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RNAi - Technologies, Markets & Companies

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  • 527 Pages
  • November 2021
  • Region: Global
  • Jain PharmaBiotech
  • ID: 4748172

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 the design and methods of manufacture of siRNA reagents. These include chemical synthesis by in vitro transcription and the 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 short hairpins that can inhibit the mRNAs. Expressed interfering RNA (eiRNA) is used to express dsRNA intracellularly from DNA plasmids.

The 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 the 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 specific phenotypes. Several methods of gene expression analysis are available and there is still a 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 use 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. Research at academic centers that is relevant to RNAi-based therapeutics is mentioned.

Regulatory, safety and patent issues are discussed. Side effects can result from unintended interaction between a 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. However, there are no major safety concerns and regulations are in the preliminary stages as the clinical trials are still ongoing and there are no marketed products. 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 2018 to 2028. Markets are also analyzed according to technologies and the use of siRNAs, miRNAs, etc.

Profiles of 168 companies involved in developing RNAi technologies are presented along with 231 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, 34 are developing RNAi-based therapeutics and 36 are involved in microRNAs. The bibliography contains selected 650 publications that are cited in the report. The text is supplemented with 39 tables and 18 figures.

This report contains information on the following areas:

  • Technologies for suppressing gene function
  • RNAi Technologies
  • microRNA
  • Methods of delivery in RNAi
  • RNAi in Research & Drug Discovery
  • Therapeutic applications of RNAi
  • Safety, Regulatory and Patent Issues
  • Markets for RNAi Technologies
  • Companies

Table of Contents

Executive Summary

1. Technologies for suppressing gene function

  • Introduction
  • DNA transcription
  • RNA
  • Non-coding RNA
  • RNA research and potential applications
  • Role of RNA in regulation of the dihydrofolate reductase gene
  • Gene regulation
  • Post-transcriptional regulation of gene expression  
  • RNA splicing  
  • Technologies for gene suppression  
  • Antisense oligonucleotides  
  • Phosphorodiamidate morpholino oligomers
  • Transcription factor decoys
  • Aptamers  
  • Ribozymes
  • Aptazymes
  • RNA aptamers vs allosteric ribozymes  
  • Peptide nucleic acid
  • PNA-DNA chimeras
  • Locked nucleic acid
  • Long noncoding RNAs
  • Gene silencing
  • Post-transcriptional gene silencing
  • Small noncoding RNAs
  • TargeTron technology for gene knockout
  • Definitions and terminology of RNAi
  • RNAi mechanisms
  • RNAi oligonucleotides  
  • Non-promoter-associated small RNAs 
  • Piwi-interacting RNAs in germ cell development
  • Relation of RNAi to junk DNA
  • RNAi and epigenetic mechanisms
  • RNA editing and RNAi  
  • Historical landmarks in the development of RNAi

2. RNAi Technologies  

  • Introduction
  • Comparison of antisense and RNAi  
  • Advantages of antisense over siRNAs
  • Advantages of siRNAs over antisense
  • RNA aptamers vs siRNA  
  • RNA Lassos versus siRNA
  • Concluding remarks on antisense vs RNAi
  • PMOs vs antisense and siRNAs
  • ssRNAi
  • Antisense vs DNP-ssRNA and DNP-siRNA
  • LNA and RNAi. 
  • LNA for gene suppression
  • Comparison of LNA and RNAi
  • Use of siLNA to improve siRNA.
  • RNAi versus small molecules
  • RNAi in vivo
  • Cre-regulated RNAi in vivo  
  • RNAi kits  
  • ShortCut™ RNAi Kit
  • HiScribe™ RNAi Transcription Kit
  • pSUPER RNAi system  
  • Si2 Silencing Duplex
  • Techniques for measuring RNAi-induced gene silencing  
  • Application of PCR in RNAi
  • Real-time quantitative PCR
  • Assessment of the silencing effect of siRNA by RT-PCR  
  • Fluorescence resonance energy transfer probe for RNA interactions
  • Bioinformatics tools for design of siRNAs
  • Random siRNA design
  • Rational siRNA design
  • The concept of pooling siRNAs
  • Criteria for rational siRNA design
  • BLOCK-iT RNAi Designer
  • QIAGEN's 2-for-Silencing siRNA Duplexes
  • Designing vector-based siRNA
  • iRNAChek for designing siRNA
  • TROD: T7 RNAi Oligo Designer
  • siDirect: siRNA design software  
  • Prediction of efficacy of siRNAs
  • Algorithms for prediction of siRNA efficacy
  • siRNA databases
  • Production of siRNAs
  • Chemical synthesis of short oligonucleotides
  • In vitro transcription  
  • Generation of siRNAs in vivo
  • UsiRNAs
  • siRNA:DNA hybrid molecules
  • Chemical modifications of siRNAs
  • Sugar modifications of siRNA  
  • Phosphate linkage modifications of siRNA
  • Modifications to the siRNA overhangs  
  • Modifications to the duplex architecture
  • Applications of chemical modification of siRNAs
  • Synthetic RNAs vs siRNAs
  • Specificity of siRNAs
  • Asymmetric interfering RNA
  • Genome-wide data sets for the production of esiRNAs
  • ddRNAi for inducing RNAi
  • ddRNAi technology
  • Advantages of ddRNAi over siRNA
  • Short hairpin RNAs  
  • siRNA versus shRNA
  • Circular interfering RNA  
  • Expressed interfering RNA
  • RNA-induced transcriptional silencing complex
  • Inhibition of gene expression by antigene RNA
  • RNAi vs mRNA modulation by small molecular weight compounds  
  • saRNA for transcriptional activation
  • Synthetic nucleic acid drugs for selective tissue targeting  

3. MicroRNA

  • Introduction
  • Circular RNA and miRNA  
  • miRNA and RISC  
  • Role of the microprocessor complex in miRNA
  • miRNAs compared to siRNAs
  • miRNA and stem cells  
  • Influence of miRNA on stem cell formation and maintenance
  • Role of miRNAs in gene regulation during stem cell differentiation
  • miRNA databases
  • Sanger miRBase miRNA sequence database  
  • Mapping miRNA genes
  • A database of ultraconserved sequences and miRNA function  
  • A database for miRNA deregulation in human disease
  • An database of miRNA-target interactions
  • Role of miRNA in gene regulation
  • Control of gene expression by miRNA
  • miRNA-mediated translational repression involving Piwi
  • Transcriptional regulators of ESCs control of miRNA gene expression. 
  • Mechanism of miRNAs-induced silencing of gene expression
  • miRNA diagnostics
  • Biochemical approach to identification of miRNA
  • Computational approaches for the identification of miRNAs
  • LNA probes for exploring miRNA  
  • miR-TRAP to identify miRNA targets in vivo
  • Microarrays for analysis of miRNA gene expression
  • Microarrays vs quantitative PCR for measuring miRNAs 
  • miRNAs as biomarkers of hepatotoxicity
  • Modification of in situ hybridization for detection of miRNAs
  • Nuclease Protection Assay to measure miRNA expression
  • Real-time PCR for expression profiling of miRNAs
  • Significance of miRNAs in diagnostics
  • Targeting of miRNAs with antisense oligonucleotides
  • Silencing miRNAs by antagomirs  
  • New tools for miRNA silencing
  • Use of HAPIscreen for identification of aptamers against pre-miRNAs
  • miRNA-regulated lentiviral vectors  
  • miRNAs as drug targets
  • miRNAs as targets for antisense drugs  
  • Challenges facing use of miRNAs as drug targets
  • Target specificity of miRNAs
  • Prediction of miRNA targets
  • Role of miRNA in human health and disease
  • Role of miRNAs in regulation of hematopoiesis. 
  • Role of miRNA depletion in tissue regeneration  
  • Role of miRNA in regulation of aging
  • Role of miRNA in inflammation
  • Role of miRNAs in regulation of immune system
  • Role of miRNA in diabetes
  • Role of miRNA in the cardiovascular system
  • Role of miRNAs in development of the cardiovascular system  
  • Role of miRNAs in angiogenesis
  • Role of miRNA in atherosclerosis  
  • Role of miRNAs in cardiac hypertrophy and failure
  • Role of miRNA in cardiomyopathy
  • Role of miRNAs in conduction and rhythm disorders of the heart  
  • Diagnostic and prognostic value of miRNAs in acute coronary syndrome
  • miRNA-based approaches for reduction of hypercholesterolemia  
  • miRNA-based approach for restenosis following angioplasty
  • miRNA gene therapy for ischemic heart disease
  • miRNAs as therapeutic targets for cardiovascular diseases  
  • Concluding remarks and future prospects of miRNA in the cardiovascular system. 
  • Role of miRNAs in diseases of the eye
  • Pathological ocular neovascularization  
  • Role of miRNAs in diabetic retinopathy
  • Role of miRNAs in glaucoma
  • Role of miRNA in corneal scarring
  • Role of miRNAs in the nervous system.
  • miRNAs and addiction
  • miRNAs in neurodegenerative disorders
  • miRNAs as biomarkers of Alzheimer’s disease
  • miRNAs in Parkinson disease  
  • miRNAs in Huntington’s disease  
  • miRNAs in ALS  
  • miRNAs as biomarkers of prion-induced neurodegeneration
  • miRNAs and retinal neurodegenerative disorders  
  • miRNA and stroke
  • miRNAs and schizophrenia
  • Role of miRNAs in neuroprotection
  • Role of miRNAs in viral infections
  • Role of miRNA in HSV-1 latency
  • miRNA and autoimmune disorders
  • miRNA in rheumatoid arthritis
  • miRNA in systemic lupus erythematosus
  • miRNAs in gastrointestinal disorders
  • miRNA-based therapies for the irritable bowel syndrome  
  • miRNA-based therapies for the inflammatory bowel disease  
  • miRNA and skin disorders  
  • Role of miRNA in inflammatory skin disorders  
  • Role of miRNA in hypertrophic scarring of the skin
  • Role of miRNAs in cancer
  • miRNAs linked to the initiation and progression of cancer  
  • Oncomirs
  • Linking miRNA sequences to cancer using RNA samples
  • Role of miRNAs in viral oncogenesis
  • miRNA genes in cancer
  • miRNAs interaction with p53
  • miRNAs, embryonic stem cells and cancer
  • miRNAs and cancer metastases
  • Role of miRNAs in cancer diagnosis
  • Cancer miRNA signature  
  • miRNA biomarkers in cancer
  • Diagnostic value of miRNA in cancer  
  • Prognostic value of miRNA in cancer  
  • miRNA-based cancer therapeutics  
  • Antisense oligonucleotides targeted to miRNA
  • Role of miRNAs in adoptive immunotherapy of cancer
  • Restoration of tumor suppressor miRNAs to inhibit cancer
  • Delivery strategies for miRNA modulators in cancer
  • Role of miRNAs in various cancers 
  • miRNA and brain tumors  
  • miRNAs and CNS tumors in children  
  • miRNAs and pituitary tumors
  • miRNA and breast cancer
  • miRNA and colorectal cancer
  • miRNA and gastrointestinal cancer
  • miRNA and leukemia
  • miRNA and lymphomas
  • miRNA and hepatocellular carcinoma
  • miRNA and lung cancer
  • miRNA and nasopharyngeal carcinoma  
  • miRNA and ovarian cancer
  • miRNA and pancreatic cancer
  • miRNA and prostatic cancer 
  • miRNA and thyroid cancer
  • Companies involved in miRNA
  • Status of therapeutic development of miRNAs
  • Concluding remarks and future of miRNA therapeutics  

4. Methods of delivery in RNAi  

  • Introduction  
  • Methods of delivery of oligonucleotides
  • Oral and rectal administration
  • Pulmonary administration
  • Targeted delivery to the CNS
  • High flow microinfusion into the brain parenchyma  
  • Intracellular guidance by special techniques
  • Biochemical microinjection
  • Liposomes-mediated oligonucleotide delivery  
  • Polyethylenimine-mediated oligonucleotide delivery
  • Delivery of TF Decoys
  • Biodegradable microparticles
  • Microparticles
  • Nanoparticles
  • Self-delivering rxRNA
  • siRNA delivery technologies. 
  • Local delivery of siRNA
  • In vivo delivery of siRNAs by synthetic vectors
  • Intracellular delivery of siRNAs  
  • Delivery of siRNAs with aptamer-siRNA chimeras
  • MPG-based delivery of siRNA
  • Protamine-antibody fusion proteins for delivery of siRNA to cells
  • Protein transduction domains
  • Phosphorothioate stimulated cellular delivery of siRNA
  • Targeted delivery of siRNAs by lipid-based technologies
  • Delivery of siRNA-lipoplexes
  • Lipidoids for delivery of siRNAs
  • Lipid-based Unlocked Nucleomonomer Agent  
  • NeoLipid™ technology
  • siFECTamine
  • Systemic in vivo delivery of lipophilic siRNAs  
  • Challenges and future prospects of lipid-based siRNA delivery  
  • Electroporation
  • Nucleofactor technology
  • Visualization of electrotransfer of siRNA at single cell level
  • Intravascular delivery of siRNA  
  • 27mer siRNA duplexes for improved delivery and potency
  • TransIT-TKO
  • DNA-based plasmids for delivery of siRNA
  • Convergent transcription  
  • PCR cassettes expressing siRNAs
  • Genetically engineered bacteria for delivery of shRNA
  • Viral vectors for delivery of siRNA  
  • Adenoviral vectors  
  • Adeno-associated virus vectors for shRNA expression  
  • Baculovirus vector
  • Lentiviral vectors
  • Retroviral delivery of siRNA  
  • Transkingdom RNAi delivery by genetically engineered bacteria
  • Delivery of siRNA without a vector
  • Cell-penetrating peptides for delivery of siRNAs
  • Role of nanobiotechnology in siRNA delivery
  • Chitosan-coated nanoparticles for siRNA delivery
  • Cyclodextrin nanoparticles
  • Delivery of gold nanorod-siRNA nanoplex to dopaminergic neurons
  • Lipidic aminoglycoside as siRNA nanocarrier
  • Lipid nanoparticles-mediated siRNA delivery
  • Nanoparticles for intracellular delivery of siRNA  
  • Nanosize liposomes for delivery of siRNA
  • PAMAM dendrimers for siRNA delivery
  • PEG-PCL-DEX polymersome-protamine vector
  • Polyethylenimine nanoparticles for siRNA delivery
  • Polycation-based nanoparticles for siRNA delivery
  • Quantum dots to monitor siRNA delivery
  • siRNA-nanoparticle conjugates for improving stability in serum
  • Systemic delivery of siRNAi by lipid nanoparticles
  • Topical delivery of siRNA-nanoparticle conjugates
  • Targeted delivery of siRNAs to specific organs
  • siRNA delivery to the CNS
  • siRNA delivery to the liver
  • siRNA delivery to the lungs  
  • Control of RNAi and siRNA levels
  • iRNA pharmacokinetics in mammalian cells
  • Mathematical modeling for determining the dosing schedule of siRNA
  • Assessing siRNA pharmacodynamics in animal models  
  • Research on siRNA delivery funded by the NIH 
  • Companies involved in delivery technologies for siRNA

5. RNAi in Research  

  • Introduction  
  • Basic RNAi research
  • Antiviral role of RNAi in animal cells  
  • Combination of siRNA with green fluorescent protein
  • Detection of cancer mutations  
  • Genes and lifespan  
  • Inducible and reversible RNAi
  • Loss-of-function genetic screens
  • Nanoparticles mimic RNAi
  • Profiling small RNAs
  • RNAi for research in neuroscience
  • RNAi and environmental research
  • Small nucleolar RNAs  
  • Study of signaling pathways
  • Transgenic RNAi 
  • Use of RNAi to study insulin action
  • Applied RNAi research
  • RNAi for gene expression studies
  • Microarrays for measuring gene expression in RNAi  
  • RNAi for functional genomic analysis  
  • RNAi studies on C. elegans
  • RNAi studies on Drosophila. 
  • RNAi in planaria  
  • RNAi for regenerative medicine  
  • Testing the specificity of RNAi
  • Tissue-specific RNAi
  • siRNA-mediated gene silencing  
  • RNAi libraries  
  • Enzymatic production of RNAi library
  • Next-generation libraries for RNAi-based genome-wide screens
  • pDual library using plasmid vector
  • pHippy plasmid vector library
  • siRNA libraries using pRetroSuper vector
  • siRNA produced by enzymatic engineering of DNA
  • shRNA libraries
  • RNAi and alternative splicing
  • RNAi in animal development  
  • RNAi for creating transgenic animals
  • RNAi for creating models of neurological disorders  
  • Research support for RNAi in US
  • RNAi for toxicogenomics
  • Role of RNAi in the US biodefense research
  • The RNAi Consortium
  • Research support for RNAi in Europe
  • European Union for RNA Interference Technology
  • Research support of RNAi  
  • Role of RNAi in MitoCheck project  
  • RNAi Global Initiative
  • SIROCCO project

6. RNAi in drug discovery

  • Basis of RNAi for drug discovery
  • RIP-Chip for the study of RNA-protein interactions
  • RNAi for identification of genes as therapeutic targets  
  • Role of siRNAs in drug target identification  
  • Use of a genome-wide, siRNA library for drug discovery
  • RNAi as a tool for assay development
  • Targeting human kinases with an siRNAi library
  • Challenges of drug discovery with RNAi  
  • Express Track siRNA Drug Discovery Program
  • Genome-wide siRNA screens in mammalian cells
  • PhenomicID™
  • Natural antisense and ncRNA as drug targets  
  • RNAi for target validation  
  • Delivering siRNA for target validation in vivo  
  • Validation of oncology targets discovered through RNAi screens
  • Selection of siRNA versus shRNA for target validation  
  • Off-target effects of siRNA-mediated gene silencing
  • Bioinformatic approach to off-target effects
  • siPools for eliminating off-target effects of siRNAs
  • Unlocked Nucleomonomer Agent
  • Managing off-target effects of vector-encoded shRNAs
  • Application of RNAi to the druggable genome  
  • Application of siRNA during preclinical drug development  
  • siRNAs vs small molecules as drugs
  • siRNAs vs antisense drugs
  • Chemical modifications for improving siRNA drugs
  • RNAi technology in plants for drug discovery and development  
  • Application of RNAi to poppy plant as a source of new drugs

7. Therapeutic applications of RNAi  

  • Introduction  
  • Potential of RNAi-based therapies
  • In vitro applications of siRNA
  • In vivo applications of RNAi
  • RNAi and cell therapy
  • Gene inactivation to study hESCs
  • RNAi and stem cells
  • RNAi for study of ESCs
  • RNAi and iPSCs
  • Cell therapy for immune disorders
  • RNAi gene therapy
  • Drug-inducible systems for control of gene expression  
  • Potential side effects of RNAi gene therapy 
  • Systemic delivery of siRNAs  
  • In vivo RNAi therapeutic efficacy in animal models of human diseases
  • Role of RNAi in regenerative medicine
  • Virus infections  
  • RNAi screens of viral genomes
  • RNAi approaches to viral infections.
  • Delivery of siRNAs in viral infections
  • Viral vectors for RNAi-based antiviral therapy  
  • Promise and pitfalls of RNAi gene therapy
  • RNAi applications in HIV
  • A multiple shRNA approach for silencing of HIV-1
  • Anti-HIV shRNA for AIDS lymphoma  
  • Aptamer-mediated delivery of anti-HIV siRNAs
  • Bispecific siRNA constructs
  • Role of the nef gene during HIV-1 infection and RNAi  
  • siRNA-directed inhibition of HIV-1 infection
  • Synergistic effect of snRNA and siRNA
  • Targeting CXCR4 with siRNAs
  • Targeting CCR5 with siRNAs
  • Concluding remarks on RNAi approach to HIV/AIDS
  • Influenza
  • Inhibition of influenza virus by siRNAs
  • Delivery of siRNA in influenza
  • Challenges and future prospects of siRNAs for influenza
  • Respiratory syncytial and parainfluenza viruses
  • Coronavirus/severe acute respiratory syndrome  
  • Gene editing with for COVID-19 by RNA-targeting CRISPR systems
  • mRNA vaccines for COVID-19
  • Herpes simplex virus 2
  • Hepatitis B  
  • Hepatitis C virus  
  • Cytomegalovirus  
  • Virus causing hemorrhagic fever
  • Dengue fever 
  • Antivirals in development
  • Ebola virus
  • Marburg virus
  • siRNA vs antisense oligonucleotides for viral infections
  • siRNA against methicillin-resistant S. aureus
  • RNAi-based rational approach to antimalarial drug discovery
  • Inhibiting the growth of malarial parasite by heme-binding DNA aptamers  
  • siRNA-based antimalarial therapeutics
  • RNAi applications in oncology
  • Allele-specific inhibition
  • Drug delivery issues in managing cancer by RNAi approach
  • Inhibition of oncogenes
  • Modification of alternative splicing in cancer
  • Onconase
  • Overcoming drug resistance in cancer
  • Targeting fusion proteins in cancer
  • Increasing chemosensitivity by RNAi
  • RNAi approach to study TRAIL
  • RNAi-based logic circuit for identification of specific cancer cells.
  • shRNA-based autologous cancer vaccine
  • siRNAs for anticancer drug discovery  
  • siRNAs based on huntingtin trinucleotide repeats as anticancer reagents
  • siRNAs for inducing cancer immunity  
  • siRNAs for inhibition of angiogenesis  
  • siRNA targeting the R2 subunit of ribonucleotide reductase
  • siRNA for cancer chemoprevention
  • siHybrids vs siRNAs as anticancer agents
  • Nanobiotechnology-based delivery of siRNAs
  • Lipid nanoparticle-based delivery of anticancer siRNAs
  • Minicells for targeted delivery of nanoscale anticancer therapeutics
  • Nanoimmunoliposome-based system for targeted delivery of siRNA  
  • PEG-nanoparticles for delivery of siRNA to target fusion genes 
  • Polymer nanoparticles for targeted delivery of anticancer siRNA
  • RNA nanotechnology for delivery of cancer therapeutics  
  • siRNA delivery in combination with nanochemotherapy
  • Targeted delivery of a nanoparticle-siRNA complex in cancer patients
  • Lipophilic siRNA for targeted delivery to solid tumors
  • RNAi-based treatment of various cancer types
  • RNAi-based therapy of glioblastoma multiforme  
  • RNAi in breast cancer  
  • RNAi for enhancing hyperthermia/chemotherapy in cervical cancer
  • RNAi and colorectal cancer
  • RNAi and Ewing’s sarcoma
  • RNAi and leukemias
  • RNAi and lung cancer  
  • RNAi and melanoma
  • RNAi and pancreatic cancer  
  • RNAi and prostate cancer
  • Genetic disorders
  • Acute intermittent porphyria
  • Hereditary transthyretin-mediated amyloidosis
  • Primary hyperoxaluria type 1
  • RNAi for skin disorders  
  • Experimental studies for RNAi applications in skin disorders  
  • Clinical applications of RNAi in skin disorders
  • Pachyonychia congenita
  • Neurological disorders
  • RNAi for neurodegenerative disorders
  • RNAi for limiting protein aggregation in neurodegenerative diseases
  • Alzheimer's disease
  • Parkinson's disease
  • Amyotrophic lateral sclerosis
  • Prion diseases
  • Polyglutamine-induced neurodegeneration  
  • Fragile X syndrome and RNAi
  • RNAi-based therapy for Huntington's disease  
  • Combination of RNAi and gene therapy to prevent neurodegenerative disease
  • Role of RNAi in pain therapy  
  • Role of RNAi in repair of spinal cord injury  
  • Role of RNAi in treatment of multiple sclerosis
  • siRNA for Duchenne muscular dystrophy
  • siRNA for dystonia
  • RNAi in ophthalmology  
  • Age related macular degeneration  
  • Current treatment of AMD
  • RNAi-based treatments for AMD
  • Diabetic retinopathy
  • Retinitis pigmentosa
  • RNAi and metabolic disorders
  • RNAi and obesity
  • Genes and regulation of body fat  
  • RNAi and diabetes
  • Regulation of insulin secretion by a miRNA
  • RNAi for study of genes in animal models of diabetes  
  • RNAi for drug discovery in diabetes
  • RNAi for treating liver dysfunction in diabetes
  • siRNAs for study of glucose transporter
  • siRNAs for targeting adipose inflammation in diabetes and obesity
  • RNAi in hematology
  • Stem cell-based gene therapy and RNAi for sickle cell disease
  • Targeting of antithrombin in hemophilia with RNAi
  • RNAi and disorders of the immune system
  • siRNA applications in immunology  
  • Use of RNAi in transplantation
  • RNAi for cardiovascular disorders  
  • RNAi for atherosclerosis
  • RNAi for hypercholesterolemia
  • siRNAs targeting PCSK9
  • siRNA targeting NADPH oxidase in cardiovascular diseases
  • Role of lncRNA in cardiovascular disorders  
  • siRNA for study and treatment of ischemia-reperfusion injury  
  • RNAi in respiratory disorders
  • siRNA for cystic fibrosis
  • siRNA for asthma
  • RNAi for musculoskeletal disorders
  • RNAi for rheumatoid arthritis
  • RNAi for bone disorders
  • RNAi for treatment of osteoporosis
  • RNAi for miscellaneous disorders
  • RNAi for transthyretin amyloidosis
  • Antisense for transthyretin amyloidosis  
  • Clinical trials of RNAi-based therapies
  • Improving efficacy of siRNAs for clinical trials by improved delivery
  • Role of RNAi in development of personalized medicine  
  • Future of RNAi
  • Challenges for the development of RNAi-based therapeutics  

8. Safety, regulatory and patent issues

  • Introduction  
  • Limitations and drawbacks of RNAi
  • Adverse effects of RNAi
  • Effect of siRNAs on interferon response  
  • Detection of interferon response
  • Prevention of the interferon response in RNAi  
  • Overcoming the innate immune response to siRNAs
  • Toxicity associated with RNAi
  • Selection of siRNAs to improve specificity and efficacy 
  • Regulatory issues relevant to RNAi
  • RNAi patents  
  • Companies with a strong patent position
  • Alnylam
  • Benitec  
  • Intradigm  
  • Quark Pharmaceuticals
  • Sirna Therapeutics  

9. Markets for RNAi Technologies

  • Introduction  
  • Current and future market potential for RNAi technologies
  • RNAi reagents
  • siRNA markets
  • miRNA markets
  • RNAi-based drug discovery and target validation
  • RNAi-based therapeutics
  • RNAi market potential according to therapeutic areas
  • Market for viral infections
  • Market for cancer
  • Market for age related macular degeneration
  • Unmet needs in RNAi
  • Strategies for marketing RNAi
  • Choosing optimal indications
  • Strategies according to the trends in healthcare in the next decade
  • Concluding remarks

10. Companies involved in RNAi Technologies

  • Introduction  
  • Top players in RNAi
  • Profiles of companies
  • Collaborations

11. References

Table 1-1: Various types of RNA
Table 1-2: Classification of small RNA molecules
Table 1-3: Mechanisms of small RNAs involved in gene silencing
Table 1-4: Historical landmarks in the evolution of RNAi
Table 2-1: RNAi versus small molecules
Table 2-2: Providers of software for siRNA design
Table 2-3: Methods for the production of siRNAs
Table 2-4: Advantages and limitations of methods of shRNA-derived siRNA knockdown
Table 2-5: Comparison of eiRNA with siRNA
Table 3-1: Methods for miRNA target prediction
Table 3-2: miRNA expression in neurodegenerative diseases
Table 3-3: Dysregulation of miRNA expression in epithelial cancers
Table 3-4: Delivery strategies for miRNA inhibition therapies in cancer
Table 3-5: Delivery strategies for miRNA replacement to inhibit cancer growth
Table 3-6: MiRNAs and key molecules in signaling pathways in glioblastoma
Table 3-7: Companies involved in miRNA diagnostics and therapeutics
Table 3-8: Status of therapeutic development of miRNAs
Table 4-1: Methods of delivery of oligonucleotides
Table 4-2: Methods of delivery of siRNA
Table 4-3: Companies developing siRNA delivery technologies
Table 5-1: RNAi libraries
Table 6-1: Delivery of siRNAs in vivo for target validation
Table 6-2: Selection of siRNA versus shRNA for target validation
Table 7-1: RNAi-based therapeutic approaches
Table 7-2: In vivo RNAi therapeutic efficacy in animal models of human diseases
Table 7-3: Inhibition of viral replication by RNAi
Table 7-4: Cancer-associated genes that can be targeted by RNAi
Table 7-5: Neurological disorders that have been studied by using RNAi
Table 7-6: Clinical trials of RNAi-based therapeutics
Table 9-1: RNAi markets according to technologies and reagents 2020-2030
Table 9-2: Markets for RNAi therapy for selected diseases: years 2020-2030
Table 10-1: RNAi reagent, technology and service companies
Table 10-2: Pharmaceutical companies using RNAi for drug discovery and development
Table 10-3: Biotechnology companies using RNAi for drug discovery and development
Table 10-4: Companies developing RNAi-based therapeutic products
Table 10-5: Ten top players in RNAi
Table 10-6: Proprietary reagents of ImuThes
Table 10-7: Product pipeline of Silence Therapeutics
Table 10-8: Collaborations in RNAi technologies

Figure 1-1: Relationship of DNA, RNA and protein in the cell
Figure 1-2: tsRNAs in a model of hepatocellular carcinoma
Figure 1-3: Schematic of suppression of gene expression by RNAi
Figure 1-4: Relation of RNAi to epigenetic mechanisms
Figure 2-1: Overview of ShortCut RNAi Kit
Figure 2-2: Gene silencing by RNAi induced with ddRNAi
Figure 2-3: saRNA for targeted gene activation
Figure 3-1: A schematic miRNA pathway with points of action of miRNA tools
Figure 3-2: Molecular mechanisms of miRNA generation
Figure 3-3: miRNA alternations in neurodegenerative diseases
Figure 3-4: Multiple targets of miRNAs
Figure 4-1: RNA aptamer-mediated targeted RNAi delivery in cancer therapy
Figure 7-1: Targeting disease by RNAi
Figure 7-2: Identification of protein targets in neurodegenerative disorders
Figure 7-3: Mechanism of action of inclisiran
Figure 7-4: Role of RNAi in personalized medicine
Figure 8-1: Problems with use of synthetic siRNAs and measures to prevent them
Figure 9-1: Unmet needs in RNAi technologies

Companies Mentioned

  • Alnylam
  • Benitec
  • Intradigm
  • Quark Pharmaceuticals
  • Sirna Therapeutics