of alternative splicing in cancer 184

Allele-specific inhibition 184

siRNAs for anticancer drug discovery 185

siRNAs for inducing cancer immunity 186

siRNAs for inhibition of angiogenesis 187

siRNA targeting the R2 subunit of ribonucleotide reductase 187

siRNA for cancer chemoprevention 187

Onconase 188

Drug delivery issues in managing cancer by RNAi approach 188

siHybrids vs siRNAs as anticancer agents 189

Nanobiotechnology-based delivery of siRNAs 189

Lipid nanoparticle-based delivery of anticancer siRNAs 189

Minicells for targeted delivery of nanoscale anticancer therapeutics 190

Nanoimmunoliposome-based system for targeted delivery of siRNA 190

Polymer nanoparticles for targeted delivery of anticancer siRNA 190

RNA nanotechnology for delivery of cancer therapeutics 191

Targeted delivery of a nanoparticle-siRNA complex in cancer patients 191

RNAi-based treatment of various cancer types 192

RNAi-based therapy of brain cancer 192

RNAi in breast cancer 194

Enhancing efficacy of hyperthermia/chemotherapy in cervical cancer 194

RNAi and colorectal cancer 194

RNAi and Ewing's sarcoma 195

RNAi and leukemias 195

RNAi and lung cancer 196

RNAi and melanoma 196

RNAi and pancreatic cancer 197

RNAi and prostate cancer 197

Overcoming drug resistance in cancer 198

Targeting fusion proteins in cancer 198

Increasing chemosensitivity by RNAi 198

Genetic disorders 199

RNAi for skin disorders 199

Experimental studies for RNAi applications in skin disorders 199

Clinical applications of RNAi in skin disorders 200

Pachyonychia congenita 200

Neurological disorders 201

RNAi for neurodegenerative disorders 202

Alzheimer's disease 202

Parkinson's disease 203

Amyotrophic lateral sclerosis 203

Prion diseases 204

Polyglutamine-induced neurodegeneration 205

Fragile X syndrome and RNAi 205

RNAi-based therapy for Huntington's disease 206

Combination of RNAi and gene therapy to prevent neurodegenerative disease 207

Role of RNAi in pain therapy 207

Role of RNAi in repair of spinal cord injury 208

Role of RNAi in treatment of multiple sclerosis 208

siRNA for Duchenne muscular dystrophy 209

siRNA for dystonia 209

RNAi in ophthalmology 209

Age related macular degeneration 209

Current treatment of AMD 210

RNAi-based treatments for AMD 211

Diabetic retinopathy 212

Retinitis pigmentosa 213

RNAi and metabolic disorders 213

RNAi and obesity 213

Genes and regulation of body fat 213

RNAi and diabetes 213

Use of siRNAs to study glucose transporter 214

Use of RNAi to study genes in animal models of diabetes 214

RNAi for drug discovery in diabetes 214

A miRNA that regulates insulin secretion 215

RNAi in hematology 216

Stem cell-based gene therapy and RNAi for sickle cell disease 216

RNAi and disorders of the immune system 217

siRNA applications in immunology 217

Use of RNAi in transplantation 218

RNAi for cardiovascular disorders 218

RNAi for hypercholesterolemia 219

siRNA targeting NADPH oxidase in cardiovascular diseases 219

siRNA for study and treatment of ischemia-reperfusion injury 220

RNAi in respiratory disorders 220

siRNA for cystic fibrosis 220

siRNA for asthma 221

RNAi for musculoskeletal disorders 221

RNAi for rheumatoid arthritis 221

RNAi for bone disorders 222

RNAi for treatment of osteoporosis 222

Clinical trials of RNAi-based therapies 223

Improving efficacy of siRNAs for clinical trials by improved delivery 224

Role of RNAi in development of personalized medicine 224

Future prospects of RNAi 225

Challenges for the development of RNAi-based therapeutics 225

8. Safety, regulatory and patent issues 227

Introduction 227

Limitations and drawbacks of RNAi 227

Adverse effects of RNAi 227

Effect of siRNAs on interferon response 228

Detection of interferon response 228

Prevention of the interferon response in RNAi 229

Overcoming the innate immune response to siRNAs 229

Selection of siRNAs to improve specificity and efficacy 230

Regulatory issues relevant to RNAi 230

RNAi patents 231

Companies with strong patent position 231

Alnylam 231

Benitec 234

Intradigm 234

Sirna Therapeutics 234

9. Markets for RNAi Technologies 237

Introduction 237

Current and future market potential for RNAi technologies 237

RNAi reagents 238

RNAi-based drug discovery and target validation 238

RNAi-based development of therapeutics 238

RNAi market potential according to therapeutic areas 238

Market for viral infections 239

Market for cancer 240

Market for age related macular degeneration 240

Unmet needs in RNAi 240

Strategies for marketing RNAi 241

Choosing optimal indications 241

Strategies according to the trends in healthcare in the next decade 242

Concluding remarks 243

10. Companies involved in RNAi Technologies 245

Introduction 245

Major players in RNAi 248

Profiles of companies 249

Collaborations 430

11. References 437

Tables

Table 1 1: Classification of small RNA molecules 27

Table 1 2: Mechanisms of small RNAs involved in gene silencing 28

Table 1 3: Historical landmarks in the evolution of RNAi 31

Table 2 1: RNAi versus small molecules 37

Table 2 2: Providers of software for siRNA design 43

Table 2 3: Methods for the production of siRNAs 47

Table 2 4: Advantages and limitations of methods of shRNA-derived siRNA knockdown 55

Table 2 5: Comparison of eiRNA with siRNA 56

Table 3 1: Methods for miRNA target prediction 75

Table 3 2: miRNA expression in neurodegenerative diseases 80

Table 3 3: Dysregulation of miRNA expression in epithelial cancers 84

Table 3 4: Companies involved in miRNA diagnostics and therapeutics 97

Table 4 1: Methods of delivery of oligonucleotides 99

Table 4 2: Methods of delivery of siRNA 104

Table 4 3: Companies developing siRNA delivery technologies 125

Table 5 1: RNAi libraries 137

Table 6 1: Delivery of siRNAs in vivo for target validation 154

Table 6 2: Selection of siRNA versus shRNA for target validation 157

Table 7 1: RNAi-based therapeutic approaches 162

Table 7 2: In vivo RNAi therapeutic efficacy in animal models of human diseases 167

Table 7 3: Inhibition of viral replication by RNAi 168

Table 7 4: Cancer-associated genes that can be targeted by RNAi 183

Table 7 5: Neurological disorders that have been studied by using RNAi 201

Table 7 6: Clinical trials of RNAi-based therapeutics 223

Table 9 1: RNAi markets according to technologies and reagents 2009-2019 237

Table 9 2: Markets for RNAi therapy for selected diseases: years 2009-2019 239

Table 10 1: RNAi reagent, technology and service companies 245

Table 10 2: Pharmaceutical companies using RNAi for drug discovery and development 246

Table 10 3: Biotechnology companies using RNAi for drug discovery and development 247

Table 10 4: Companies developing RNAi-based therapeutic products 248

Table 10 5: Major players in RNAi 248

Table 10 6: RNAi products of Benitec 267

Table 10 7: Proprietary reagents of ImuThes 319

Table 10 8: Product pipeline of Silence Therapeutics 401

Table 10 9: Collaborations in RNAi technologies 430

Figures

Figure 1 1: Relationship of DNA, RNA and protein in the cell 20

Figure 1 2: Schematic of suppression of gene expression by RNAi 28

Figure 2 1: Overview of ShortCut RNAi Kit 39

Figure 2 2: Gene silencing by RNAi induced with ddRNAi 53

Figure 3 1: A schematic miRNA pathway 59

Figure 3 2: Molecular mechanisms of miRNA generation 60

Figure 7 1: Targeting disease by RNAi 161

Figure 7 2: Role of RNAi in personalized medicine 224

Figure 8 1: Problems with use of synthetic siRNAs and measures to prevent them 228

Figure 9 1: Unmet needs in RNAi technologies 241

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