Home > Back to Publisher > Report Information
Antisense Therapy: Technical Aspects and Commercial OpportunitiesBusiness InsightsMarch 1, 2000 336 Pages - SKU: RET86 |
|
- Executive Summary
- Chapter 1 Introduction to Antisense Therapeutics
- Definitions
- Historical evolution
- Basics of antisense therapy
- Gene regulation
- Naturally occurring antisense RNA
- Antisense approaches
- Antisense RNA and DNA
- Mechanism of antisense oligonucleotide inhibition
- Antisense RNA vs. antisense oligonucleotides
- Role of antisense in clinical medicine
- Human diseases due to disturbances of mRNA
- RNA mutations
- Non-coding RNAs
- RNA triple repeats
- Nonsense-mediated mRNA decay
- Potential clinical applications of antisense therapy
- Advantages of antisense approach over conventional pharmacotherapy
- Limitations of antisense therapy
- Non-clinical applications of antisense technologies
- The role of antisense technologies in the biopharmaceutical industry
- Antisense versus traditional drug development
- Role of antisense in the bioprocessing industry
- Chapter 2 Chemistry and Pharmacology Of Antisense Oligonucleotides
- Chemistry
- Oligonucleotide structure
- RNA structure
- Synthesis, purification, and analysis of oligonucleotides
- First generation oligonucleotides
- Pharmacology
- Pharmacokinetics
- Entry and distribution of oligonucleotides into cells
- Mechanisms of action of antisense drugs
- Inhibition of mRNA translation
- Activation of ribonucleases H (RNases H)
- Proof of mechanism
- Non-specific and non-antisense effects
- Pharmacological basis of applications of antisense oligonucleotides
- Chapter 3 Antisense Technologies
- Introduction
- Techniques of delivery of oligonucleotides to the body tissues
- Routes of administration
- Gastrointestinal tract-oral and rectal
- Iontophoretic delivery into subcutaneous tumors
- Local application
- Pulmonary administration
- Targeted delivery to the arteries
- Pressure-mediated transfer to arterial wall
- Microbubble contrast agent
- Targeted delivery to brain cells
- Delivery across the BBB
- High flow microinfusion into the brain parenchyma
- Intracerebroventricular administration using Alzet Osmotic Pumps
- Intracellular guidance by special techniques
- Biochemical microinjection
- Receptor-mediated endocytosis
- Liposomes-mediated oligonucleotide delivery
- Polyethylenimine-mediated oligonucleotide delivery
- Terplex-mediated oligonucleotide delivery
- Use of histidylated oligolysines to facilitate cytosolic delivery of antisense
- oligonucleotides
- Biodegradable microparticles
- Electroporation
- Ex vivo approach
- Delivery of oligonucleotides: summary
- Antisense drug design
- Selection of optimal oligonucleotide targets
- Second generation oligonucleotides
- Third generation oligonucleotides
- Incorporation of 2'-O-(2-methoxy)ethyl chemistry
- Cytosine analogues
- Phenoxazine-modified oligonucleotides
- Morpholino-type oligonucleotides
- Peptide nucleic acid (PNA)
- PNA structure
- Biological activity of PNA
- Systemic administration of peptide nucleic acids (PNAs)
- PNAs versus oligonucleotides
- PNA-DNA chimeras
- Applications of PNA technology
- Locked nucleic acid (LNA)
- Structure
- Biological activity
- Applications
- RNA Therapeutics
- RNA as a drug target
- Sense RNA versus plasmid DNA
- Antisense RNA molecules
- Chimeras in antisense therapy
- Chimeric oligonucleotides
- Chimeric 2-5A antisense molecules
- RNA-DNA chimeras/chimeraplasty
- Aptamers
- Structure
- RNA and DNA aptamers
- Clinical applications
- Assessment of antisense effects
- The ideal antisense oligonucleotide
- Development of cost-effective oligonucleotides
- Antisense oligonucleotides for functional genomics and drug target validation
- Antisense oligonucleotides in a high-throughput approach for target validation
- Technical approach to RNA as drug target
- PNA antisense for target validation
- Antisense oligonucleotides and molecular diagnostics
- Use of antisense approaches for diagnostics
- Molecular diagnostic technologies for monitoring antisense oligonucleotide action
- Antisense gene therapy
- Antisense RNA using vectors
- Single strand (ss) DNA oligonucleotide mediated antisense
- Insertion of a gene that will produce specific antisense nucleic acids in cells
- Decoy oligodeoxynucleotides
- Antisense technologies for basic research in neurobiology
- Inhibition of neurotransmitters using antisense oligonucleotides
- Antisense technology for study of immediate-early response genes in the CNS
- Antisense transgenesis
- Patenting of antisense technologies
- Basics of antisense patenting
- What is patentable in antisense technology?
- Patenting strategies
- Patenting activities and positions
- Chapter 4 Clinical Applications Of Antisense Pharmaceuticals
- Introduction
- Inflammatory processes
- Pathomechanism in relation to antisense oligonucleotide action
- Intercellular adhesion molecule 1
- Antisense phosphorothioate oligonucleotide to p65 subunit of NF-?B
- Use of antisense oligonucleotides in inflammatory diseases
- Crohn's disease
- Asthma
- Cancer
- Antisense targets related to solid tumors
- Use of antisense oligonucleotides for inhibiting oncogenes
- Inhibition of tumor growth by targeting antisense oligonucleotide to cell signaling
- Antisense oligonucleotides targeted to growth factors
- Antisense oligonucleotides targeted to matrix metalloprotease
- Inhibition of fusion genes by antisense oligonucleotides
- Inhibition of lipoxygenase
- Targeting DNA methyltransferase
- Telomerase inhibitors
- Induction of apoptosis
- Radiosensitizing effect of antisense oligonucleotides
- Combination of antisense and chemotherapy
- Antisense oligonucleotides against multidrug resistance
- Antisense targets related to type and location of malignancy
- Antisense oligonucleotides for leukemia
- Antisense oligonucleotides for lymphoma
- Brain tumors
- Antisense therapy of prostate cancer
- Antisense therapy of non-small cell lung cancer
- Antisense clinical trials for cancer
- Future prospects of antisense oligonucleotides in cancer therapy
- Antisense oligonucleotides for virus infections
- Antisense oligonucleotides for HIV-1 infection
- Antisense approach to hepatitis viruses
- Hepatitis B virus (HBV)
- Hepatitis C virus (HCV)
- Hepatitis Delta virus (HDV)
- Antisense approach to respiratory syncytial virus
- Recently introduced/clinical trials of antisense oligonucleotides for viral infections
- Fomivirsen for CMV retinitis
- Antisense oligonucleotides for protozoal infections
- Malaria
- Leishmaniasis
- Trypanosomiasis
- Antisense oligonucleotides for cardiovascular diseases
- Hypertension
- Prevention of restenosis after angioplasty
- Pathomechanism of restenosis after angioplasty
- Antisense approaches for prevention of restenosis after angioplasty
- Methods of delivery of antisense oligonucleotides to the site of restenosis
- Prevention of atherosclerosis in vascular grafts
- Prevention of arterial thrombus formation
- Antisense oligonucleotides for neurological disorders
- Neurodegenerative disorders
- Cerebrovascular disease
- Use of antisense approach in neurotransmitter regulation
- Drug abuse
- Neuropsychiatric disorders
- Antisense approach to anxiety disorders
- Antisense oligonucleotides in renal disease
- Future prospects of antisense oligonucleotides
- Chapter 5 Triple Helix Oligonucleotides
- Molecular structure of triplex oligonucleotides
- Mechanism of action
- Cellular delivery
- Triplex drug design
- Potential clinical applications of triplex oligonucleotides
- Viral infections
- Cancer
- Genetic diseases
- Future prospects of triple helix compounds
- Chapter 6 Ribozymes
- Introduction
- Molecular structure
- RNase P
- Hairpin ribozyme
- Hammerhead ribozymes
- Ribozyme motif in HDV
- Deoxyribozymes (DNAzymes)
- Mechanism of action of ribozymes
- Methods of delivery/ ribozyme gene therapy
- Potential clinical applications
- Potential of ribozymes as antiviral agents
- Ribozymes as anti-HIV therapy
- Influenza A virus
- Hepatitis viruses
- Applications in cancer
- Ribozyme approach for carcinoma of the bladder
- Ribozymes for treatment of human pancreatic carcinoma
- Ribozyme for lung cancer
- Ribozyme for breast cancer
- Ribozyme approach for malignant melanoma
- Ribozyme approach for chronic myelogenous leukemia
- Ribozymes and multidrug resistance
- Concluding remarks on the application of ribozymes in cancer
- Treatment of restenosis following angioplasty
- Potential applications of ribozymes in genetic disorders
- Miscellaneous applications of ribozymes
- Ribozymes in clinical development
- Current status and future of ribozymes
- Chapter 7 Toxicity and Drug Safety Issues
- Introduction
- Pathways for antisense oligonucleotide toxicity
- Sequence-dependent toxicity
- Sequence-independent toxicity
- Safety testing of antisense oligonucleotides
- Adverse effects of antisense oligonucleotides
- Adverse effects in animal experimental studies
- Adverse effects in clinical trials in humans
- Immunological adverse effects
- Cardiac adverse effects
- Hematological adverse effects
- Genotoxicity of antisense oligonucleotides
- Summary of toxicity and drug safety issues
- Chapter 8 Regulatory Aspects Of Antisense Oligonucleotides
- Introduction
- Preclinical studies of antisense oligonucleotides
- Regulatory issues concerning the chemistry of oligonucleotides
- Structure
- Purity
- Stability
- Regulatory issues concerning the pharmacology of oligonucleotides
- Regulatory issues concerning toxicology studies of oligonucleotides
- Intravenous administration of phosphorothioates
- Special considerations for toxicology studies of oligonucleotides
- Targets
- Oligonucleotides acting at protein sites
- Delivery
- Special toxicity
- Cellular toxicity
- Pharmacokinetic studies
- Ex vivo antisense therapy
- General recommendations
- Regulatory requirement for submission of an IND
- General requirements
- Special requirements for antisense oligonucleotides
- Identity and characteristics
- Reagents
- Manufacturing process
- Test methods
- Stability
- Clinical trials with antisense oligonucleotides
- Introduction
- Phase I
- Phases II and III
- NDA (New Drug Application)
- Clinical trials according to indication
- Special requirements for clinical trials in cancer
- Special requirements for clinical trials in HIV-related diseases
- Clinical trials of antisense approach to prevention of restenosis
- Chapter 9 Commercial Aspects Of Antisense Therapy
- Introduction
- The cost of antisense drug development
- Market value of antisense technology
- An approach to the calculation of potential markets for antisense therapy
- Calculation of markets according to type of antisense technology
- Antisense oligonucleotides
- Ribozymes
- Locked nucleic acid (LNA)
- Peptide nucleic acid (PNA)
- Antisense diagnostics
- Antisense drug discovery
- Biopharmaceutical processing industry
- Calculation of markets according to therapeutic areas
- HIV-1/AIDS
- Genital warts/human papilloma virus (HPV)
- Cytomegalovirus (CMV)
- HBV
- HCV
- Influenza
- Miscellaneous infections including protozoal infections
- Cancer
- Prevention of coronary restenosis after angioplasty
- Rheumatoid arthritis
- Crohn's disease
- Calculation of markets according to geographical areas
- Commercial opportunities in antisense technologies
- Marketing strategies
- View of the regulatory authorities
- Development of competing technologies
- Special requirements for manufacturing process of oligonucleotides
- General strategies for marketing antisense drugs
- Choosing of optimal indications
- Partnership between antisense companies and large pharmaceutical companies
- Reduction of manufacturing costs
- Strategies according to the trends in healthcare in the 21st century
- Physician education
- Public education
- Diseases
- Drugs
- Combination of diagnostics and therapeutics
- Healthcare companies
- Prevention
- Unmet needs in antisense therapeutics
- Summary of financial aspects of antisense therapy
- Chapter 10 Companies Active In Development Of Antisense Products
- Introduction
- Pharmaceutical companies active in antisense therapy
- Antisense company profiles
- Aronex Pharmaceuticals Inc
- Corporate overview
- Products
- Atlantic Pharmaceuticals Inc
- Corporate overview
- Antisense technology
- Products/applications
- Atugen Biotechnology AG
- Corporate overview
- Antisense technology
- Services
- Collaborations
- AVI Biopharma Inc
- Corporate overview
- Antisense technology
- Product pipeline
- Research grants
- Collaborations
- Patents
- Biognostik AG
- Corporate overview
- Products
- BioSource International Inc
- Corporate overview
- Boron Biologicals Inc
- Corporate overview
- Antisense technology
- Cryogenic Solutions
- Corporate overview
- Antisense technology/applications
- Patents and intellectual property
- Collaborations
- Independent research studies
- Enzo Therapeutic Inc
- Corporate overview
- Antisense technology/products
- Patents
- Epigenesis Pharmaceuticals
- Corporate overview
- Financials
- Antisense technology
- Products
- Epoch Pharmaceuticals
- Corporate overview
- Financials
- Antisense technology
- Applications
- Patents
- Collaborations
- Exiqon AG
- Corporate overview
- Collaborations
- Antisense technology/products
- Gene Tools LLC
- Corporate overview
- Products
- Genta Inc
- Corporate overview
- Financials
- Antisense technology
- Products
- Collaborations
- Geron Inc
- Corporate overview
- Financials
- Antisense technology
- Gilead Sciences
- Corporate overview
- Financials
- Product pipeline
- Collaborations
- Hybridon Inc
- Corporate overview
- Financials
- Antisense technology
- Patents/licensing/intellectual property 2
- Product pipeline
- Collaborations
- Ibis Therapeutic
- Corporate overview
- Antisense technology
- Product pipeline
- Collaborations
- Immusol Inc
- Corporate overview
- Antisense technology
- Products
- Collaborations
- Patents
- Integrated DNA Technologies (IDT)
- Corporate overview
- Antisense technology/services
- Collaborations
- Patents
- Inex Pharmaceuticals Corporation
- Corporate overview
- Financials
- Antisense technology
- Products
- Patents
- Collaborations
- Isis Pharmaceuticals
- Corporate overview
- Financials
- Antisense technology
- Product pipeline
- Collaborations
- Patents
- Kimeragen Inc
- Corporate overview
- Financials
- Antisense technology
- Collaborations
- Potential applications
- Lorus Therapeutics
- Corporate overview
- Financials
- Antisense technology
- Product pipeline
- MethylGene Inc
- Corporate overview
- Financials
- Antisense technology
- Product pipeline
- Collaborations
- NeoPharm Inc
- Corporate overview
- Products
- Collaborations
- Patents
- Oligo Therapeutics Inc
- Corporate overview
- Antisense technology
- Patents
- OriGenix Technologies
- Corporate overview
- Financials
- Antisense technology/product pipeline
- Pantheco AG
- Corporate overview
- Financials
- Antisense technology/applications
- Ribotargets Ltd
- Corporate overview
- Financials
- Antisense technology
- Product pipeline
- Ribozyme Pharmaceuticals
- Corporate overview
- Financials
- Antisense technology
- Patents/licenses
- Product pipeline
- Collaborations
- Salus Therapeutics Inc
- Corporate overview
- Antisense technology
- Applications
- Research grants
- Sequitur Inc
- Corporate overview
- Antisense technology
- Services
- Collaborations
- Patents
- Trilink Biotechnologies Inc
- Corporate overview
- Chapter 11 Appendix
- Abbreviations
- Glossary
- References
- List of Figures
- Figure 1.1: Regulatory processes in the normal cell
- Figure 1.2: Antisense strategies
- Figure 1.3: Potential clinical applications of antisense therapy
- Figure 1.4: Relation of antisense technologies to other segments of
- biopharmaceutical industry
- Figure 2.5: Structural formulae of oligonucleotide analogues
- Figure 3.6: Mechanism of action of peptide nucleic acid (PNA)
- Figure 5.7: The triple helix forming oligonucleotide (shown in bold) binds to the
- double helix of the DNA target
- Figure 5.8: Proposed mechanism of action of triplex-forming oligonucleotides
- Figure 6.9: Mechanism of control of viral replication by ribozymes
- Figure 9.10: Forecast total value of the global antisense market, 2000-2010
- Figure 9.11: Unfulfilled potential in antisense therapeutics
- List of Tables
- Table 1.1: Historical landmarks in the development of antisense therapeutics
- Table 1.2: Molecular basis of antisense therapeutics
- Table 2.3: Molecular mechanisms of action of antisense drugs
- Table 3.4: Methods of administration of oligonucleotides
- Table 3.5: Antisense technologies as gene therapy approaches
- Table 3.6: Potential applications of vectors expressing antisense RNA
- Table 4.7: Mechanisms of anti-cancer effect of antisense oligonucleotides
- Table 4.8: Antisense oligonucleotides targeted to oncogenes in solid tumors
- Table 4.9: Antisense therapies in development for glioblastoma multiforme
- Table 4.10: Antisense oligonucleotides in clinical trials for cancer
- Table 4.11: Viruses amenable to antisense therapy in vitro
- Table 4.12: Antisense oligonucleotides for viral infections: clinical trials/approved
- Table 6.13: Ribozymes in clinical development
- Table 9.14: Current market value of selected therapeutic areas relevant to antisense therapy
- Table 9.15: Market size according to type of antisense technologies and their applications
- Table 9.16: Markets for antisense therapy for selected indications, 2000-2010
- Table 9.17: Market size according to type of antisense technologies and their applications
- Table 10.18: Classification of antisense companies
- Table 10.19: Pharmaceutical companies active in the antisense therapy sector
- Table 10.20: Isis' product pipeline, 1999
- Table 10.21: MethylGene's R&D pipeline, 1999
- Table 10.22: NeoPharm antineoplastic products in development
Related Markets
Genetic Engineering Reports
- Genetic Engineering
- Stem Cell Markets
- Patent map and technology intelligence report. Micro-organisms/Enzymes; Propagating, Preserving Or Maintaining Micro-organisms; Genetic Engineering; Culture Media
- The World Market for Biosimilars and the Potential for US Follow-on Biologics
- Stem Cell Technology: Current Applications and Future Directions